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- #607014 - HURLER SYNDROME
- OMIM
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<span class="h4">#607014</span>
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/607014"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS607014"> <strong>Phenotypic Series</strong> </a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#nomenclature">Nomenclature</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#clinicalFeatures">Clinical Features</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#biochemicalFeatures">Biochemical Features</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#diagnosis">Diagnosis</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#clinicalManagement">Clinical Management</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#populationGenetics">Population Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#history">History</a>
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<a href="#seeAlso"><strong>See Also</strong></a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=HURLER SYNDROME" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=132&Typ=Pat" title="Mucopolysaccharidosis type 1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Mucopolysaccharidosis type…&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=12381&Typ=Pat" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Hurler syndrome&nbsp;</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1162/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://www.acmg.net/PDFLibrary/MPSI-ACT-Sheet.pdf" class="mim-tip-hint" title="Information and resources for newborn screening and genetics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Newborn Screening', 'domain': 'www.acmg.net'})">Newborn Screening</a></div>
<div><a href="#mimOrphanetFold" id="mimOrphanetToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="European reference portal for information on rare diseases and orphan drugs."><span id="mimOrphanetToggleTriangle" class="small" style="margin-left: -0.8em;">&#9658;</span>Orphanet</div>
<div id="mimOrphanetFold" class="collapse">
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=579" title="Mucopolysaccharidosis type 1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Mucopolysaccharidosis type…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=93473" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Hurler syndrome</a></div>
</div>
<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/af5118f1-f02d-4544-84ab-ebf9f5a8a6d2/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
<span class="panel-title">
<span class="small">
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Animal Models</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.alliancegenome.org/disease/DOID:0111390" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
<div><a href="http://www.informatics.jax.org/disease/607014" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
<div><a href="https://omia.org/OMIA000664/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
<span class="panel-title">
<span class="small">
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Cell Lines</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:607014" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
</div>
</div>
</div>
</div>
</div>
</div>
<span>
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
&nbsp;
</span>
</span>
</div>
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>SNOMEDCT:</strong> 65327002<br />
<strong>ICD10CM:</strong> E76.01<br />
<strong>ORPHA:</strong> 579, 93473<br />
<strong>DO:</strong> 0111390<br />
">ICD+</a>
</div>
<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
607014
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
HURLER SYNDROME
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<a id="alternativeTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
MUCOPOLYSACCHARIDOSIS TYPE IH; MPS1-H
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/22?start=-3&limit=10&highlight=22">
4p16.3
</a>
</span>
</td>
<td>
<span class="mim-font">
Mucopolysaccharidosis Ih
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607014"> 607014 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
IDUA
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252800"> 252800 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/607014" class="btn btn-warning" role="button"> Clinical Synopsis </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
</button>
</div>
&nbsp;
<div class="btn-group">
<a href="/phenotypicSeries/PS607014" class="btn btn-info" role="button"> Phenotypic Series </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
</button>
</div>
&nbsp;
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
</button>
<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/607014" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/607014" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
</ul>
</div>
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GROWTH </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Height </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Short stature <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422065006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422065006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237836003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237836003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237837007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237837007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E34.31" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E34.31</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R62.52" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R62.52</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.43" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.43</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0349588&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0349588</a>, <a href="https://bioportal.bioontology.org/search?q=C0013336&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013336</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003510</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Head </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Macrocephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/12138000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">12138000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1145403003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1145403003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q75.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q75.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221355&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221355</a>, <a href="https://bioportal.bioontology.org/search?q=C2243051&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2243051</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000256" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000256</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001355" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001355</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000256" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000256</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=dd989bb153739761147ef05dc870b050" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Macrocephaly-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=dd989bb153739761147ef05dc870b050&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Face </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Coarse face <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1845847&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1845847</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000280</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000280</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=cda94218d725bd8a9c75ca88c2113224" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Face,Coarse-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=cda94218d725bd8a9c75ca88c2113224&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Full cheeks <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1866231&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1866231</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000293" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000293</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000293" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000293</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=85459d10e5df48479ec4a2ec6cfc0455" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Cheeks,Full-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=85459d10e5df48479ec4a2ec6cfc0455&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Ears </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hearing loss (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/103276001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">103276001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/343087000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">343087000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/15188001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">15188001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H91.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H91.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/389.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.9</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/389" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011053&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011053</a>, <a href="https://bioportal.bioontology.org/search?q=C0018772&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018772</a>, <a href="https://bioportal.bioontology.org/search?q=C1384666&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1384666</a>, <a href="https://bioportal.bioontology.org/search?q=C3887873&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3887873</a>, <a href="https://bioportal.bioontology.org/search?q=C2029884&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2029884</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000365" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000365</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000365" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000365</a>]</span><br /> -
Recurrent ear infections <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0743360&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0743360</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0410018" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0410018</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0410018" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0410018</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Cloudy corneas <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1856661&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1856661</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007759" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007759</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007759" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007759</a>]</span><br /> -
Glaucoma (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/23986001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">23986001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H40-H42" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H40-H42</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H40</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H40.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H40.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/365" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">365</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/365.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">365.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0017601&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0017601</a>, <a href="https://bioportal.bioontology.org/search?q=C0997768&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0997768</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000501" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000501</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000501" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000501</a>]</span><br /> -
Retinal degeneration (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95695004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95695004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0035304&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0035304</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000546" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000546</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000546" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000546</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Nose </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Low nasal bridge <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836542&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836542</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005280</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005280</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=7043769fd21a78a413fd758918cdda17" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Nasal_Bridge,Depressed-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=7043769fd21a78a413fd758918cdda17&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Anteverted nostrils <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/708670007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">708670007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1840077&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1840077</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000463" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000463</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000463" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000463</a>]</span><br /> -
Broad nasal tip <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249327002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249327002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0426429&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0426429</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000455" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000455</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000455" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000455</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=6ddac380d031baefd82dea5c5d13ca2a" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Nasal_Tip,Broad-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=6ddac380d031baefd82dea5c5d13ca2a&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Mouth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Full lips <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248177001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248177001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836543&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836543</a>, <a href="https://bioportal.bioontology.org/search?q=C0424485&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424485</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012471" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012471</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012471" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012471</a>]</span><br /> -
Gum hypertrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/441787004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">441787004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0017567&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0017567</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000212" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000212</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000212" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000212</a>]</span><br /> -
Enlarged tongue <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/25273001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">25273001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/270516002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">270516002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K14.8" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K14.8</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q38.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q38.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/750.15" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">750.15</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0024421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0024421</a>, <a href="https://bioportal.bioontology.org/search?q=C0009677&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009677</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000158" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000158</a>]</span><br /> -
Hypertrophy of alveolar ridge <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1856164&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1856164</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009085" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009085</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Teeth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Small teeth <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/32337007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">32337007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K00.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K00.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240340&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240340</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000691" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000691</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000691" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000691</a>]</span><br /> -
Misaligned teeth <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3277349&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3277349</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Neck </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Short neck <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95427009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95427009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0521525&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0521525</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000470" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000470</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000470" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000470</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=5edf45ce6835f32360d28d26249e2531" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Neck,Short-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=5edf45ce6835f32360d28d26249e2531&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> CARDIOVASCULAR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Heart </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Endocardial fibroelastosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/65457005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">65457005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I42.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/425.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">425.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0014117&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0014117</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001706" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001706</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001706" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001706</a>]</span><br /> -
Cardiomyopathy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/85898001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">85898001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/57809008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">57809008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I51.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I51.5</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/I42" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/I42.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/425" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">425</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0878544&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0878544</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001638" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001638</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001638" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001638</a>]</span><br /> -
Aortic regurgitation (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/60234000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">60234000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0003504&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0003504</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001659" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001659</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001659" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001659</a>]</span><br /> -
Mitral regurgitation (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/48724000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">48724000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026266&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026266</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001653" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001653</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001653" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001653</a>]</span><br /> -
Mitral valve thickening <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/448820003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">448820003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3164530&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3164530</a>]</span><br /> -
Aortic valve thickening <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0741190&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0741190</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Vascular </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Narrow coronary arteries <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/233970002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">233970002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0242231&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0242231</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005145" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005145</a>]</span><br /> -
Thickened coronary arteries <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3807612&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3807612</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> RESPIRATORY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Frequent upper and lower respiratory tract infections <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3807607&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3807607</a>]</span><br />
</span>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Nasopharynx </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Enlarged tonsils <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/46689006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">46689006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/301471002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">301471002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249395001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249395001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/J35.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">J35.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0549123&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0549123</a>, <a href="https://bioportal.bioontology.org/search?q=C0272386&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0272386</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030812</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030812</a>]</span><br /> -
Enlarged adenoids <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3807608&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3807608</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Larynx </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Enlarged vocal cords <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3807609&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3807609</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Airways </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Narrow trachea <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/11296007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">11296007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0040583&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0040583</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002777" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002777</a>]</span><br /> -
Thickened mainstem bronchi <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3807610&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3807610</a>]</span><br /> -
Chronic obstructive airway disease <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/13645005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">13645005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/J44.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">J44.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0024117&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0024117</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006510</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> CHEST </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Ribs Sternum Clavicles & Scapulae </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Oar-shaped ribs (narrow at vertebral end, broad at sternal end) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3807600&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3807600</a>]</span><br /> -
Short, thick, irregular clavicles <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3807601&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3807601</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ABDOMEN </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> External Features </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Umbilical hernia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/396347007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">396347007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K42" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K42</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K42.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K42.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/553.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">553.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019322&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019322</a>, <a href="https://bioportal.bioontology.org/search?q=C0041636&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0041636</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001537" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001537</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001537" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001537</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Liver </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hepatomegaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80515008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80515008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019209&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019209</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Spleen </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Splenomegaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16294009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16294009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038002&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038002</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001744" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001744</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001744" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001744</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GENITOURINARY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> External Genitalia (Male) </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Inguinal hernia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/396232000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">396232000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K40</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K40.90" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K40.90</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/550" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">550</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019294&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019294</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000023" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000023</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000023" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000023</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKELETAL </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Joint stiffness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/84445001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">84445001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0162298&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0162298</a>, <a href="https://bioportal.bioontology.org/search?q=C4085642&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4085642</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001387" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001387</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001387" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001387</a>]</span><br /> -
Joint contractures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/7890003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">7890003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M24.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M24.5</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/718.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">718.4</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/718.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">718.40</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0009918&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009918</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0034392" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0034392</a>]</span><br /> -
Dysostosis multiplex <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/254069004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">254069004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5848292&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5848292</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000943" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000943</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000943" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000943</a>]</span><br />
</span>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Skull </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Premature closure of the metopic suture <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3807602&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3807602</a>]</span><br /> -
Premature closure of the sagittal suture <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3807603&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3807603</a>]</span><br /> -
J-shaped sella turcica <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854718&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854718</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002680" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002680</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002680" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002680</a>]</span><br /> -
Hydrocephalus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/230745008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">230745008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G91" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G91</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/G91.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G91.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020255&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020255</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000238" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000238</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000238" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000238</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Spine </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Odontoid hypoplasia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1846439&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1846439</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003311" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003311</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003311" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003311</a>]</span><br /> -
Dysplastic vertebral bodies <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3807604&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3807604</a>]</span><br /> -
Gibbus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/414564002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">414564002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/413428007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">413428007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M40.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M40.20</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/737.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">737.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0022821&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022821</a>, <a href="https://bioportal.bioontology.org/search?q=C0022822&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022822</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002808" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002808</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Pelvis </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Coxa valga <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/33754009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">33754009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16979000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16979000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/299236004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">299236004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q65.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q65.81</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/755.61" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">755.61</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/736.31" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">736.31</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0158480&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0158480</a>, <a href="https://bioportal.bioontology.org/search?q=C0152430&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0152430</a>, <a href="https://bioportal.bioontology.org/search?q=C0239137&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239137</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002673" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002673</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002673" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002673</a>]</span><br /> -
Flared iliac wings <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1865841&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1865841</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002869" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002869</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002869" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002869</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Limbs </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Small femoral heads <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1856920&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1856920</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008802" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008802</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008802" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008802</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Hands </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Bullet-shaped phalanges <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3807605&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3807605</a>]</span><br /> -
Carpal tunnel syndrome <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/57406009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">57406009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G56.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G56.00</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/G56.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G56.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/354.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">354.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0007286&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007286</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012185" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012185</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012185" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012185</a>]</span><br /> -
Claw-hand deformity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/13624003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">13624003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q71.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q71.6</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q71.60" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q71.60</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/755.58" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">755.58</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2699510&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2699510</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001171" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001171</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0100257" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100257</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKIN, NAILS, & HAIR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Skin </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Dermal melanocytosis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3806322&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3806322</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Hair </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hirsutism <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/399939002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">399939002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/L68.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L68.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/704.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">704.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001007</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> NEUROLOGIC </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Central Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Developmental delay evident by 12-24 months of age <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3807598&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3807598</a>]</span><br /> -
Progressive mental deterioration <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854838&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854838</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002344" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002344</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002344" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002344</a>]</span><br /> -
Mental retardation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/228156007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">228156007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/110359009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">110359009</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/317-319.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">317-319.99</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714756&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714756</a>, <a href="https://bioportal.bioontology.org/search?q=C0025362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span><br /> -
Neurodegeneration <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0027746&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027746</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002180" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002180</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002180" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002180</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Excretion of dermatan sulfate and heparan sulfate in urine <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3807606&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3807606</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Treatment with hematopoietic stem cell transplant if diagnosed at < 24 months of age<br /> -
Enzyme replacement therapy will help visceral manifestations but cannot cross blood-brain barrier, so will not help neurodegeneration<br /> -
Alpha-L-iduronidase activity is <1% for all forms of MPS1<br /> -
MPS1 types are distinguished clinically by age of onset and progression or by mutation(s)<br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Caused by mutation in the alpha-L-iduronidase gene (IDUA, <a href="/entry/252800#0001">252800.0001</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<h5>
Mucopolysaccharidoses
- <a href="/phenotypicSeries/PS607014">PS607014</a>
- 13 Entries
</h5>
</div>
</div>
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
<table class="table table-bordered table-condensed table-hover mim-table-padding">
<thead>
<tr>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Location</strong>
</th>
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
<strong>Phenotype</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Inheritance</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />mapping key</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />MIM number</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus<br />MIM number</strong>
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/149?start=-3&limit=10&highlight=149"> 3p22.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/253010"> Mucopolysaccharidosis type IVB (Morquio) </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/253010"> 253010 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611458"> GLB1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611458"> 611458 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/337?start=-3&limit=10&highlight=337"> 3p21.31 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601492"> Mucopolysaccharidosis type IX </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/601492"> 601492 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607071"> HYAL1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607071"> 607071 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/22?start=-3&limit=10&highlight=22"> 4p16.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607016"> Mucopolysaccharidosis Is </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607016"> 607016 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252800"> IDUA </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252800"> 252800 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/22?start=-3&limit=10&highlight=22"> 4p16.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607015"> Mucopolysaccharidosis Ih/s </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607015"> 607015 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252800"> IDUA </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252800"> 252800 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/4/22?start=-3&limit=10&highlight=22"> 4p16.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607014"> Mucopolysaccharidosis Ih </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607014"> 607014 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252800"> IDUA </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252800"> 252800 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/282?start=-3&limit=10&highlight=282"> 5q14.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/253200"> Mucopolysaccharidosis type VI (Maroteaux-Lamy) </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/253200"> 253200 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611542"> ARSB </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611542"> 611542 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/330?start=-3&limit=10&highlight=330"> 5q15 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619698"> Mucopolysaccharidosis, type X </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/619698"> 619698 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610011"> ARSK </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610011"> 610011 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/297?start=-3&limit=10&highlight=297"> 7q11.21 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/253220"> Mucopolysaccharidosis VII </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/253220"> 253220 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611499"> GUSB </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611499"> 611499 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/8/244?start=-3&limit=10&highlight=244"> 8p11.21-p11.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252930"> Mucopolysaccharidosis type IIIC (Sanfilippo C) </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252930"> 252930 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610453"> HGSNAT </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610453"> 610453 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/16/739?start=-3&limit=10&highlight=739"> 16q24.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/253000"> Mucopolysaccharidosis IVA </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/253000"> 253000 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612222"> GALNS </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612222"> 612222 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/579?start=-3&limit=10&highlight=579"> 17q21.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252920"> Mucopolysaccharidosis type IIIB (Sanfilippo B) </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252920"> 252920 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609701"> NAGLU </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609701"> 609701 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/1017?start=-3&limit=10&highlight=1017"> 17q25.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252900"> Mucopolysaccharidosis type IIIA (Sanfilippo A) </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/252900"> 252900 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605270"> SGSH </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/605270"> 605270 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/X/783?start=-3&limit=10&highlight=783"> Xq28 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/309900"> Mucopolysaccharidosis II </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/309900"> 309900 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300823"> IDS </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300823"> 300823 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
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<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
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<p>A number sign (#) is used with this entry because Hurler syndrome is caused by homozygous or compound heterozygous mutation in the gene encoding alpha-L-iduronidase (IDUA; <a href="/entry/252800">252800</a>) on chromosome 4p16.</p>
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<p>The mucopolysaccharidoses are a group of inherited disorders caused by a lack of specific lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs), or mucopolysaccharides. The accumulation of partially degraded GAGs causes interference with cell, tissue, and organ function.</p><p>Deficiency of alpha-L-iduronidase can result in a wide range of phenotypic involvement with 3 major recognized clinical entities: Hurler (MPS IH), Scheie (MPS IS; <a href="/entry/607016">607016</a>), and Hurler-Scheie (MPS IH/S; <a href="/entry/607015">607015</a>) syndromes. Hurler and Scheie syndromes represent phenotypes at the severe and mild ends of the MPS I clinical spectrum, respectively, and the Hurler-Scheie syndrome is intermediate in phenotypic expression (<a href="#50" class="mim-tip-reference" title="McKusick, V. A. &lt;strong&gt;Heritable Disorders of Connective Tissue. (4th ed.)&lt;/strong&gt; St. Louis: C. V. Mosby Co. (pub.) 1972."None>McKusick, 1972</a>).</p><p>MPS I is more frequent than MPS II (Hunter syndrome; <a href="/entry/309900">309900</a>), which has no corneal clouding and pursues a slower course.</p>
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<p><a href="#48" class="mim-tip-reference" title="McKusick, V. A., Howell, R. R., Hussels, I. E., Neufeld, E. F., Stevenson, R. E. &lt;strong&gt;Allelism, nonallelism and genetic compounds among the mucopolysaccharidoses.&lt;/strong&gt; Lancet 299: 993-996, 1972. Note: Originally Volume I.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4112371/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4112371&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(72)91159-2&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4112371">McKusick et al. (1972)</a> suggested that the Hurler syndrome might be called MPS IH and the Scheie syndrome MPS IS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4112371" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The clinical features of Hurler syndrome include coarse facies, corneal clouding, mental retardation, hernias, dysostosis multiplex, and hepatosplenomegaly. Children with Hurler syndrome appear normal at birth and develop the characteristic appearance over the first years of life (<a href="#89" class="mim-tip-reference" title="Wraith, J. E., Rogers, J. G., Danks, D. M. &lt;strong&gt;The mucopolysaccharidoses.&lt;/strong&gt; Aust. Paediat. J. 23: 329-334, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3124802/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3124802&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1440-1754.1987.tb00284.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3124802">Wraith et al., 1987</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3124802" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#89" class="mim-tip-reference" title="Wraith, J. E., Rogers, J. G., Danks, D. M. &lt;strong&gt;The mucopolysaccharidoses.&lt;/strong&gt; Aust. Paediat. J. 23: 329-334, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3124802/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3124802&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1440-1754.1987.tb00284.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3124802">Wraith et al. (1987)</a> reviewed 27 Hurler patients, 10 of which were evaluated prior to biochemical diagnosis. Diagnosis was established at a mean age of 21 months (range, 5-63 months). Seventeen of the children (63%) came to clinical attention with hernia prior to the diagnosis of Hurler syndrome. The average age at death was 6.25 years in their series of 27 patients with a range of 1.3 to 10.9 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3124802" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Cleary, M. A., Wraith, J. E. &lt;strong&gt;The presenting features of mucopolysaccharidosis type IH (Hurler syndrome).&lt;/strong&gt; Acta Paediat. 84: 337-339, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7780260/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7780260&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1651-2227.1995.tb13640.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7780260">Cleary and Wraith (1995)</a> described the presenting features of 39 patients with mucopolysaccharidosis type IH. The mean age at diagnosis was approximately 9 months in this study. An earlier age at diagnosis is likely to lead to better results following therapy such as bone marrow transplantation. Clinical features that should arouse suspicion of MPS IH include frequent ear, nose and throat surgery and recurrent hernias. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7780260" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#47" class="mim-tip-reference" title="McDowell, G. A., Cowan, T. M., Blitzer, M. G., Greene, C. L. &lt;strong&gt;Intrafamilial variability in Hurler syndrome and Sanfilippo syndrome type A: implications for evaluation of new therapies.&lt;/strong&gt; Am. J. Med. Genet. 47: 1092-1095, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7507293/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7507293&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320470732&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7507293">McDowell et al. (1993)</a> described a family in which sibs with comparable deficiencies of alpha-L-iduronidase had rather different clinical severity and disease progression. The cases underscored the need for caution in counseling and the limitations of using sibs as controls in evaluating the outcome of treatment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7507293" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Head and Neck</em></strong></p><p>
<a href="#28" class="mim-tip-reference" title="Gorlin, R. J., Cohen, M. M., Jr., Hennekam, R. C. M. &lt;strong&gt;Syndromes of the Head and Neck. (4th ed.)&lt;/strong&gt; New York: Oxford Univ. Press (pub.) 2001."None>Gorlin et al. (2001)</a> described the facial phenotype. A slight coarsening of the facial features at 3 to 6 months of age is usually the first abnormality detected. The head is large with bulging frontal bones. The skull is often scaphocephalic secondary to premature closure of the metopic and sagittal sutures. The nasal bridge is depressed with broad nasal tip and anteverted nostrils. The cheeks are full. The lips are enlarged and the mouth is usually held open, particularly after age 3 years. Chronic nasal discharge is present.</p><p>Corneal clouding is common. Optic nerve head swelling was observed in 8 of 14 eyes of Hurler syndrome patients reported by <a href="#15" class="mim-tip-reference" title="Collins, M. L., Traboulsi, E. I., Maumenee, I. H. &lt;strong&gt;Optic nerve head swelling and optic atrophy in the systemic mucopolysaccharidoses.&lt;/strong&gt; Ophthalmology 97: 1445-1449, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2123975/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2123975&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0161-6420(90)32400-4&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2123975">Collins et al. (1990)</a>. Glaucoma has also been reported to occur in MPS IH (<a href="#56" class="mim-tip-reference" title="Nowaczyk, M. J., Clarke, J. T. R., Morin, J. D. &lt;strong&gt;Glaucoma as an early complication of Hurler&#x27;s disease.&lt;/strong&gt; Arch. Dis. Child. 63: 1091-1093, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3140740/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3140740&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/adc.63.9.1091&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3140740">Nowaczyk et al., 1988</a>). Retinal degeneration commonly occurs in MPS I (<a href="#11" class="mim-tip-reference" title="Caruso, R. C., Kaiser-Kupfer, M. I., Muenzer, J., Ludwig, I. H., Zasloff, M. A., Mercer, P. A. &lt;strong&gt;Electroretinographic findings in the mucopolysaccharidoses.&lt;/strong&gt; Ophthalmology 93: 1612-1616, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3101020/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3101020&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0161-6420(86)33537-1&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3101020">Caruso et al., 1986</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3101020+2123975+3140740" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#34" class="mim-tip-reference" title="Huang, C.-T., Chu, S.-Y., Lee, Y.-C. &lt;strong&gt;Optical coherence tomography of chorioretinopathy caused by mucopolysaccharidoses.&lt;/strong&gt; Ophthalmology 122: 1535-1537, 2015.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25864794/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;25864794&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ophtha.2015.01.015&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="25864794">Huang et al. (2015)</a> studied the chorioretinopathy in 3 patients with MPS I. The first patient (28 years old) exhibited multifocal depigmented retinopathy in both eyes. The second patient (12 years old) had mild parafoveal retinal folds and mild swollen discs in both eyes. The third patient (33 years old) had a myelinated nerve fiber layer in the right eye. In the first patient, spectral-domain optical coherence tomography (SD-OCT) showed focal choroidal thinning in the depigmented retinopathy areas. In the other 2 patients, SD-OCT showed a fuzzy and thickened external limiting membrane at the fovea. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25864794" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The neck is short and there is odontoid hypoplasia. Vertebral subluxation with cord compression can occur (<a href="#79" class="mim-tip-reference" title="Thomas, S. L., Childress, M. H., Quinton, B. &lt;strong&gt;Hypoplasia of the odontoid with atlantoaxial subluxation in Hurler&#x27;s syndrome.&lt;/strong&gt; Pediat. Radiol. 15: 353-354, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3929221/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3929221&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF02386776&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3929221">Thomas et al., 1985</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3929221" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a review of cervical spine x-rays in 21 children with mucopolysaccharidosis, <a href="#4" class="mim-tip-reference" title="Belani, K. G., Krivit, W., Carpenter, B. L. M., Braulin, E., Buckley, J. J., Liao, J.-C., Floyd, T., Leonard, A. S., Summers, C. G., Levine, S., Whitley, C. B. &lt;strong&gt;Children with mucopolysaccharidosis: perioperative care, morbidity, mortality, and new findings.&lt;/strong&gt; J. Pediat. Surg. 28: 403-410, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8468655/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8468655&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-3468(93)90240-l&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8468655">Belani et al. (1993)</a> found odontoid hypoplasia in 94%, with 38% demonstrating C1-C2 subluxation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8468655" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Cardiovascular Features</em></strong></p><p>
Cardiac disease is common. Acute cardiomyopathy associated with endocardial fibroelastosis has been a presenting condition in some infants with MPS I less than 1 year of age (<a href="#21" class="mim-tip-reference" title="Donaldson, M. D., Pennock, C. A., Berry, P. J., Duncan, A. W., Cawdery, J. E., Leonard, J. V. &lt;strong&gt;Hurler syndrome with cardiomyopathy in infancy.&lt;/strong&gt; J. Pediat. 114: 430-432, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2493520/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2493520&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(89)80565-7&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2493520">Donaldson et al., 1989</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2493520" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#41" class="mim-tip-reference" title="Krovetz, L. J., Lorincz, A. E., Schiebler, G. L. &lt;strong&gt;Cardiovascular manifestations of Hurler syndrome: hemodynamic and angiocardiographic observations in 15 patients.&lt;/strong&gt; Circulation 31: 132-141, 1965.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14247525/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14247525&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1161/01.cir.31.1.132&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14247525">Krovetz et al. (1965)</a> reviewed the cardiovascular findings in 58 autopsy reports. There was valvular involvement in 40 of 58 cases, coronary artery narrowing in 20 of 58 patients, and endocardial fibroelastosis in 11 of 58 patients. They suggested that coronary insufficiency can occur but that Hurler patients are prohibited by their retarded development to communicate this effectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14247525" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#63" class="mim-tip-reference" title="Renteria, V. G., Ferrans, V. J., Roberts, W. C. &lt;strong&gt;The heart in the Hurler syndrome: gross, histologic and ultrastructural observations in five necropsy cases.&lt;/strong&gt; Am. J. Cardiol. 38: 487-501, 1976.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/823811/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;823811&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0002-9149(76)90468-9&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="823811">Renteria et al. (1976)</a> described the cardiac disease in 5 necropsy cases of Hurler syndrome. All had narrowing of the extramural coronary arteries, cardiac valve thickening (left-sided greater than right-sided), generalized thickening of mural endocardium, and 'stiffening' of the myocardial walls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=823811" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#87" class="mim-tip-reference" title="Wippermann, C.-F., Beck, M., Schranz, D., Huth, R., Michel-Behnke, I., Jungst, B.-K. &lt;strong&gt;Mitral and aortic regurgitation in 84 patients with mucopolysaccharidoses.&lt;/strong&gt; Europ. J. Pediat. 154: 98-101, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7720756/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7720756&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF01991908&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7720756">Wippermann et al. (1995)</a> studied 84 patients with MPS disorders. Echocardiography revealed mitral regurgitation in 10 of 12 MPS IH patients and aortic regurgitation in 4 of 12 MPS IH patients. Aortic and mitral valve thickening was also detected in the patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7720756" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Braunlin, E., Miettunen, K., Lund, T., Luquette, M., Orchard, P. &lt;strong&gt;Hematopoietic cell transplantation for severe MPS I in the first six months of life: the heart of the matter.&lt;/strong&gt; Molec. Genet. Metab. 126: 117-120, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/30503158/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;30503158&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2018.11.007&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="30503158">Braunlin et al. (2019)</a> described cardiac features in 7 infants with MPS IH who had hematopoietic stem cell transplantation (HCT) before 6 months of age. Prior to HCT, 2 patients had mitral regurgitation, 3 had patent foramen ovale, and 1 patient had atrial flutter and severely decreased cardiac function requiring intensive care management. After HCT, 2 patients had mitral regurgitation, 2 had left ventricular hypertrophy, and 3 had patent foramen ovale. One patient died unexpectedly 69 days post-HCT. Overall survival was not increased compared to a cohort of patients who had HCT between 6 and 18 months of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30503158" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Respiratory Features</em></strong></p><p>
Frequent upper and lower respiratory tract infections are common. Respiratory obstruction occurs secondary to enlargement of tonsils and adenoids (<a href="#72" class="mim-tip-reference" title="Shapiro, J., Strome, M., Crocker, A. C. &lt;strong&gt;Airway obstruction and sleep apnea in Hurler and Hunter syndromes.&lt;/strong&gt; Ann. Otol. Rhinol. Laryng. 94: 458-461, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3931528/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3931528&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1177/000348948509400508&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3931528">Shapiro et al., 1985</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3931528" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Narrow tracheas also contribute to upper airway construction. <a href="#60" class="mim-tip-reference" title="Peters, M. E., Arya, S., Langer, L. O., Gilbert, E. F., Carlson, R., Adkins, W. &lt;strong&gt;Narrow trachea in mucopolysaccharidoses.&lt;/strong&gt; Pediat. Radiol. 15: 225-228, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3923421/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3923421&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF02388760&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3923421">Peters et al. (1985)</a> reported that 9 of 56 patients with MPS disorders had small tracheal diameters on their frontal chest radiographs. Autopsy of an MPS IH patient whose tracheal diameter measured 5 mm revealed that the epiglottis, aryepiglottic folds, and the vocal cords were enlarged and mainstem bronchi were thickened. This resulted primarily from glycosaminoglycan deposition in the connective tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3923421" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#71" class="mim-tip-reference" title="Semenza, G. L., Pyeritz, R. E. &lt;strong&gt;Respiratory complications of mucopolysaccharide storage disorders.&lt;/strong&gt; Medicine 67: 209-219, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3134589/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3134589&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/00005792-198807000-00002&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3134589">Semenza and Pyeritz (1988)</a> studied respiratory complications in 4 patients with MPS IH. All had tonsillar and adenoidal hypertrophy, tongue enlargement, and supraglottic narrowing. Two patients studied by polysomnography had obstructive sleep apnea. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3134589" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Belani, K. G., Krivit, W., Carpenter, B. L. M., Braulin, E., Buckley, J. J., Liao, J.-C., Floyd, T., Leonard, A. S., Summers, C. G., Levine, S., Whitley, C. B. &lt;strong&gt;Children with mucopolysaccharidosis: perioperative care, morbidity, mortality, and new findings.&lt;/strong&gt; J. Pediat. Surg. 28: 403-410, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8468655/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8468655&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-3468(93)90240-l&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8468655">Belani et al. (1993)</a> described the perioperative care in 30 children with MPS disorders, including 21 Hurler or Hurler-Scheie patients. They described anesthetic results in 14 patients with Hunter syndrome. During laryngoscopy, vocal cords were visible in only 19 of 55 anesthetic events. Following extubation, upper airway obstruction was noted 25 times. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8468655" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Musculoskeletal System</em></strong></p><p>
Length is often normal until about 2 years of age when growth stops; by age 3 years height is less than the third percentile (<a href="#28" class="mim-tip-reference" title="Gorlin, R. J., Cohen, M. M., Jr., Hennekam, R. C. M. &lt;strong&gt;Syndromes of the Head and Neck. (4th ed.)&lt;/strong&gt; New York: Oxford Univ. Press (pub.) 2001."None>Gorlin et al., 2001</a>).</p><p>In infancy, bone trabeculation is coarse. In late infancy and childhood, a pattern of skeletal changes called 'dysostosis multiplex' develops (<a href="#50" class="mim-tip-reference" title="McKusick, V. A. &lt;strong&gt;Heritable Disorders of Connective Tissue. (4th ed.)&lt;/strong&gt; St. Louis: C. V. Mosby Co. (pub.) 1972."None>McKusick, 1972</a>). The skull is large with narrow orbits. The calvaria is thickened and the sagittal and lambdoidal sutures close prematurely. The sella becomes J-shaped. The ribs have been described as oar-shaped with narrowing at the vertebral ends and broadening at the sternal ends. Clavicles are short, thick, and irregular. The vertebral bodies are dysplastic with biconcave endplates and hook-shaped configuration of the lower thoracic and upper lumbar vertebral bodies. The pelvis is poorly formed with small femoral heads and coxa valga. Iliac wings are flared. The long tubular bones show diaphyseal widening with small, deformed epiphyses. Phalanges are bullet-shaped with proximal pointing of the second to fifth metacarpals.</p><p><a href="#54" class="mim-tip-reference" title="Neuhauser, E. B. D., Griscom, N. T., Gilles, F. H. &lt;strong&gt;Arachnoid cysts in the Hurler-Hunter syndrome.&lt;/strong&gt; Ann. Radiol. 11: 453-469, 1968.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5006799/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5006799&lt;/a&gt;]" pmid="5006799">Neuhauser et al. (1968)</a> concluded that subarachnoid cysts are often responsible for the enlarged sella in Hurler syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5006799" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Joint stiffness is a common feature of all the MPS disorders with the exception of Morquio syndrome (<a href="/entry/253000">253000</a>; <a href="/entry/253010">253010</a>). The joint function abnormalities probably result from a combination of the metaphyseal deformities and thickened joint capsules secondary to glycosaminoglycan deposition and fibrosis (<a href="#53" class="mim-tip-reference" title="Neufeld, E. F., Muenzer, J. &lt;strong&gt;The mucopolysaccharidoses. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic &amp; Molecular Bases of Inherited Disease. Vol. III. (8th ed.)&lt;/strong&gt; New York: McGraw-Hill (pub.) 2001."None>Neufeld and Muenzer, 2001</a>).</p><p>Progressive lumbar gibbus or kyphosis is commonly seen in the MPS disorders (<a href="#53" class="mim-tip-reference" title="Neufeld, E. F., Muenzer, J. &lt;strong&gt;The mucopolysaccharidoses. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic &amp; Molecular Bases of Inherited Disease. Vol. III. (8th ed.)&lt;/strong&gt; New York: McGraw-Hill (pub.) 2001."None>Neufeld and Muenzer, 2001</a>). <a href="#77" class="mim-tip-reference" title="Tandon, V., Williamson, J. B., Cowie, R. A., Wraith, J. E. &lt;strong&gt;Spinal problems in mucopolysaccharidosis I (Hurler syndrome).&lt;/strong&gt; J. Bone Joint Surg. Br. 78: 938-944, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8951011/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8951011&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1302/0301-620x78b6.1279&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8951011">Tandon et al. (1996)</a> described the spinal problems and their management in 12 patients with Hurler syndrome who were followed up for a mean of 4.5 years following bone marrow transplantation. High lumbar kyphosis was seen in 10 patients and was associated with thoracic scoliosis in 1. Isolated thoracic scoliosis was seen in another. One patient had no significant problems in the thoracic or lumbar spine but had odontoid hypoplasia, which was also seen in 3 other children. Four of the 8 patients in whom MRI of the cervical spine had been performed had abnormal soft tissue around the tip of the odontoid. Neurologic problems were seen in 2 patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8951011" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Carpal tunnel syndrome, a common complication in the mucopolysaccharidoses, probably results from a combination of excessive lysosomal storage in the connective tissue of the flexor retinaculum and a deformity secondary to the underlying skeletal dysplasia. <a href="#88" class="mim-tip-reference" title="Wraith, J. E., Alani, S. M. &lt;strong&gt;Carpal tunnel syndrome in the mucopolysaccharidoses and related disorders.&lt;/strong&gt; Arch. Dis. Child. 65: 962-963, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2121106/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2121106&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/adc.65.9.962&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2121106">Wraith and Alani (1990)</a> performed nerve conduction studies on 18 patients with various forms of mucopolysaccharidoses and mucolipidosis III. All patients studied, with the exception of patients younger than 2 years, had evidence of thenar muscle wasting and a typical 'claw-hand' deformity. All 3 patients with MPS IH were found to have carpal tunnel syndrome. Two of the 3 received bone marrow transplantation at 14 months and 2.3 years, respectively. Neither showed improvement following transplantation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2121106" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Nervous System</em></strong></p><p>
Developmental delay is often apparent by 12 to 24 months of age, with a maximum functional age of 2 to 4 years followed by progressive deterioration. Most children develop limited language because of developmental delay, chronic hearing loss, and enlarged tongue (<a href="#53" class="mim-tip-reference" title="Neufeld, E. F., Muenzer, J. &lt;strong&gt;The mucopolysaccharidoses. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic &amp; Molecular Bases of Inherited Disease. Vol. III. (8th ed.)&lt;/strong&gt; New York: McGraw-Hill (pub.) 2001."None>Neufeld and Muenzer, 2001</a>).</p><p>In a study of 27 patients with MPS IH, <a href="#89" class="mim-tip-reference" title="Wraith, J. E., Rogers, J. G., Danks, D. M. &lt;strong&gt;The mucopolysaccharidoses.&lt;/strong&gt; Aust. Paediat. J. 23: 329-334, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3124802/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3124802&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1440-1754.1987.tb00284.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3124802">Wraith et al. (1987)</a> found that all had head circumferences at or above the 95th percentile. Only 5 children developed signs and symptoms of raised intracranial pressure which required shunt. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3124802" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#42" class="mim-tip-reference" title="Lee, C., Dineen, T. E., Brack, M., Kirsch, J. E., Runge, V. M. &lt;strong&gt;The mucopolysaccharidoses: characterization by cranial MR imaging.&lt;/strong&gt; Am. J. Neuroradiol. 14: 1285-1292, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8279321/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8279321&lt;/a&gt;]" pmid="8279321">Lee et al. (1993)</a> characterized cranial MRI findings in 6 children with Hurler syndrome. All exhibited cribriform or cystic changes: low signal intensity with respect to white matter on T1-weighted images and high-signal intensity on the T2-weighted images. The changes corresponded pathologically to perivascular accumulations of glycosaminoglycan within the foam cells in the Virchow-Robin spaces (<a href="#55" class="mim-tip-reference" title="Norman, R. M., Urich, H., France, N. E. &lt;strong&gt;Perivascular cavitation of the basal ganglia in gargoylism.&lt;/strong&gt; J. Ment. Sci. 105: 1070-1077, 1959.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14427626/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14427626&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1192/bjp.105.441.1070&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14427626">Norman et al., 1959</a>). Myelination delay, atrophy, and ventricular enlargement were also found in their patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=14427626+8279321" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Dermatologic Features</em></strong></p><p>
<a href="#31" class="mim-tip-reference" title="Hanson, M., Lupski, J. R., Hicks, J., Metry, D. &lt;strong&gt;Association of dermal melanocytosis with lysosomal storage disease: clinical features and hypotheses regarding pathogenesis.&lt;/strong&gt; Arch. Derm. 139: 916-920, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12873889/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12873889&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archderm.139.7.916&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12873889">Hanson et al. (2003)</a> described 2 infants with extensive dermal melanocytosis in association with GM1-gangliosidosis type I (<a href="/entry/230500">230500</a>) and Hurler syndrome, respectively. Clinically, dermal melanocytosis associated with lysosomal storage disease is characterized by extensive, blue cutaneous pigmentation with dorsal and ventral distribution, indistinct borders, and persistent and/or 'progressive' behavior. A literature analysis revealed 37 additional cases. The most common lysosomal storage disease associated with dermal melanocytosis was Hurler syndrome (24 of 39 cases), followed by GM1-gangliosidosis (11 of 39 cases). <a href="#31" class="mim-tip-reference" title="Hanson, M., Lupski, J. R., Hicks, J., Metry, D. &lt;strong&gt;Association of dermal melanocytosis with lysosomal storage disease: clinical features and hypotheses regarding pathogenesis.&lt;/strong&gt; Arch. Derm. 139: 916-920, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12873889/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12873889&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archderm.139.7.916&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12873889">Hanson et al. (2003)</a> concluded that in the appropriate clinical setting, an unusual presentation of dermal melanocytosis in an infant may be a cutaneous sign of an underlying lysosomal storage disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12873889" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="biochemicalFeatures" class="mim-anchor"></a>
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<p>The enzyme deficient in Hurler syndrome is alpha-L-iduronidase (<a href="/entry/252800">252800</a>).</p><p><a href="#16" class="mim-tip-reference" title="Danes, B. S., Bearn, A. G. &lt;strong&gt;Hurler&#x27;s syndrome: demonstration of an inherited disorder of connective tissue in cell culture.&lt;/strong&gt; Science 149: 987-989, 1965.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4953285/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4953285&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1126/science.149.3687.987&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4953285">Danes and Bearn (1965)</a> found that cellular accumulation of mucopolysaccharides persists in cultured fibroblasts. <a href="#23" class="mim-tip-reference" title="Fratantoni, J. C., Hall, C. W., Neufeld, E. F. &lt;strong&gt;Hurler and Hunter syndromes: mutual correction of the defect in cultured fibroblasts.&lt;/strong&gt; Science 162: 570-572, 1968.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4236721/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4236721&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1126/science.162.3853.570&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4236721">Fratantoni et al. (1968)</a> showed that the accumulation results from inefficient degradation of intracellular mucopolysaccharide rather than excessive synthesis or reduced secretion. Furthermore, they found that mixing of fibroblasts from Hurler and Hunter patients causes mutual correction of the intracellular accumulation of mucopolysaccharides. Medium in which cells of the other type or normal cells had been incubated was also effective in correcting the defect. Thus, isolation and identification of the corrective factor in the medium opened up possibilities of clarifying the normal mechanisms of MPS degradation, as well as therapy. Differentiation of the Sanfilippo syndrome (MPS III; see <a href="/entry/252900">252900</a>) from the Hurler and Hunter syndromes was also possible by this mixed culture method. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4236721+4953285" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#86" class="mim-tip-reference" title="Wiesmann, U. N., Neufeld, E. F. &lt;strong&gt;Scheie and Hurler syndromes: apparent identity of the biochemical defect.&lt;/strong&gt; Science 169: 72-74, 1970.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4246082/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4246082&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1126/science.169.3940.72&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4246082">Wiesmann and Neufeld (1970)</a> found no cross-correction of Scheie and Hurler fibroblasts with those from Sanfilippo and Hunter patients. Both disorders showed deficiencies of alpha-L-iduronidase. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4246082" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#65" class="mim-tip-reference" title="Schuchman, E. H., Desnick, R. J. &lt;strong&gt;Mucopolysaccharidosis type I subtypes: presence of immunologically cross-reactive material and in vitro enhancement of the residual alpha-L-iduronidase activities.&lt;/strong&gt; J. Clin. Invest. 81: 98-105, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3121676/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3121676&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI113317&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3121676">Schuchman and Desnick (1988)</a> reported the presence of cross-reactive immunologic material (CRIM) in individuals from each of the 3 MPS I subtypes. Furthermore, they identified effector compounds that enhanced the residual activities in subtype extracts into the heterozygote range. The polyclonal antibody with which this work was done, however, is under suspicion because of the findings of <a href="#67" class="mim-tip-reference" title="Scott, H. S., Ashton, L. J., Eyre, H. J., Baker, E., Brooks, D. A., Callen, D. F., Sutherland, G. R., Morris, C. P., Hopwood, J. J. &lt;strong&gt;Chromosomal localization of the human alpha-L-iduronidase gene (IDUA) to 4p16.3.&lt;/strong&gt; Am. J. Hum. Genet. 47: 802-807, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2220820/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2220820&lt;/a&gt;]" pmid="2220820">Scott et al. (1990)</a> that it gave a fallacious result when used for the mapping of the IDUA gene in somatic cell hybrids. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3121676+2220820" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Brooks, D. A., Harper, G. S., Gibson, G. L., Ashton, L. J., Taylor, J. A., McCourt, P. A. G., Freeman, C., Clements, P. R., Hoffman, J. W., Hopwood, J. J. &lt;strong&gt;Hurler syndrome: a patient with abnormally high levels of alpha-L-iduronidase protein.&lt;/strong&gt; Biochem. Med. Metab. Biol. 47: 211-220, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1627351/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1627351&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0885-4505(92)90028-w&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1627351">Brooks et al. (1992)</a> found that a clinically typical patient with Hurler syndrome, the source of cell line GM2827, had, despite severe deficiency of enzyme, an activity level of alpha-L-iduronidase protein at least 6 times greater than the mean level found in normal control fibroblasts. This was the only 1 of 23 patients who had protein levels greater than 7% of the mean level detected in normal controls. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1627351" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="diagnosis" class="mim-anchor"></a>
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<p><strong><em>Biochemical Diagnosis</em></strong></p><p>
The earliest diagnostic tests for the MPS disorders were based on the urinary excretion of glycosaminoglycans. <a href="#58" class="mim-tip-reference" title="Pennock, C. A. &lt;strong&gt;A review and selection of simple laboratory methods used for the study of glycosaminoglycan excretion and the diagnosis of the mucopolysaccharidoses.&lt;/strong&gt; J. Clin. Path. 29: 111-123, 1976.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/132459/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;132459&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jcp.29.2.111&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="132459">Pennock (1976)</a> noted several methods that had been developed from semiquantitative spot tests to more precise qualitative and quantitative assays. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=132459" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Spot tests are quick and inexpensive but are subject to both false-positive and false-negative results. <a href="#17" class="mim-tip-reference" title="de Jong, J. G. N., Hasselman, J. J. F., van Landeghem, A. A. J., Vader, H. L., Wevers, R. A. &lt;strong&gt;The spot test is not a reliable screening procedure for mucopolysaccharidoses.&lt;/strong&gt; Clin. Chem. 37: 572-575, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1901775/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1901775&lt;/a&gt;]" pmid="1901775">De Jong et al. (1991)</a> checked the reliability of the Ames MPS paper spot test, which is based on the Azure A dye. They sent a series of urine samples to 3 laboratories where the spot test is part of the metabolic screening for mucopolysaccharidoses. In these laboratories, false-negative results ranged between 19% and 35% and false-positive results ranged between 12 and 29% of all samples submitted. In contrast, the quantitative dimethylmethylene blue test detected an increased glycosaminoglycan content in all urine samples from mucopolysaccharidosis patients and gave no false-positive results. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1901775" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Definitive diagnosis is established by alpha-L-iduronidase enzyme assay using artificial substrates (fluorogenic or chromogenic) in cultured fibroblasts or isolated leukocytes (<a href="#30" class="mim-tip-reference" title="Hall, C. W., Liebaers, I., Di Natale, P., Neufeld, E. F. &lt;strong&gt;Enzymic diagnosis of the genetic mucopolysaccharide storage disorders.&lt;/strong&gt; Methods Enzymol. 50: 439-456, 1978.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/26836/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;26836&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0076-6879(78)50048-7&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="26836">Hall et al., 1978</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26836" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Carrier testing can be performed by differentiating normal enzyme activity from half-normal levels of enzyme activity. <a href="#83" class="mim-tip-reference" title="Wappner, R. S., Brandt, I. K. &lt;strong&gt;Hurler syndrome: alpha-L-iduronidase activity in leukocytes as a method for heterozygote detection.&lt;/strong&gt; Pediat. Res. 10: 629-632, 1976.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/818611/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;818611&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/00006450-197606000-00013&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="818611">Wappner and Brandt (1976)</a> studied alpha-L-iduronidase activity in mixed leukocyte preparations in 10 families in which the Hurler syndrome had occurred. Affected patients, heterozygotes, and normal subjects were clearly distinguished by alpha-L-iduronidase activity alone. Patients had 0 to 3%, obligate heterozygotes 19 to 60%, and normal subjects 83 to 121% of the mean normal activity. There was no overlap between heterozygotes and normal subjects. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=818611" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Low activity 'pseudodeficiency' alleles exist, however, and complicate biochemical carrier testing. <a href="#78" class="mim-tip-reference" title="Taylor, H. A., Thomas, G. H. &lt;strong&gt;Pseudodeficiency of alpha-iduronidase.&lt;/strong&gt; J. Inherit. Metab. Dis. 16: 1058-1059, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8127064/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8127064&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00711533&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8127064">Taylor and Thomas (1993)</a> reported apparent deficiency of alpha-iduronidase in a clinically normal individual. The same finding was made in leukocytes and skin fibroblasts which functioned normally in correction assays in mixed culture. Previously reported instances of pseudodeficiency involved individuals who were obligate heterozygotes for Hurler syndrome, having 1 Hurler allele and presumably 1 pseudodeficiency allele (<a href="#24" class="mim-tip-reference" title="Gatti, R., Borrone, C., Filocamo, M., Pannone, N., DiNatale, P. &lt;strong&gt;Prenatal diagnosis of mucopolysaccharidosis I: a special difficulty arising from an unusually low enzyme activity in mother&#x27;s cells.&lt;/strong&gt; Prenatal Diag. 5: 149-154, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3921950/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3921950&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/pd.1970050209&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3921950">Gatti et al., 1985</a>; <a href="#84" class="mim-tip-reference" title="Whitley, C. B., Gorlin, R. J., Krivit, W. &lt;strong&gt;A nonpathologic allele (IW) for low alpha-L-iduronidase enzyme activity vis-a-vis prenatal diagnosis of Hurler syndrome.&lt;/strong&gt; Am. J. Med. Genet. 28: 233-243, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3118714/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3118714&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320280136&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3118714">Whitley et al., 1987</a>). <a href="#84" class="mim-tip-reference" title="Whitley, C. B., Gorlin, R. J., Krivit, W. &lt;strong&gt;A nonpathologic allele (IW) for low alpha-L-iduronidase enzyme activity vis-a-vis prenatal diagnosis of Hurler syndrome.&lt;/strong&gt; Am. J. Med. Genet. 28: 233-243, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3118714/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3118714&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320280136&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3118714">Whitley et al. (1987)</a> described a low activity 'pseudodeficiency' allele at the alpha-L-iduronidase locus. It was found in a phenotypically normal obligate heterozygote with exceedingly low levels of enzyme activity. The presence of this allele can complicate carrier detection and prenatal diagnosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3921950+3118714+8127064" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Prenatal Diagnosis</em></strong></p><p>
Prenatal diagnosis is possible on both cultured amniotic fluid cells and chorionic villus biopsies. <a href="#91" class="mim-tip-reference" title="Young, E. P. &lt;strong&gt;Prenatal diagnosis of Hurler disease by analysis of alpha-iduronidase in chorionic villi.&lt;/strong&gt; J. Inherit. Metab. Dis. 15: 224-230, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1527990/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1527990&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF01799636&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1527990">Young (1992)</a> stressed the importance of obtaining an adequate chorionic villi tissue sample. Twenty-four pregnancies at risk for Hurler disease were monitored by measurement of alpha-iduronidase in chorionic villi. Adequate samples were obtained for direct assay of the villi in 22 pregnancies. Pregnancies were terminated in 5 samples found to be affected. In another pregnancy, an equivocal result was obtained on direct assay, but analysis of the cultured chorionic cells showed the fetus to be affected. In 1 pregnancy in which a very small sample was obtained, direct assay indicated the fetus to be unaffected. However, amniocentesis revealed an affected pregnancy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1527990" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Molecular Diagnosis</em></strong></p><p>
Molecular diagnosis of Hurler syndrome is difficult because of the genetic heterogeneity in MPS I. Using a combination of mutation analysis and mutation scanning in a study of 85 MPS I families (73 Hurler, 5 Hurler/Scheie, 7 Scheie), <a href="#3" class="mim-tip-reference" title="Beesley, C. E., Meaney, C. A., Greenland, G., Adams, V., Vellodi, A., Young, E. P., Winchester, B. G. &lt;strong&gt;Mutational analysis of 85 mucopolysaccharidosis type I families: frequency of known mutations, identification of 17 novel mutations and in vitro expression of missense mutations.&lt;/strong&gt; Hum. Genet. 109: 503-511, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11735025/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11735025&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s004390100606&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11735025">Beesley et al. (2001)</a> identified both IDUA mutations in 81 (95%) families, one IDUA mutation in 3 (3.5%) families, and none in 1 (1.1%) family. The families were screened for 9 known mutations. W402X (<a href="/entry/252800#0001">252800.0001</a>) was the most frequent mutation in their population (45.3%), followed by Q70X (<a href="/entry/252800#0002">252800.0002</a>) (15.9%). In 30 families, one or both of the mutations were not identified, which accounted for 25.9% of the total alleles. Therefore, all 14 exons of the IDUA gene were screened in these patients and 23 different sequence changes were found, 17 of which were previously unknown. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11735025" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#81" class="mim-tip-reference" title="Wang, R. Y., Bodamer, O. A., Watson, M. S., Wilcox, W. R. &lt;strong&gt;Lysosomal storage diseases: diagnostic confirmation and management of presymptomatic individuals.&lt;/strong&gt; Genet. Med. 13: 457-484, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21502868/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;21502868&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/GIM.0b013e318211a7e1&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="21502868">Wang et al. (2011)</a> described the ACMG standards and guidelines for the diagnostic confirmation and management of presymptomatic individuals with lysosomal storage diseases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21502868" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Anesthesia</em></strong></p><p>
<a href="#4" class="mim-tip-reference" title="Belani, K. G., Krivit, W., Carpenter, B. L. M., Braulin, E., Buckley, J. J., Liao, J.-C., Floyd, T., Leonard, A. S., Summers, C. G., Levine, S., Whitley, C. B. &lt;strong&gt;Children with mucopolysaccharidosis: perioperative care, morbidity, mortality, and new findings.&lt;/strong&gt; J. Pediat. Surg. 28: 403-410, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8468655/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8468655&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-3468(93)90240-l&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8468655">Belani et al. (1993)</a> described the perioperative care, morbidity, and mortality in 30 patients with mucopolysaccharidosis, including 21 patients with Hurler or Hurler-Scheie syndrome. During 141 anesthetic administrations, 2 children with Hurler syndrome died intraoperatively. The first death occurred in a boy, aged 3 years 9 months, who demonstrated a sudden elevation of ST-T segments on ECG, then rapid bradycardia and death. At autopsy, both his coronary vessels were occluded. The other death occurred in a 14-month-old child who had normal preoperative ECG and cardiac echocardiogram. During cardiac catheterization, he developed ventricular tachycardia and subsequent cardiac arrest. At autopsy, there was marked concentric intimal and subintimal fibrosis of both coronary arteries, which was not substantiated on the coronary angiogram. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8468655" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Plasma Infusion/Fibroblast Transplantation</em></strong></p><p>
Improvement, clinical and chemical, with plasma infusions was claimed by <a href="#19" class="mim-tip-reference" title="Di Ferrante, N. M., Nichols, B. L., Jr., Donnelly, P. V., Neri, G., Hrgovcic, R., Berglund, R. K. &lt;strong&gt;Induced degradation of glycosaminoglycans in Hurler&#x27;s and Hunter&#x27;s syndromes by plasma infusion.&lt;/strong&gt; Proc. Nat. Acad. Sci. 68: 303-307, 1971.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5277074/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5277074&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.68.2.303&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="5277074">Di Ferrante et al. (1971)</a>, but further trials were disappointing. <a href="#27" class="mim-tip-reference" title="Gibbs, D. A., Spellacy, E., Tompkins, R., Watts, R. W. E., Mowbray, J. F. &lt;strong&gt;A clinical trial of fibroblast transplantation for the treatment of mucopolysaccharidoses.&lt;/strong&gt; J. Inherit. Metab. Dis. 6: 62-81, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6410119/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6410119&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF02338973&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6410119">Gibbs et al. (1983)</a> did not find fibroblast transplantation to be therapeutically useful in either Hurler syndrome or Sanfilippo syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5277074+6410119" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Bone Marrow Transplantation (BMT)</em></strong></p><p>
<a href="#35" class="mim-tip-reference" title="Hugh-Jones, K. &lt;strong&gt;Early diagnosis of mucopolysaccharidosis. (Letter)&lt;/strong&gt; Lancet 322: 1300 only, 1983. Note: Originally Volume II.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6139633/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6139633&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(83)91168-6&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6139633">Hugh-Jones (1983)</a> pointed out the importance of early diagnosis of mucopolysaccharidoses because of the effectiveness of bone marrow transplantation. He reported that hernia was a feature in 13 of 15 cases of MPS I and in 7 of 9 cases of MPS II, and suggested that hernia before the age of 6 months may be a valuable diagnostic clue. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6139633" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#33" class="mim-tip-reference" title="Hopwood, J. J., Vellodi, A., Scott, H. S., Morris, C. P., Litjens, T., Clements, P. R., Brooks, D. A., Cooper, A., Wraith, J. E. &lt;strong&gt;Long-term clinical progress in bone marrow transplanted mucopolysaccharidosis type I patients with a defined genotype.&lt;/strong&gt; J. Inherit. Metab. Dis. 16: 1024-1033, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8127052/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8127052&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00711520&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8127052">Hopwood et al. (1993)</a> described the outcome of bone marrow transplantation in 2 patients who were subsequently found to be homozygous for the relatively common W402X mutation (<a href="/entry/252800#0001">252800.0001</a>). They received BMT at the ages of 14 and 11 months and were 12% and 14 years old, respectively, at the time of report. Untreated patients homozygous for this mutation have a very severe clinical phenotype with rapid clinical deterioration and death before 6 years of age. The 12-year-old patient showed limited mobility but was coping well at school; the other patient was wheelchair-bound with severe disability in his lower limbs and attended a school for the physically handicapped. Both patients had less than normal intelligence with slowly continuing losses. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8127052" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The Storage Disease Collaborative Study Group (<a href="#59" class="mim-tip-reference" title="Peters, C., Shapiro, E. G., Anderson, J., Henslee-Downey, J., Klemperer, M. R., Cowan, M. J., Saunders, E. F., deAlarcon, P. A., Twist, C., Nachman, J. B., Hale, G. A., Harris, R. E., Rozans, M. K., Kurtzberg, J., Grayson, G. H., Williams, T. E., Lenarsky, C., Wagner, J. E., Krivit, W. &lt;strong&gt;Hurler syndrome. II. Outcome of HLA-genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children.&lt;/strong&gt; Blood 91: 2601-2608, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9516162/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9516162&lt;/a&gt;]" pmid="9516162">Peters et al., 1998</a>) reported their findings on 54 patients with MPS I. The patients received high-dose chemotherapy with or without irradiation and BMT from HLA-genotypically identical sib (GIS) or HLA-haploidentical-related (HIR) donors between 1983 and 1995. Thirty-nine of 54 patients (72%) were engrafted following the first BMT. The probability of grade II to IV acute graft-vs-host disease (GVHD; see <a href="/entry/614395">614395</a>) at 100 days was 32% for GIS and 55% for HIR patients. The actuarial probability of survival at 5 years was 64% for all patients, 75% for GIS patients, 53% for HIR patients, and 53% for patients with donor marrow engraftment. The baseline Mental Developmental Index (MDI) was examined both for children less than and greater than 24 months of age at BMT. Children who received a transplant before 24 months had a mean baseline MDI of 78, whereas those who received a transplant after 24 months of age had a mean baseline MDI of 63 (P = 0.0002). Both baseline and post-BMT neuropsychologic data were available for 26 of 30 engrafted survivors. Of 14 patients who received a transplant before 24 months of age, 9 demonstrated developmental trajectories that were normal or somewhat slower than normal. In contrast, of 12 patients who received a transplant after 24 months of age, only 3 showed developmental trajectories that were normal or somewhat slower than normal (P = 0.01). Children were more likely to maintain normal cognitive development if they were fully engrafted following BMT from a donor with homozygous normal leukocyte alpha-L-iduronidase enzyme activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9516162" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Enzyme Replacement</em></strong></p><p>
<a href="#36" class="mim-tip-reference" title="Kakkis, E. D., Muenzer, J., Tiller, G. E., Waber, L., Belmont, J., Passage, M., Izykowski, B., Phillips, J., Doroshow, R., Walot, I., Hoft, R., Neufeld, E. F. &lt;strong&gt;Enzyme-replacement therapy in mucopolysaccharidosis I.&lt;/strong&gt; New Eng. J. Med. 344: 182-188, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11172140/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11172140&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM200101183440304&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11172140">Kakkis et al. (2001)</a> treated 10 patients with MPS I (aged 5 to 22 years) with recombinant human alpha-L-iduronidase at a dose of 125,000 U per kg of body weight given intravenously once weekly for 52 weeks. Hepatosplenomegaly decreased significantly in all patients, and the size of the liver was normal for body weight and age in 8 patients by 26 weeks. The rate of growth in height and weight increased by a mean of 85%% and 131%, respectively, at 52 weeks in the 6 prepubertal patients. The mean maximum range of motion of shoulder flexion and elbow extension increased significantly. The number of episodes of apnea and hypopnea during sleep decreased by 61%. New York Heart Association functional class improved by 1 or 2 classes in all patients. Urinary glycosaminoglycan excretion decreased after 3 to 4 weeks of treatment; the mean reduction at 52 weeks was 63% of baseline values. Five patients had transient urticaria during infusions. Serum antibodies to alpha-L-iduronidase were detected in 4 patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11172140" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#82" class="mim-tip-reference" title="Wang, R. Y., Cambray-Forker, E. J., Ohanian, K., Karlin, D. S., Covault, K. K., Schwartz, P. H., Abdenur, J. E. &lt;strong&gt;Treatment reduces or stabilizes brain imaging abnormalities in patients with MPS I and II.&lt;/strong&gt; Molec. Genet. Metab. 98: 406-411, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19748810/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19748810&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2009.07.015&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19748810">Wang et al. (2009)</a> reported a girl with severe MPS I who began enzyme replacement therapy (ERT) at age 15 months and underwent hematopoietic stem cell transplantation at age 20 months. At that time, she had begun to walk and spoke a few words. She had complete engraftment with normalization of plasma IDUA activity. At age 4 years, she was slightly developmentally delayed with mild to moderate sensorineural hearing loss, but was making progress. Brain imaging studies showed improvement of white matter abnormalities and ventricular dilatation following ERT even before stem cell transplant, with continued improvement in brain imaging abnormalities until the time of the report. The findings suggested that ERT may improve brain MRI abnormalities in patients with MPS, even though ERT had previously been thought not to cross into the brain. <a href="#82" class="mim-tip-reference" title="Wang, R. Y., Cambray-Forker, E. J., Ohanian, K., Karlin, D. S., Covault, K. K., Schwartz, P. H., Abdenur, J. E. &lt;strong&gt;Treatment reduces or stabilizes brain imaging abnormalities in patients with MPS I and II.&lt;/strong&gt; Molec. Genet. Metab. 98: 406-411, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19748810/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19748810&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2009.07.015&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19748810">Wang et al. (2009)</a> offered some explanations, including lessening of somatic GAG accumulation, repair of damaged brain endothelium, and possibly small amounts of enzyme being able to permeate the brain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19748810" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Gene Therapy</em></strong></p><p>
Because allogeneic bone marrow transplantation is not available to all patients, <a href="#22" class="mim-tip-reference" title="Fairbairn, L. J., Lashford, L. S., Spooncer, E., McDermott, R. H., Lebens, G., Arrand, J. E., Arrand, J. R., Bellantuono, I., Holt, R., Hatton, C. E., Cooper, A., Besley, G. T. N., Wraith, J. E., Anson, D. S., Hopwood, J. J., Dexter, T. M. &lt;strong&gt;Long-term in vitro correction of alpha-L-iduronidase deficiency (Hurler syndrome) in human bone marrow.&lt;/strong&gt; Proc. Nat. Acad. Sci. 93: 2025-2030, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8700879/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8700879&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.93.5.2025&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8700879">Fairbairn et al. (1996)</a> considered an alternative approach based on transfer and expression of the normal gene in autologous bone marrow. They constructed a retroviral vector carrying the full-length cDNA for alpha-L-iduronidase and used it to transduce bone marrow from patients with this disorder. They demonstrated successful gene transfer into primitive CD34+ cells and subsequent enzyme expression in their maturing progeny. The efficiency of gene transfer as assessed by PCR analysis of hematopoietic colonies was 25 to 56%. The enzyme was secreted into the medium and functional localization was demonstrated by reversal of the phenotypic effects of lysosomal storage in macrophages. <a href="#22" class="mim-tip-reference" title="Fairbairn, L. J., Lashford, L. S., Spooncer, E., McDermott, R. H., Lebens, G., Arrand, J. E., Arrand, J. R., Bellantuono, I., Holt, R., Hatton, C. E., Cooper, A., Besley, G. T. N., Wraith, J. E., Anson, D. S., Hopwood, J. J., Dexter, T. M. &lt;strong&gt;Long-term in vitro correction of alpha-L-iduronidase deficiency (Hurler syndrome) in human bone marrow.&lt;/strong&gt; Proc. Nat. Acad. Sci. 93: 2025-2030, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8700879/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8700879&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.93.5.2025&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8700879">Fairbairn et al. (1996)</a> concluded that retroviral gene transfer into human bone marrow may offer effective gene therapy of Hurler syndrome in young patients without a matched sib donor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8700879" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#38" class="mim-tip-reference" title="Keeling, K. M., Brooks, D. A., Hopwood, J. J., Li, P., Thompson, J. N., Bedwell, D. M. &lt;strong&gt;Gentamicin-mediated suppression of Hurler syndrome stop mutations restores a low level of alpha-L-iduronidase activity and reduces lysosomal glycosaminoglycan accumulation.&lt;/strong&gt; Hum. Molec. Genet. 10: 291-299, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11159948/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11159948&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/10.3.291&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11159948">Keeling et al. (2001)</a> found that a Hurler syndrome fibroblast cell line heterozygous for the IDUA stop mutations Q70X and W402X showed a significant increase in alpha-L-iduronidase activity when cultured in the presence of gentamicin, resulting in the restoration of 2.8% of normal alpha-L-iduronidase activity. Gentamicin treatment reduced glycosaminoglycan accumulation in Hurler cells to a normal level for at least 2 days after gentamicin treatment was discontinued. The reduction in the GAG level was also reflected in a marked reduction in lysosomal vacuolation, as shown by fluorescence microscopy. The authors suggested that partial suppression of premature stop mutations by gentamicin may provide an effective treatment for Hurler syndrome patients with these mutations in the IDUA gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11159948" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="Di Natale, P., Di Domenico, C., Villani, G. R. D., Lombardo, A., Follenzi, A., Naldini, L. &lt;strong&gt;In vitro gene therapy of mucopolysaccharidosis type I by lentiviral vectors.&lt;/strong&gt; Europ. J. Biochem. 269: 2764-2771, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12047386/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12047386&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1046/j.1432-1033.2002.02951.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12047386">Di Natale et al. (2002)</a> used a late-generation lentiviral vector to evaluate the usefulness of this vector system for the transfer and expression of the human IDUA cDNA in MPS I fibroblasts. They observed that the level found in normal cells and expression persisted for at least 2 months. In addition, transduced MPS I fibroblasts were capable of clearing intracellular radiolabeled glycosaminoglycan. Pulse-chase experiments on transduced fibroblasts showed that the recombinant enzyme was synthesized as a 76-kD precursor form and processed to a mature form; it was released from transduced cells and was endocytosed into a second population of untreated MPS I fibroblasts via a mannose 6-phosphate receptor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12047386" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Allogeneic bone marrow transplantation before the age of 2 years halts disease progression in Hurler syndrome and prolongs life, but many children lack a bone marrow donor. <a href="#76" class="mim-tip-reference" title="Staba, S. L., Escolar, M. L., Poe, M., Kim, Y., Martin, P. L., Szabolcs, P., Allison-Thacker, J., Wood, S., Wenger, D. A., Rubinstein, P., Hopwood, J. J., Krivit, W., Kurtzberg, J. &lt;strong&gt;Cord-blood transplants from unrelated donors in patients with Hurler&#x27;s syndrome.&lt;/strong&gt; New Eng. J. Med. 350: 1960-1969, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15128896/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15128896&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJMoa032613&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15128896">Staba et al. (2004)</a> investigated the feasibility of using cord blood transplants from unrelated donors and a myeloablative preparative regimen that did not involve total-body irradiation in young children with Hurler syndrome. Over a 7-year period, they gave 20 consecutive children with Hurler syndrome busulfan, cyclophosphamide, and antithymocyte globulin in preparation for receiving cord blood transplants from unrelated donors. Cord blood donors were discordant for up to 3 of 6 HLA markers. Neutrophil engraftment occurred a median of 24 days after transplantation. Grade II or grade III acute graft-versus-host disease occurred in 5 patients; none had extensive chronic graft-versus-host disease. Seventeen of the 20 children were alive a median of 905 days after transplantation, with complete donor chimerism and normal peripheral blood alpha-L-iduronidase activity. Transplantation improved neurocognitive performance and decreased somatic features of Hurler syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15128896" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#26" class="mim-tip-reference" title="Gentner, B., Tucci, F., Galimberti, S., Fumagalli, F., De Pellegrin, M., Silvani, P., Camesasca, C., Pontesilli, S., Darin, S., Ciotti, F., Sarzana, M., Consiglieri, G., and 36 others. &lt;strong&gt;Hematopoietic stem- and progenitor-cell gene therapy for Hurler syndrome.&lt;/strong&gt; New Eng. J. Med. 385: 1929-1940, 2021.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/34788506/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;34788506&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJMoa2106596&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="34788506">Gentner et al. (2021)</a> reported interim results of a phase 1-2 clinical trial in 8 children with Hurler syndrome to evaluate safety effectiveness of treatment with autologous hematopoietic stem and progenitor cells transduced ex vivo with an alpha-L-iduronidase-encoding lentiviral vector. The average age of the patients when treated with the gene therapy was 1.9 years, and the median follow-up was 2.1 years. The safety profile was similar to that of autologous hematopoietic stem cell transplantation. All 8 patients demonstrated sustained engraftment of gene-corrected cells and had supraphysiologic blood IUDA enzyme activity within 1 month of treatment. Patients demonstrated progressive gain of language and cognitive skills, continued motor development, improved or stable findings on brain and spine MRI, reduced joint stiffness, and normal growth. Urinary glycosaminoglycans reached normal levels at 12 months in 4 of 5 patients tested. CSF IUDA activity also increased and CSF glycosaminoglycan levels decreased. <a href="#40" class="mim-tip-reference" title="Kharbanda, S., Dvorak, C. C. &lt;strong&gt;The beginning of the end of allogeneic transplantation for Hurler syndrome? (Editorial)&lt;/strong&gt; New Eng. J. Med. 385: 2003-2004, 2021.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/34788512/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;34788512&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJMe2116020&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="34788512">Kharbanda and Dvorak (2021)</a> concluded that the gene therapy trial by <a href="#26" class="mim-tip-reference" title="Gentner, B., Tucci, F., Galimberti, S., Fumagalli, F., De Pellegrin, M., Silvani, P., Camesasca, C., Pontesilli, S., Darin, S., Ciotti, F., Sarzana, M., Consiglieri, G., and 36 others. &lt;strong&gt;Hematopoietic stem- and progenitor-cell gene therapy for Hurler syndrome.&lt;/strong&gt; New Eng. J. Med. 385: 1929-1940, 2021.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/34788506/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;34788506&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJMoa2106596&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="34788506">Gentner et al. (2021)</a> represented a step closer to a therapy that would result in complete correction of Hurler syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=34788506+34788512" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Umbilical Cord Blood Transplantation</em></strong></p><p>
<a href="#61" class="mim-tip-reference" title="Poe, M. D., Chagnon, S. L., Escolar, M. L. &lt;strong&gt;Early treatment is associated with improved cognition in Hurler syndrome.&lt;/strong&gt; Ann. Neurol. 76: 747-753, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25103575/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;25103575&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.24246&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="25103575">Poe et al. (2014)</a> reported 31 patients with Hurler syndrome who underwent umbilical cord blood transplantation between June 1997 and February 2013 and were evaluated at baseline and every 6 to 12 months thereafter. All 31 patients underwent complete neurodevelopmental evaluation (median follow-up 7.3 years, range 2-21.7) and a median of 7.0 evaluations (range 3-18 ). Younger age at transplantation was associated with improved cognitive function (p = 0.001), receptive and expressive language (p = 0.004 and p = 0.01), and adaptive behavior (p = 0.03). Early age at transplantation was a strong predictor of cognitive, language, and adaptive behavior outcomes. Children younger than 9 months at the time of transplant showed normal cognitive development. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25103575" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>Hurler syndrome is an autosomal recessive disorder (<a href="#9" class="mim-tip-reference" title="Bunge, S., Kleijer, W. J., Steglich, C., Beck, M., Schwinger, E., Gal, A. &lt;strong&gt;Mucopolysaccharidosis type I: identification of 13 novel mutations of the alpha-L-iduronidase gene.&lt;/strong&gt; Hum. Mutat. 6: 91-94, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7550242/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7550242&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.1380060119&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7550242">Bunge et al., 1995</a>; <a href="#90" class="mim-tip-reference" title="Yamagishi, A., Tomatsu, S., Fukuda, S., Uchiyama, A., Shimozawa, N., Suzuki, Y., Kondo, N., Sukegawa, K., Orii, T. &lt;strong&gt;Mucopolysaccharidosis type I: identification of common mutations that cause Hurler and Scheie syndromes in Japanese populations.&lt;/strong&gt; Hum. Mutat. 7: 23-29, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8664897/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8664897&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1098-1004(1996)7:1&lt;23::AID-HUMU3&gt;3.0.CO;2-Q&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8664897">Yamagishi et al., 1996</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8664897+7550242" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="molecularGenetics" class="mim-anchor"></a>
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<p><a href="#9" class="mim-tip-reference" title="Bunge, S., Kleijer, W. J., Steglich, C., Beck, M., Schwinger, E., Gal, A. &lt;strong&gt;Mucopolysaccharidosis type I: identification of 13 novel mutations of the alpha-L-iduronidase gene.&lt;/strong&gt; Hum. Mutat. 6: 91-94, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7550242/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7550242&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.1380060119&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7550242">Bunge et al. (1995)</a> identified 13 novel and 7 previously reported mutations of the IDUA gene, covering 88% of mutant alleles and 86% of genotypes, in a total of 29 patients with MPS I, including 5 with Hurler syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7550242" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>If the mutation rates are the same and the heterozygotes for the Hurler and Hunter syndromes have no reproductive advantage or disadvantage, the Hunter syndrome should be 1.5 times more frequent among newborns than the Hurler syndrome (<a href="#49" class="mim-tip-reference" title="McKusick, V. A. &lt;strong&gt;Relative frequency of the Hunter and Hurler syndromes.&lt;/strong&gt; New Eng. J. Med. 283: 853-854, 1970.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4989786/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4989786&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM197010152831606&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4989786">McKusick, 1970</a>). <a href="#45" class="mim-tip-reference" title="Lowry, R. B., Renwick, D. H. G. &lt;strong&gt;The relative frequency of the Hurler and Hunter syndromes. (Letter)&lt;/strong&gt; New Eng. J. Med. 284: 221-222, 1971.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4250044/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4250044&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM197101282840425&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4250044">Lowry and Renwick (1971)</a> gave estimates of the frequency of the Hurler syndrome and the Hunter syndrome in the province of British Columbia. <a href="#44" class="mim-tip-reference" title="Lowry, R. B., Applegarth, D. A., Toone, J. R., MacDonald, E., Thunem, N. Y. &lt;strong&gt;An update on the frequency of mucopolysaccharide syndromes in British Columbia.&lt;/strong&gt; Hum. Genet. 85: 389-390, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2118475/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2118475&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00206770&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2118475">Lowry et al. (1990)</a> stated that no case of the Hurler syndrome had been encountered since 1981 and no case of the Hunter syndrome since 1971. The frequency of the Hunter syndrome between 1952 and 1986 was estimated to be 1 in 110,950 live male births; the frequency of the Hurler syndrome was estimated to be 1 in 144,274 live births. Over a period of years during which he was responsible for identification of essentially all cases of mucopolysaccharidosis in Israel, <a href="#2" class="mim-tip-reference" title="Bach, G. &lt;strong&gt;Personal Communication.&lt;/strong&gt; Jerusalem, Israel 6/12/1990."None>Bach (1990)</a> found no cases of Hurler syndrome in Ashkenazim. Hurler syndrome in Ashkenazi Jews appears to be rare in the experience of others; thus, this gene may be similar to the PKU gene, which is rare in this group. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4250044+4989786+2118475" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using multiple ascertainment sources, <a href="#52" class="mim-tip-reference" title="Nelson, J., Crowhurst, J., Carey, B., Greed, L. &lt;strong&gt;Incidence of the mucopolysaccharidoses in western Australia.&lt;/strong&gt; Am. J. Med. Genet. 123A: 310-313, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14608657/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14608657&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.20314&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14608657">Nelson et al. (2003)</a> obtained an incidence rate of MPS IH in western Australia for the period 1969 to 1996 of approximately 1 in 107,000. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14608657" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>By analyzing allele and haplotype frequencies for 2 polymorphisms within the IDUA gene in the normal population and in MPS IH patients, <a href="#70" class="mim-tip-reference" title="Scott, H. S., Nelson, P. V., Cooper, A., Wraith, J. E., Hopwood, J. J., Morris, C. P. &lt;strong&gt;Mucopolysaccharidosis type I (Hurler syndrome): linkage disequilibrium indicates the presence of a major allele.&lt;/strong&gt; Hum. Genet. 88: 701-702, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1551679/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1551679&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF02265303&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1551679">Scott et al. (1992)</a> found linkage disequilibrium. One VNTR allele was present in 57% of MPS I patients as compared with 37% in the normal population. They interpreted this as indicating the presence of a major MPS I allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1551679" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Relevant to the question of the relative frequency and birth prevalence of Hurler syndrome and Hunter syndrome is the report by <a href="#62" class="mim-tip-reference" title="Poorthuis, B. J. H. M., Wevers, R. A., Kleijer, W. J., Groener, J. E. M., de Jong, J. G. N., van Weely, S., Niezen-Koning, K. E., van Diggelen, O. P. &lt;strong&gt;The frequency of lysosomal storage diseases in The Netherlands.&lt;/strong&gt; Hum. Genet. 105: 151-156, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10480370/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10480370&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s004399900075&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10480370">Poorthuis et al. (1999)</a> on the frequency of lysosomal storage diseases in the Netherlands. MPS I had the highest calculated birth prevalence of 1.19 per 100,000 (25% of all cases of MPS diagnosed); the birth prevalence of MPS II was 0.67 per 100,000 (1.30 per 100,000 male live births). (The second most frequent mucopolysaccharidosis was MPS IIIA (Sanfilippo syndrome type A; <a href="/entry/252900">252900</a>) with an estimated birth prevalence of 1.16 per 100,000.) <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10480370" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a group of 46 European patients with MPS I, <a href="#10" class="mim-tip-reference" title="Bunge, S., Kleijer, W. J., Steglich, C., Beck, M., Zuther, C., Morris, C. P., Schwinger, E., Hopwood, J. J., Scott, H. S., Gal, A. &lt;strong&gt;Mucopolysaccharidosis type I: identification of 8 novel mutations and determination of the frequency of the two common alpha-L-iduronidase mutations (W402X and Q70X) among European patients.&lt;/strong&gt; Hum. Molec. Genet. 3: 861-866, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7951228/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7951228&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/3.6.861&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7951228">Bunge et al. (1994)</a> found that the 2 common nonsense mutations, W402X (<a href="/entry/252800#0001">252800.0001</a>) and Q70X (<a href="/entry/252800#0002">252800.0002</a>), were identified in 37% and 35% of mutant alleles, respectively. Considerable differences were seen in the frequency of these 2 mutations in patients from Norway and Finland as compared with other European countries, mainly the Netherlands and Germany. In Scandinavia, W402X and Q70X accounted for 17% and 62% of the MPS I alleles, respectively, while in other European countries W402X was about 2.5 times more frequent (48%) than Q70X (19%). <a href="#10" class="mim-tip-reference" title="Bunge, S., Kleijer, W. J., Steglich, C., Beck, M., Zuther, C., Morris, C. P., Schwinger, E., Hopwood, J. J., Scott, H. S., Gal, A. &lt;strong&gt;Mucopolysaccharidosis type I: identification of 8 novel mutations and determination of the frequency of the two common alpha-L-iduronidase mutations (W402X and Q70X) among European patients.&lt;/strong&gt; Hum. Molec. Genet. 3: 861-866, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7951228/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7951228&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/3.6.861&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7951228">Bunge et al. (1994)</a> also described 8 novel mutations, including 4 missense mutations, 1 nonsense mutation, 1 insertion of 2 basepairs, and 2 deletions of 1 and 12 basepairs. All the patients in this study had a typical, severe form of the disease, MPS IH, with marked skeletal changes, hepatosplenomegaly, and mental retardation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951228" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#90" class="mim-tip-reference" title="Yamagishi, A., Tomatsu, S., Fukuda, S., Uchiyama, A., Shimozawa, N., Suzuki, Y., Kondo, N., Sukegawa, K., Orii, T. &lt;strong&gt;Mucopolysaccharidosis type I: identification of common mutations that cause Hurler and Scheie syndromes in Japanese populations.&lt;/strong&gt; Hum. Mutat. 7: 23-29, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8664897/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8664897&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1098-1004(1996)7:1&lt;23::AID-HUMU3&gt;3.0.CO;2-Q&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8664897">Yamagishi et al. (1996)</a> defined the IDUA mutations in 19 Japanese MPS I patients, including 2 pairs of sibs, with various clinical phenotypes; Hurler syndrome, 6 cases; Hurler/Scheie syndrome, 7 cases; Scheie syndrome, 6 cases. Two common mutations accounted for 42% of the 38 alleles in these patients. One was a novel 5-bp insertion between the T at nucleotide 704 and the C at nucleotide 705 (704ins5; <a href="/entry/252800#0014">252800.0014</a>), which was seen only in the Japanese population. The other was a missense mutation, R89Q (<a href="/entry/252800#0015">252800.0015</a>), which is seen also in Caucasians, although uncommonly. No Japanese patient was found to carry the W402X or Q70X alleles, the 2 most common MPS I mutations in Caucasians. Homozygosity for the 704ins5 mutation was associated with a severe phenotype; homozygosity for the R89Q mutation was associated with a mild phenotype. Compound heterozygosity for these 2 mutations produced an intermediate phenotype. Haplotype analysis using polymorphisms linked to IDUA locus demonstrated that each of these 2 common mutations occurred on a different specific haplotype, suggesting that individuals with each of these common mutations derived from a common founder. The mild-intermediate-severe phenotypic relationships of the 2 common Japanese mutations fulfill the prediction of <a href="#48" class="mim-tip-reference" title="McKusick, V. A., Howell, R. R., Hussels, I. E., Neufeld, E. F., Stevenson, R. E. &lt;strong&gt;Allelism, nonallelism and genetic compounds among the mucopolysaccharidoses.&lt;/strong&gt; Lancet 299: 993-996, 1972. Note: Originally Volume I.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4112371/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4112371&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(72)91159-2&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4112371">McKusick et al. (1972)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8664897+4112371" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#68" class="mim-tip-reference" title="Scott, H. S., Bunge, S., Gal, A., Clarke, L. A., Morris, C. P., Hopwood, J. J. &lt;strong&gt;Molecular genetics of mucopolysaccharidosis type I: diagnostic, clinical, and biological implications.&lt;/strong&gt; Hum. Mutat. 6: 288-302, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8680403/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8680403&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.1380060403&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8680403">Scott et al. (1995)</a> indicated that a total of 46 mutations in the IDUA gene had been defined: 8 nonsense mutations, 21 missense mutations, 3 splice site mutations, and 14 minor deletions and/or insertions. Furthermore, 30 polymorphisms or nonpathogenic sequence variants had been defined, including 7 amino acid substitutions. Among patients of European origin, there were 2 major mutations associated with MPS I: W402X and Q70X, which together accounted for between 24% (Italian) and 84% (Scandinavian) of the MPS I alleles in patients of European origin. Different alleles predominate in Japanese patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8680403" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#25" class="mim-tip-reference" title="Gatti, R., DiNatale, P., Villani, G. R. D., Filocamo, M., Muller, V., Guo, X.-H., Nelson, P. V., Scott, H. S., Hopwood, J. J. &lt;strong&gt;Mutations among Italian mucopolysaccharidosis type I patients.&lt;/strong&gt; J. Inherit. Metab. Dis. 20: 803-806, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9427149/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9427149&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1023/a:1005323918923&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9427149">Gatti et al. (1997)</a> screened for IDUA mutations in 27 Italian patients with MPS I. Mutations were found in 18 patients, with 28 alleles identified. The 2 most common mutations in northern Europeans, W402X and Q70X, accounted for 11 and 13% of the alleles, respectively. The P533R (<a href="/entry/252800#0003">252800.0003</a>) mutation accounted for 11% of the 54 alleles and seemed to be confined to Sicily; the frequency of P533R was 3% in a British/Australian study. Two P533R homozygotes were stated to have an intermediate phenotype in one and a mild phenotype in a second. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9427149" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#43" class="mim-tip-reference" title="Lin, H.-Y., Lin, S.-P., Chuang, C.-K., Niu, D.-M., Chen, M.-R., Tsai, F.-J., Chao, M.-C., Chiu, P.-C., Lin, S.-J., Tsai, L.-P., Hwu, W.-L., Lin, J.-L. &lt;strong&gt;Incidence of the mucopolysaccharidoses in Taiwan, 1984-2004.&lt;/strong&gt; Am. J. Med. Genet. 149A: 960-964, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19396827/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19396827&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.32781&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19396827">Lin et al. (2009)</a> analyzed the incidence of MPS in Taiwan between 1984 and 2004 and found that the combined birth incidence for all MPS cases was 2.04 per 100,000 live births. MPS II (Hunter syndrome) had the highest calculated birth incidence (1.07 per 100,000 live births), comprising 52% of all MPS cases diagnosed. The birth incidences of MPS I, III (Sanfilippo syndrome), IV (Morquio syndrome), and VI (Maroteaux-Lamy syndrome) were 0.11, 0.39, 0.33, and 0.14 per 100,000 live births, respectively, and accounted for 6%, 19%, 16%, and 7% of all MPS, respectively. Although the overall incidence of MPS in Taiwan was consistent with reports from Western populations, <a href="#43" class="mim-tip-reference" title="Lin, H.-Y., Lin, S.-P., Chuang, C.-K., Niu, D.-M., Chen, M.-R., Tsai, F.-J., Chao, M.-C., Chiu, P.-C., Lin, S.-J., Tsai, L.-P., Hwu, W.-L., Lin, J.-L. &lt;strong&gt;Incidence of the mucopolysaccharidoses in Taiwan, 1984-2004.&lt;/strong&gt; Am. J. Med. Genet. 149A: 960-964, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19396827/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19396827&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.32781&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19396827">Lin et al. (2009)</a> noted that in contrast to reports of a higher incidence of MPS I in most Western populations, their study showed a higher incidence of MPS II in Taiwan. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19396827" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#80" class="mim-tip-reference" title="Vazna, A., Beesley, C., Berna, L., Stolnaja, L., Myskova, H., Bouckova, M., Vlaskova, H., Poupetova, H., Zeman, J., Magner, M., Hlavata, A., Winchester, B., Hrebicek, M., Dvorakova, L. &lt;strong&gt;Mucopolysaccharidosis type I in 21 Czech and Slovak patients: mutation analysis suggests a functional importance of C-terminus of the IDUA protein.&lt;/strong&gt; Am. J. Med. Genet. 149A: 965-974, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19396826/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19396826&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=19396826[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.32812&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19396826">Vazna et al. (2009)</a> reported that 21 Czech and Slovak patients had been diagnosed with MPS I over the past 30 years, 16 with a severe clinical presentation (Hurler syndrome), 2 less severe (Scheie syndrome), and 3 of intermediate severity (Hurler-Scheie syndrome). Mutation analysis in 22 patients showed a high prevalence of the null mutations W402X and Q70X (12 and 7 alleles, respectively). The authors stated that missense mutations located predominantly in the hydrophobic core of the enzyme were associated with the severe phenotype, whereas missense mutations localized to the surface of the enzyme were usually associated with the attenuated phenotypes. Mutations in the 130 C-terminal amino acids led to clinical manifestations, indicating functional importance of the C terminus of the IDUA protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19396826" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#39" class="mim-tip-reference" title="Khan, S. A., Peracha, H., Ballhausen, D., Wiesbauer, A., Rohrbach, M., Gautschi, M., Mason, R. W., Giugliani, R., Suzuki, Y., Orii, K. E., Orii, T., Tomatsu, S. &lt;strong&gt;Epidemiology of mucopolysaccharidoses.&lt;/strong&gt; Molec. Genet. Metab. 121: 227-240, 2017.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/28595941/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;28595941&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=28595941[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2017.05.016&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="28595941">Khan et al. (2017)</a> analyzed the epidemiology of the mucopolysaccharidoses in Japan and Switzerland and compared them to similar data from other countries. Data for Japan was collected between 1982 and 2009, and 467 cases with MPS were identified. The combined birth prevalence was 1.53 per 100,000 live births. The highest birth prevalence was 0.84 for MPS II (<a href="/entry/309900">309900</a>), accounting for 55% of all MPS. MPS I, III (see <a href="/entry/252900">252900</a>), and IV (see <a href="/entry/253000">253000</a>) accounted for 15%, 16%, and 10%, respectively. MPS VI (<a href="/entry/253200">253200</a>) and VII (<a href="/entry/253220">253220</a>) were more rare and accounted for 1.7% and 1.3%, respectively. A retrospective epidemiologic data collection was performed in Switzerland between 1975 and 2008 (34 years), and 41 living MPS patients were identified. The combined birth prevalence was 1.56 per 100,000 live births. The highest birth prevalence was 0.46 for MPS II, accounting for 29% of all MPS. MPS I, III, and IV accounted for 12%, 24%, and 24%, respectively. As seen in the Japanese population, MPS VI and VII were more rare and accounted for 7.3% and 2.4%, respectively. The high birth prevalence of MPS II in Japan was comparable to that seen in other East Asian countries where this MPS accounted for approximately 50% of all forms of MPS. Birth prevalence was also similar in some European countries (Germany, Northern Ireland, Portugal and the Netherlands) although the prevalence of other forms of MPS was also reported to be higher in these countries. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28595941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#46" class="mim-tip-reference" title="Matte, U., Leistner, S., Lima, L., Schwartz, I., Giugliani, R. &lt;strong&gt;Unique frequency of known mutations in Brazilian MPS I patients.&lt;/strong&gt; Am. J. Med. Genet. 90: 108-109, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10607946/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10607946&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(sici)1096-8628(20000117)90:2&lt;108::aid-ajmg3&gt;3.0.co;2-y&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10607946">Matte et al. (2000)</a> analyzed 24 Brazilian MPS I patients for 10 known mutations in the IDUA gene. Only 37% of genotypes and 54% of the alleles were defined using this method, demonstrating a low frequency of these 10 mutations in this population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10607946" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="animalModel" class="mim-anchor"></a>
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimAnimalModelToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
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<strong>Animal Model</strong>
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<p><a href="#32" class="mim-tip-reference" title="Haskins, M. E., Jezyk, P. F., Desnick, R. J., McDonaugh, S. K., Patterson, D. F. &lt;strong&gt;Alpha-L-iduronidase deficiency in a cat: a model of mucopolysaccharidosis I.&lt;/strong&gt; Pediat. Res. 13: 1294-1297, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/117422/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;117422&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/00006450-197911000-00018&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="117422">Haskins et al. (1979)</a> described a model of MPS I in the cat, and <a href="#74" class="mim-tip-reference" title="Shull, R. M., Munger, R. J., Spellacy, E., Hall, C. W., Constantopoulos, G., Neufeld, E. F. &lt;strong&gt;Canine alpha-L-iduronidase deficiency: a model of mucopolysaccharidosis I.&lt;/strong&gt; Am. J. Path. 109: 244-248, 1982.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6215865/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6215865&lt;/a&gt;]" pmid="6215865">Shull et al. (1982)</a> and <a href="#75" class="mim-tip-reference" title="Spellacy, E., Shull, R. M., Constantopoulos, G., Neufeld, E. F. &lt;strong&gt;A canine model of human alpha-L-iduronidase deficiency.&lt;/strong&gt; Proc. Nat. Acad. Sci. 80: 6091-6095, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6412235/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6412235&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.80.19.6091&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6412235">Spellacy et al. (1983)</a> described a model in the dog. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=117422+6215865+6412235" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#73" class="mim-tip-reference" title="Shull, R. M., Kakkis, E. D., McEntee, M. F., Kania, S. A., Jonas, A. J., Neufeld, E. F. &lt;strong&gt;Enzyme replacement in a canine model of Hurler syndrome.&lt;/strong&gt; Proc. Nat. Acad. Sci. 91: 12937-12941, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7809150/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7809150&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.91.26.12937&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7809150">Shull et al. (1994)</a> reported results of enzyme replacement in the canine model. Recombinant human alpha-L-iduronidase, purified to apparent homogeneity from secretions of a stably transfected Chinese hamster ovary cell line, was administered intravenously to homozygous affected animals in doses of approximately 1 mg. The enzyme rapidly disappeared from the circulation in a biphasic manner, with a half-life of 0.9 and 19 min, respectively, and was taken up primarily by the liver. Biopsy of the liver before and after a trial of 7 doses administered over 12 days showed remarkable resolution of lysosomal storage in both hepatocytes and Kupffer cells. After weekly administration of enzyme to 3 affected animals over a period of 3 months, the level of enzyme was about normal in liver and spleen, lower but significant in kidney and lung, and barely detectable (0-5% of normal) in brain, heart valve, myocardium, cartilage, and cornea. Light and electron microscopic examination showed normalization of lysosomal storage in liver, spleen, and kidney glomeruli, but there was no improvement in brain, heart valves, or cornea. The treated dogs developed complement-activating antibodies against the enzyme but clinical symptoms could be avoided by slow infusion of enzyme and premedication with antihistamine and sedative. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7809150" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#29" class="mim-tip-reference" title="Grosson, C. L. S., MacDonald, M. E., Duyao, M. P., Ambrose, C. M., Roffler-Tarlov, S., Gusella, J. F. &lt;strong&gt;Synteny conservation of the Huntington&#x27;s disease gene and surrounding loci on mouse chromosome 5.&lt;/strong&gt; Mammalian Genome 5: 424-428, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7919654/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7919654&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00357002&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7919654">Grosson et al. (1994)</a> mapped the homologous locus in the mouse, Idua, to chromosome 5 in a continuous linkage group that included the homolog of the Huntington disease gene. <a href="#13" class="mim-tip-reference" title="Clarke, L. A., Russell, C. S., Pownall, S., Warrington, C. L., Borowski, A., Dimmick, J. E., Toone, J., Jirik, F. R. &lt;strong&gt;Murine mucopolysaccharidosis type I: targeted disruption of the murine alpha-L-iduronidase gene.&lt;/strong&gt; Hum. Molec. Genet. 6: 503-511, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9097952/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9097952&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/6.4.503&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9097952">Clarke et al. (1997)</a> created a mouse strain completely deficient in iduronidase by targeted disruption of the Idua gene. <a href="#64" class="mim-tip-reference" title="Russell, C., Hendson, G., Jevon, G., Matlock, T., Yu, J., Aklujkar, M., Ng, K.-Y., Clarke, L. A. &lt;strong&gt;Murine MPS I: insights into the pathogenesis of Hurler syndrome.&lt;/strong&gt; Clin. Genet. 53: 349-361, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9660052/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9660052&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1998.tb02745.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9660052">Russell et al. (1998)</a> reported on the long-term clinical, biochemical, and pathologic course of MPS I in mice, with emphasis on the skeletal and CNS manifestations. Affected mice showed a progressive clinical course with the development of coarse features, altered growth characteristics, and a shortened life span. Progressive lysosomal accumulation was seen in all tissues. Skeletal manifestations represented the earliest clinical findings, with histologic analysis of growth plate and cortical bone revealing evidence of significant early pathology. Analysis of the CNS showed progressive neuronal loss within the cerebellum. In addition, brain tissue from MPS I mice showed increased levels of GM2 and GM3 gangliosides. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9660052+9097952+7919654" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#57" class="mim-tip-reference" title="Ohmi, K., Greenberg, D. S., Rajavel, K. S., Ryazantsev, S., Li, H. H., Neufeld, E. F. &lt;strong&gt;Activated microglia in cortex of mouse models of mucopolysaccharidoses I and IIIB.&lt;/strong&gt; Proc. Nat. Acad. Sci. 100: 1902-1907, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12576554/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12576554&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=12576554[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.252784899&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12576554">Ohmi et al. (2003)</a> studied the brain of mouse models of MPS I and MPS IIIB (<a href="/entry/252920">252920</a>) in connection with previous evidence of microglial involvement in the pathogenesis of mucopolysaccharidoses. The studies showed an inflammatory component of brain disease in both of these forms of MPS. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12576554" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Immune responses can interfere with the effective use of enzyme replacement in treatment of Hurler syndrome and other genetic deficiencies. To address this problem, <a href="#37" class="mim-tip-reference" title="Kakkis, E., Lester, T., Yang, R., Tanaka, C., Anand, V., Lemontt, J., Peinovich, M., Passage, M. &lt;strong&gt;Successful induction of immune tolerance to enzyme replacement therapy in canine mucopolysaccharidosis I.&lt;/strong&gt; Proc. Nat. Acad. Sci. 101: 829-834, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14715900/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14715900&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=14715900[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.0305480101&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14715900">Kakkis et al. (2004)</a> studied methods of immune tolerance used in canine organ transplantation research, extending it to the use of soluble proteins in therapeutics. They developed a tolerization regimen for use in a canine model of MPS I. The tolerizing regimen consisted of a limited 60-day course of cyclosporin A and azathioprine combined with weekly intravenous infusions of low-dose recombinant human alpha-L-iduronidase. The experimental dogs tolerized with this regimen maintained a reduced immune response for up to 6 months despite weekly therapeutic doses of enzyme in the absence of immunosuppressive drugs. Successful tolerization depended on high plasma levels of cyclosporin A combined with azathioprine. In addition, the induction of tolerance may require mannose 6-phosphate receptor-mediated uptake because alpha-L-iduronidase and alpha-glucosidase (<a href="/entry/606800">606800</a>) induced tolerance with the drug regimen whereas ovalbumin and dephosphorylated alpha-L-iduronidase did not. <a href="#37" class="mim-tip-reference" title="Kakkis, E., Lester, T., Yang, R., Tanaka, C., Anand, V., Lemontt, J., Peinovich, M., Passage, M. &lt;strong&gt;Successful induction of immune tolerance to enzyme replacement therapy in canine mucopolysaccharidosis I.&lt;/strong&gt; Proc. Nat. Acad. Sci. 101: 829-834, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14715900/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;14715900&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=14715900[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.0305480101&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14715900">Kakkis et al. (2004)</a> suggested that this approach should be applicable to the treatment of other lysosomal storage disorders and that the strategy might be used for reduction in antibodies associated with autoimmune disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14715900" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#92" class="mim-tip-reference" title="Zheng, Y., Rozengurt, N., Ryazantsev, S., Kohn, D. B., Satake, N., Neufeld, E. F. &lt;strong&gt;Treatment of the mouse model of mucopolysaccharidosis I with retrovirally transduced bone marrow.&lt;/strong&gt; Molec. Genet. Metab. 79: 233-244, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12948739/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12948739&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s1096-7192(03)00116-1&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12948739">Zheng et al. (2003)</a> transduced bone marrow from Idua knockout male mice with human IDUA cDNA in an MND vector and transplanted it into 6-to-8-week-old, lethally irradiated female Idua -/- mice. Sham-treated mice received Idua -/- bone marrow that was either unmodified or transduced with enhanced GFP. Transplantation of unmodified wildtype bone marrow was effective in reducing storage in liver and spleen but not in kidney or brain. The level of alpha-L-iduronidase activity achieved by transplantation of IDUA-transduced bone marrow varied greatly between experiments. Even modest activity resulted in correction of pathology of kidney, bladder epithelium, fibrocartilage, choroid plexus, and thalamus, as seen by light microscopy; electron microscopy showed the presence of some normal neurons in the cortex. The partial correction of brain pathology was attributed to migration of donor hematopoietic cells, demonstrated by the presence of the Y chromosome and of normal microglia in the brain of mice receiving IDUA cDNA. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12948739" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="Desmaris, N., Verot, L., Puech, J. P., Caillaud, C., Vanier, M. T., Heard, J. M. &lt;strong&gt;Prevention of neuropathology in the mouse model of Hurler syndrome.&lt;/strong&gt; Ann. Neurol. 56: 68-76, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15236403/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15236403&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.20150&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15236403">Desmaris et al. (2004)</a> used adenoviral vectors (AAV2 and AAV5) to inject human IDUA into the right putamen in a mouse model of MPS I. After a single injection, enzyme activity was detected throughout the brain, including the contralateral hemisphere, the cerebellum, and the brainstem. In the treated mouse brains, neuropathologic examination showed decreased ganglioside accumulation as well as evidence suggesting reversal of disease pathology in some areas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15236403" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Ciron, C., Desmaris, N., Colle, M.-A., Raoul, S., Joussemet, B., Verot, L., Ausseil, J., Froissart, R., Roux, F., Cherel, Y., Ferry, N., Lajat, Y., Schwartz, B., Vanier, M.-T., Maire, I., Tardieu, M., Moullier, P., Heard, J.-M. &lt;strong&gt;Gene therapy of the brain in the dog model of Hurler&#x27;s syndrome.&lt;/strong&gt; Ann. Neurol. 60: 204-213, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16718701/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16718701&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.20870&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16718701">Ciron et al. (2006)</a> reported stereotactic adenoviral-mediated injection of human IDUA into the brains of dogs with MPS1. The dogs were treated between 3 and 4.8 months of age after symptoms had developed. Neuropathologic analysis showed broad and efficient IDUA delivery in the brain, reduced pathology, and improvement of biochemical disease markers in most areas. Clinical improvement could not be assessed. Dogs receiving partial immunosuppression treatment developed a subacute encephalitis with neuroinflammation in the brain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16718701" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="history" class="mim-anchor"></a>
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<strong>History</strong>
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<p>In discussing Otto Ullrich, <a href="#85" class="mim-tip-reference" title="Wiedemann, H.-R. &lt;strong&gt;Otto Ullrich and his syndromes.&lt;/strong&gt; Am. J. Med. Genet. 41: 128-133, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1951453/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1951453&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320410131&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1951453">Wiedemann (1991)</a> gave an extensive account of Ullrich's teacher, Meinhard von Pfaundler, professor of pediatrics at Munich, whose name is often combined with that of Gertrud Hurler. Hurler was a pediatrician who worked for many years in Munich. <a href="#85" class="mim-tip-reference" title="Wiedemann, H.-R. &lt;strong&gt;Otto Ullrich and his syndromes.&lt;/strong&gt; Am. J. Med. Genet. 41: 128-133, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1951453/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1951453&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320410131&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1951453">Wiedemann (1991)</a> commented that 'Anglo-American influence may even cause our young West-German physicians to mispronounce it as if it were spelled 'Hoerler'' (i.e., with an o umlaut rather than a u). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1951453" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Bernal, J. E., Briceno, I. &lt;strong&gt;Genetic and other diseases in the pottery of Tumaco-La Tolita culture in Colombia-Ecuador.&lt;/strong&gt; Clin. Genet. 70: 188-191, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16922718/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16922718&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.2006.00670.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16922718">Bernal and Briceno (2006)</a> examined pottery artifacts from the Tumaco-La Tolita culture, which existed on the border of present-day Colombia and Ecuador approximately 2,500 years ago, and described 3 figurines showing coarse facies, prominent eyebrows, wide mouth, and umbilical hernia, resembling mucopolysaccharidosis IH. <a href="#5" class="mim-tip-reference" title="Bernal, J. E., Briceno, I. &lt;strong&gt;Genetic and other diseases in the pottery of Tumaco-La Tolita culture in Colombia-Ecuador.&lt;/strong&gt; Clin. Genet. 70: 188-191, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16922718/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16922718&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.2006.00670.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16922718">Bernal and Briceno (2006)</a> believed these artifacts to be among the earliest artistic representations of disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16922718" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Unclassified Mucopolysaccharidosis</em></strong></p><p>
<a href="#8" class="mim-tip-reference" title="Brown, S. I., Kuwabara, T. &lt;strong&gt;Peripheral corneal opacification and skeletal deformities: a newly recognized acid mucopolysaccharidosis simulating rheumatoid arthritis.&lt;/strong&gt; Arch. Ophthal. 83: 667-677, 1970.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4246484/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4246484&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archopht.1970.00990030667001&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4246484">Brown and Kuwabara (1970)</a> observed 2 sisters, aged 5 and 13 years, with Hurler-like facies, swollen fingers, dwarfed stature, severe progressive joint destruction and peculiar progressive peripheral annular corneal opacification. The parents were Puerto Rican first cousins. Fibroblasts showed metachromasia and increased mucopolysaccharide. Urinary mucopolysaccharide was normal. High doses of vitamins seemed to be beneficial. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4246484" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#66" class="mim-tip-reference" title="Scott, C. R., Lagunoff, D., Pritzl, P. &lt;strong&gt;A mucopolysaccharide storage disease with involvement of the renal glomerular epithelium.&lt;/strong&gt; Am. J. Med. 54: 549-556, 1973.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4348719/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4348719&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0002-9343(73)90053-3&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4348719">Scott et al. (1973)</a> described a male child who had mucopolysacchariduria, mental retardation, 'dysostosis multiplex' and appearance similar to that of a mucopolysaccharidosis. Death occurred at 47 months from pneumonia. The reticuloendothelial system remained free of mucopolysaccharide although accumulations were found in the perichondrium, coronary arteries, aorta, and glomerular epithelial cells of the kidney. Lipid accumulated in peripheral neurons but not in central neurons. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4348719" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>See Also:</strong>
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<a href="#Bach1993" class="mim-tip-reference" title="Bach, G., Moskowitz, S. M., Tieu, P. T., Matynia, A., Neufeld, E. F. &lt;strong&gt;Molecular analysis of Hurler syndrome in Druze and Muslim Arab patients in Israel: multiple allelic mutations of the IDUA gene in a small geographic area.&lt;/strong&gt; Am. J. Hum. Genet. 53: 330-338, 1993.">Bach et al. (1993)</a>; <a href="#Menon1992" class="mim-tip-reference" title="Menon, K. P., Tieu, P. T., Neufeld, E. F. &lt;strong&gt;Architecture of the canine IDUA gene and mutation underlying canine mucopolysaccharidosis I.&lt;/strong&gt; Genomics 14: 763-768, 1992.">Menon et al. (1992)</a>; <a href="#Scott1993" class="mim-tip-reference" title="Scott, H. S., Litjens, T., Nelson, P. V., Thompson, P. R., Brooks, D. A., Hopwood, J. J., Morris, C. P. &lt;strong&gt;Identification of mutations in the alpha-L-iduronidase gene (IDUA) that cause Hurler and Scheie syndromes.&lt;/strong&gt; Am. J. Hum. Genet. 53: 973-986, 1993.">Scott et al. (1993)</a>
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<a id="1" class="mim-anchor"></a>
<a id="Bach1993" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bach, G., Moskowitz, S. M., Tieu, P. T., Matynia, A., Neufeld, E. F.
<strong>Molecular analysis of Hurler syndrome in Druze and Muslim Arab patients in Israel: multiple allelic mutations of the IDUA gene in a small geographic area.</strong>
Am. J. Hum. Genet. 53: 330-338, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8328452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8328452</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8328452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Bach1990" class="mim-anchor"></a>
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<p class="mim-text-font">
Bach, G.
<strong>Personal Communication.</strong>
Jerusalem, Israel 6/12/1990.
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<a id="Beesley2001" class="mim-anchor"></a>
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Beesley, C. E., Meaney, C. A., Greenland, G., Adams, V., Vellodi, A., Young, E. P., Winchester, B. G.
<strong>Mutational analysis of 85 mucopolysaccharidosis type I families: frequency of known mutations, identification of 17 novel mutations and in vitro expression of missense mutations.</strong>
Hum. Genet. 109: 503-511, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11735025/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11735025</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11735025" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/s004390100606" target="_blank">Full Text</a>]
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<a id="Belani1993" class="mim-anchor"></a>
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Belani, K. G., Krivit, W., Carpenter, B. L. M., Braulin, E., Buckley, J. J., Liao, J.-C., Floyd, T., Leonard, A. S., Summers, C. G., Levine, S., Whitley, C. B.
<strong>Children with mucopolysaccharidosis: perioperative care, morbidity, mortality, and new findings.</strong>
J. Pediat. Surg. 28: 403-410, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8468655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8468655</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8468655" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0022-3468(93)90240-l" target="_blank">Full Text</a>]
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<a id="Bernal2006" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bernal, J. E., Briceno, I.
<strong>Genetic and other diseases in the pottery of Tumaco-La Tolita culture in Colombia-Ecuador.</strong>
Clin. Genet. 70: 188-191, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16922718/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16922718</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16922718" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1399-0004.2006.00670.x" target="_blank">Full Text</a>]
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<a id="Braunlin2019" class="mim-anchor"></a>
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Braunlin, E., Miettunen, K., Lund, T., Luquette, M., Orchard, P.
<strong>Hematopoietic cell transplantation for severe MPS I in the first six months of life: the heart of the matter.</strong>
Molec. Genet. Metab. 126: 117-120, 2019.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30503158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30503158</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30503158" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.ymgme.2018.11.007" target="_blank">Full Text</a>]
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<a id="Brooks1992" class="mim-anchor"></a>
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Brooks, D. A., Harper, G. S., Gibson, G. L., Ashton, L. J., Taylor, J. A., McCourt, P. A. G., Freeman, C., Clements, P. R., Hoffman, J. W., Hopwood, J. J.
<strong>Hurler syndrome: a patient with abnormally high levels of alpha-L-iduronidase protein.</strong>
Biochem. Med. Metab. Biol. 47: 211-220, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1627351/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1627351</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1627351" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0885-4505(92)90028-w" target="_blank">Full Text</a>]
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<a id="Brown1970" class="mim-anchor"></a>
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Brown, S. I., Kuwabara, T.
<strong>Peripheral corneal opacification and skeletal deformities: a newly recognized acid mucopolysaccharidosis simulating rheumatoid arthritis.</strong>
Arch. Ophthal. 83: 667-677, 1970.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4246484/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4246484</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4246484" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archopht.1970.00990030667001" target="_blank">Full Text</a>]
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<a id="Bunge1995" class="mim-anchor"></a>
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Bunge, S., Kleijer, W. J., Steglich, C., Beck, M., Schwinger, E., Gal, A.
<strong>Mucopolysaccharidosis type I: identification of 13 novel mutations of the alpha-L-iduronidase gene.</strong>
Hum. Mutat. 6: 91-94, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7550242/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7550242</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7550242" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/humu.1380060119" target="_blank">Full Text</a>]
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<a id="Bunge1994" class="mim-anchor"></a>
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Bunge, S., Kleijer, W. J., Steglich, C., Beck, M., Zuther, C., Morris, C. P., Schwinger, E., Hopwood, J. J., Scott, H. S., Gal, A.
<strong>Mucopolysaccharidosis type I: identification of 8 novel mutations and determination of the frequency of the two common alpha-L-iduronidase mutations (W402X and Q70X) among European patients.</strong>
Hum. Molec. Genet. 3: 861-866, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7951228/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7951228</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7951228" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/3.6.861" target="_blank">Full Text</a>]
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<a id="Caruso1986" class="mim-anchor"></a>
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Caruso, R. C., Kaiser-Kupfer, M. I., Muenzer, J., Ludwig, I. H., Zasloff, M. A., Mercer, P. A.
<strong>Electroretinographic findings in the mucopolysaccharidoses.</strong>
Ophthalmology 93: 1612-1616, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3101020/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3101020</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3101020" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0161-6420(86)33537-1" target="_blank">Full Text</a>]
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<a id="Ciron2006" class="mim-anchor"></a>
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Ciron, C., Desmaris, N., Colle, M.-A., Raoul, S., Joussemet, B., Verot, L., Ausseil, J., Froissart, R., Roux, F., Cherel, Y., Ferry, N., Lajat, Y., Schwartz, B., Vanier, M.-T., Maire, I., Tardieu, M., Moullier, P., Heard, J.-M.
<strong>Gene therapy of the brain in the dog model of Hurler's syndrome.</strong>
Ann. Neurol. 60: 204-213, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16718701/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16718701</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16718701" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ana.20870" target="_blank">Full Text</a>]
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<a id="Clarke1997" class="mim-anchor"></a>
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Clarke, L. A., Russell, C. S., Pownall, S., Warrington, C. L., Borowski, A., Dimmick, J. E., Toone, J., Jirik, F. R.
<strong>Murine mucopolysaccharidosis type I: targeted disruption of the murine alpha-L-iduronidase gene.</strong>
Hum. Molec. Genet. 6: 503-511, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9097952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9097952</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9097952" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/hmg/6.4.503" target="_blank">Full Text</a>]
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<a id="Cleary1995" class="mim-anchor"></a>
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[<a href="https://doi.org/10.1126/science.149.3687.987" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ana.20150" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1046/j.1432-1033.2002.02951.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0022-3476(89)80565-7" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1126/science.162.3853.570" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1056/NEJMoa2106596" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF02338973" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00357002" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0076-6879(78)50048-7" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00711520" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.ophtha.2015.01.015" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0140-6736(83)91168-6" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.0305480101" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1056/NEJMe2116020" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1056/NEJM197101282840425" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ana.24246" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s004399900075" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0002-9149(76)90468-9" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/j.1399-0004.1998.tb02745.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1172/JCI113317" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0002-9343(73)90053-3" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/humu.1380060403" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF02265303" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1097/00005792-198807000-00002" target="_blank">Full Text</a>]
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<strong>A nonpathologic allele (IW) for low alpha-L-iduronidase enzyme activity vis-a-vis prenatal diagnosis of Hurler syndrome.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3118714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3118714</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3118714" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320280136" target="_blank">Full Text</a>]
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<a id="Wiedemann1991" class="mim-anchor"></a>
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Wiedemann, H.-R.
<strong>Otto Ullrich and his syndromes.</strong>
Am. J. Med. Genet. 41: 128-133, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1951453/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1951453</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1951453" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320410131" target="_blank">Full Text</a>]
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Wiesmann, U. N., Neufeld, E. F.
<strong>Scheie and Hurler syndromes: apparent identity of the biochemical defect.</strong>
Science 169: 72-74, 1970.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4246082/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4246082</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4246082" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1126/science.169.3940.72" target="_blank">Full Text</a>]
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Wippermann, C.-F., Beck, M., Schranz, D., Huth, R., Michel-Behnke, I., Jungst, B.-K.
<strong>Mitral and aortic regurgitation in 84 patients with mucopolysaccharidoses.</strong>
Europ. J. Pediat. 154: 98-101, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7720756/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7720756</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7720756" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF01991908" target="_blank">Full Text</a>]
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<a id="Wraith1990" class="mim-anchor"></a>
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Wraith, J. E., Alani, S. M.
<strong>Carpal tunnel syndrome in the mucopolysaccharidoses and related disorders.</strong>
Arch. Dis. Child. 65: 962-963, 1990.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2121106/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2121106</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2121106" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/adc.65.9.962" target="_blank">Full Text</a>]
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<a id="Wraith1987" class="mim-anchor"></a>
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Wraith, J. E., Rogers, J. G., Danks, D. M.
<strong>The mucopolysaccharidoses.</strong>
Aust. Paediat. J. 23: 329-334, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3124802/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3124802</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3124802" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1440-1754.1987.tb00284.x" target="_blank">Full Text</a>]
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Yamagishi, A., Tomatsu, S., Fukuda, S., Uchiyama, A., Shimozawa, N., Suzuki, Y., Kondo, N., Sukegawa, K., Orii, T.
<strong>Mucopolysaccharidosis type I: identification of common mutations that cause Hurler and Scheie syndromes in Japanese populations.</strong>
Hum. Mutat. 7: 23-29, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8664897/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8664897</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8664897" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/(SICI)1098-1004(1996)7:1&lt;23::AID-HUMU3&gt;3.0.CO;2-Q" target="_blank">Full Text</a>]
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<a id="Young1992" class="mim-anchor"></a>
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Young, E. P.
<strong>Prenatal diagnosis of Hurler disease by analysis of alpha-iduronidase in chorionic villi.</strong>
J. Inherit. Metab. Dis. 15: 224-230, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1527990/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1527990</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1527990" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF01799636" target="_blank">Full Text</a>]
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<a id="Zheng2003" class="mim-anchor"></a>
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Zheng, Y., Rozengurt, N., Ryazantsev, S., Kohn, D. B., Satake, N., Neufeld, E. F.
<strong>Treatment of the mouse model of mucopolysaccharidosis I with retrovirally transduced bone marrow.</strong>
Molec. Genet. Metab. 79: 233-244, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12948739/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12948739</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12948739" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s1096-7192(03)00116-1" target="_blank">Full Text</a>]
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Hilary J. Vernon - updated : 01/13/2022
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Hilary J. Vernon - updated : 07/07/2021<br>Ada Hamosh - updated : 05/29/2018<br>Jane Kelly - updated : 4/18/2016<br>Ada Hamosh - updated : 4/8/2015<br>Cassandra L. Kniffin - updated : 8/16/2010<br>Marla J. F. O'Neill - updated : 10/30/2009<br>Cassandra L. Kniffin - updated : 7/25/2007<br>Marla J. F. O'Neill - updated : 11/10/2006<br>Cassandra L. Kniffin - updated : 8/3/2004<br>Victor A. McKusick - updated : 5/18/2004<br>Victor A. McKusick - updated : 1/5/2004<br>Victor A. McKusick - updated : 10/28/2003<br>Gary A. Bellus - updated : 10/21/2003
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Kelly A. Przylepa : 6/5/2002
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<h3>
<span class="mim-font">
<strong>#</strong> 607014
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HURLER SYNDROME
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<em>Alternative titles; symbols</em>
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MUCOPOLYSACCHARIDOSIS TYPE IH; MPS1-H
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<strong>SNOMEDCT:</strong> 65327002; &nbsp;
<strong>ICD10CM:</strong> E76.01; &nbsp;
<strong>ORPHA:</strong> 579, 93473; &nbsp;
<strong>DO:</strong> 0111390; &nbsp;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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4p16.3
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Mucopolysaccharidosis Ih
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607014
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Autosomal recessive
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3
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IDUA
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252800
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because Hurler syndrome is caused by homozygous or compound heterozygous mutation in the gene encoding alpha-L-iduronidase (IDUA; 252800) on chromosome 4p16.</p>
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<strong>Description</strong>
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<p>The mucopolysaccharidoses are a group of inherited disorders caused by a lack of specific lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs), or mucopolysaccharides. The accumulation of partially degraded GAGs causes interference with cell, tissue, and organ function.</p><p>Deficiency of alpha-L-iduronidase can result in a wide range of phenotypic involvement with 3 major recognized clinical entities: Hurler (MPS IH), Scheie (MPS IS; 607016), and Hurler-Scheie (MPS IH/S; 607015) syndromes. Hurler and Scheie syndromes represent phenotypes at the severe and mild ends of the MPS I clinical spectrum, respectively, and the Hurler-Scheie syndrome is intermediate in phenotypic expression (McKusick, 1972).</p><p>MPS I is more frequent than MPS II (Hunter syndrome; 309900), which has no corneal clouding and pursues a slower course.</p>
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<strong>Nomenclature</strong>
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<p>McKusick et al. (1972) suggested that the Hurler syndrome might be called MPS IH and the Scheie syndrome MPS IS. </p>
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<strong>Clinical Features</strong>
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<p>The clinical features of Hurler syndrome include coarse facies, corneal clouding, mental retardation, hernias, dysostosis multiplex, and hepatosplenomegaly. Children with Hurler syndrome appear normal at birth and develop the characteristic appearance over the first years of life (Wraith et al., 1987). </p><p>Wraith et al. (1987) reviewed 27 Hurler patients, 10 of which were evaluated prior to biochemical diagnosis. Diagnosis was established at a mean age of 21 months (range, 5-63 months). Seventeen of the children (63%) came to clinical attention with hernia prior to the diagnosis of Hurler syndrome. The average age at death was 6.25 years in their series of 27 patients with a range of 1.3 to 10.9 years. </p><p>Cleary and Wraith (1995) described the presenting features of 39 patients with mucopolysaccharidosis type IH. The mean age at diagnosis was approximately 9 months in this study. An earlier age at diagnosis is likely to lead to better results following therapy such as bone marrow transplantation. Clinical features that should arouse suspicion of MPS IH include frequent ear, nose and throat surgery and recurrent hernias. </p><p>McDowell et al. (1993) described a family in which sibs with comparable deficiencies of alpha-L-iduronidase had rather different clinical severity and disease progression. The cases underscored the need for caution in counseling and the limitations of using sibs as controls in evaluating the outcome of treatment. </p><p><strong><em>Head and Neck</em></strong></p><p>
Gorlin et al. (2001) described the facial phenotype. A slight coarsening of the facial features at 3 to 6 months of age is usually the first abnormality detected. The head is large with bulging frontal bones. The skull is often scaphocephalic secondary to premature closure of the metopic and sagittal sutures. The nasal bridge is depressed with broad nasal tip and anteverted nostrils. The cheeks are full. The lips are enlarged and the mouth is usually held open, particularly after age 3 years. Chronic nasal discharge is present.</p><p>Corneal clouding is common. Optic nerve head swelling was observed in 8 of 14 eyes of Hurler syndrome patients reported by Collins et al. (1990). Glaucoma has also been reported to occur in MPS IH (Nowaczyk et al., 1988). Retinal degeneration commonly occurs in MPS I (Caruso et al., 1986). </p><p>Huang et al. (2015) studied the chorioretinopathy in 3 patients with MPS I. The first patient (28 years old) exhibited multifocal depigmented retinopathy in both eyes. The second patient (12 years old) had mild parafoveal retinal folds and mild swollen discs in both eyes. The third patient (33 years old) had a myelinated nerve fiber layer in the right eye. In the first patient, spectral-domain optical coherence tomography (SD-OCT) showed focal choroidal thinning in the depigmented retinopathy areas. In the other 2 patients, SD-OCT showed a fuzzy and thickened external limiting membrane at the fovea. </p><p>The neck is short and there is odontoid hypoplasia. Vertebral subluxation with cord compression can occur (Thomas et al., 1985). </p><p>In a review of cervical spine x-rays in 21 children with mucopolysaccharidosis, Belani et al. (1993) found odontoid hypoplasia in 94%, with 38% demonstrating C1-C2 subluxation. </p><p><strong><em>Cardiovascular Features</em></strong></p><p>
Cardiac disease is common. Acute cardiomyopathy associated with endocardial fibroelastosis has been a presenting condition in some infants with MPS I less than 1 year of age (Donaldson et al., 1989). </p><p>Krovetz et al. (1965) reviewed the cardiovascular findings in 58 autopsy reports. There was valvular involvement in 40 of 58 cases, coronary artery narrowing in 20 of 58 patients, and endocardial fibroelastosis in 11 of 58 patients. They suggested that coronary insufficiency can occur but that Hurler patients are prohibited by their retarded development to communicate this effectively. </p><p>Renteria et al. (1976) described the cardiac disease in 5 necropsy cases of Hurler syndrome. All had narrowing of the extramural coronary arteries, cardiac valve thickening (left-sided greater than right-sided), generalized thickening of mural endocardium, and 'stiffening' of the myocardial walls. </p><p>Wippermann et al. (1995) studied 84 patients with MPS disorders. Echocardiography revealed mitral regurgitation in 10 of 12 MPS IH patients and aortic regurgitation in 4 of 12 MPS IH patients. Aortic and mitral valve thickening was also detected in the patients. </p><p>Braunlin et al. (2019) described cardiac features in 7 infants with MPS IH who had hematopoietic stem cell transplantation (HCT) before 6 months of age. Prior to HCT, 2 patients had mitral regurgitation, 3 had patent foramen ovale, and 1 patient had atrial flutter and severely decreased cardiac function requiring intensive care management. After HCT, 2 patients had mitral regurgitation, 2 had left ventricular hypertrophy, and 3 had patent foramen ovale. One patient died unexpectedly 69 days post-HCT. Overall survival was not increased compared to a cohort of patients who had HCT between 6 and 18 months of age. </p><p><strong><em>Respiratory Features</em></strong></p><p>
Frequent upper and lower respiratory tract infections are common. Respiratory obstruction occurs secondary to enlargement of tonsils and adenoids (Shapiro et al., 1985). </p><p>Narrow tracheas also contribute to upper airway construction. Peters et al. (1985) reported that 9 of 56 patients with MPS disorders had small tracheal diameters on their frontal chest radiographs. Autopsy of an MPS IH patient whose tracheal diameter measured 5 mm revealed that the epiglottis, aryepiglottic folds, and the vocal cords were enlarged and mainstem bronchi were thickened. This resulted primarily from glycosaminoglycan deposition in the connective tissues. </p><p>Semenza and Pyeritz (1988) studied respiratory complications in 4 patients with MPS IH. All had tonsillar and adenoidal hypertrophy, tongue enlargement, and supraglottic narrowing. Two patients studied by polysomnography had obstructive sleep apnea. </p><p>Belani et al. (1993) described the perioperative care in 30 children with MPS disorders, including 21 Hurler or Hurler-Scheie patients. They described anesthetic results in 14 patients with Hunter syndrome. During laryngoscopy, vocal cords were visible in only 19 of 55 anesthetic events. Following extubation, upper airway obstruction was noted 25 times. </p><p><strong><em>Musculoskeletal System</em></strong></p><p>
Length is often normal until about 2 years of age when growth stops; by age 3 years height is less than the third percentile (Gorlin et al., 2001).</p><p>In infancy, bone trabeculation is coarse. In late infancy and childhood, a pattern of skeletal changes called 'dysostosis multiplex' develops (McKusick, 1972). The skull is large with narrow orbits. The calvaria is thickened and the sagittal and lambdoidal sutures close prematurely. The sella becomes J-shaped. The ribs have been described as oar-shaped with narrowing at the vertebral ends and broadening at the sternal ends. Clavicles are short, thick, and irregular. The vertebral bodies are dysplastic with biconcave endplates and hook-shaped configuration of the lower thoracic and upper lumbar vertebral bodies. The pelvis is poorly formed with small femoral heads and coxa valga. Iliac wings are flared. The long tubular bones show diaphyseal widening with small, deformed epiphyses. Phalanges are bullet-shaped with proximal pointing of the second to fifth metacarpals.</p><p>Neuhauser et al. (1968) concluded that subarachnoid cysts are often responsible for the enlarged sella in Hurler syndrome. </p><p>Joint stiffness is a common feature of all the MPS disorders with the exception of Morquio syndrome (253000; 253010). The joint function abnormalities probably result from a combination of the metaphyseal deformities and thickened joint capsules secondary to glycosaminoglycan deposition and fibrosis (Neufeld and Muenzer, 2001).</p><p>Progressive lumbar gibbus or kyphosis is commonly seen in the MPS disorders (Neufeld and Muenzer, 2001). Tandon et al. (1996) described the spinal problems and their management in 12 patients with Hurler syndrome who were followed up for a mean of 4.5 years following bone marrow transplantation. High lumbar kyphosis was seen in 10 patients and was associated with thoracic scoliosis in 1. Isolated thoracic scoliosis was seen in another. One patient had no significant problems in the thoracic or lumbar spine but had odontoid hypoplasia, which was also seen in 3 other children. Four of the 8 patients in whom MRI of the cervical spine had been performed had abnormal soft tissue around the tip of the odontoid. Neurologic problems were seen in 2 patients. </p><p>Carpal tunnel syndrome, a common complication in the mucopolysaccharidoses, probably results from a combination of excessive lysosomal storage in the connective tissue of the flexor retinaculum and a deformity secondary to the underlying skeletal dysplasia. Wraith and Alani (1990) performed nerve conduction studies on 18 patients with various forms of mucopolysaccharidoses and mucolipidosis III. All patients studied, with the exception of patients younger than 2 years, had evidence of thenar muscle wasting and a typical 'claw-hand' deformity. All 3 patients with MPS IH were found to have carpal tunnel syndrome. Two of the 3 received bone marrow transplantation at 14 months and 2.3 years, respectively. Neither showed improvement following transplantation. </p><p><strong><em>Nervous System</em></strong></p><p>
Developmental delay is often apparent by 12 to 24 months of age, with a maximum functional age of 2 to 4 years followed by progressive deterioration. Most children develop limited language because of developmental delay, chronic hearing loss, and enlarged tongue (Neufeld and Muenzer, 2001).</p><p>In a study of 27 patients with MPS IH, Wraith et al. (1987) found that all had head circumferences at or above the 95th percentile. Only 5 children developed signs and symptoms of raised intracranial pressure which required shunt. </p><p>Lee et al. (1993) characterized cranial MRI findings in 6 children with Hurler syndrome. All exhibited cribriform or cystic changes: low signal intensity with respect to white matter on T1-weighted images and high-signal intensity on the T2-weighted images. The changes corresponded pathologically to perivascular accumulations of glycosaminoglycan within the foam cells in the Virchow-Robin spaces (Norman et al., 1959). Myelination delay, atrophy, and ventricular enlargement were also found in their patients. </p><p><strong><em>Dermatologic Features</em></strong></p><p>
Hanson et al. (2003) described 2 infants with extensive dermal melanocytosis in association with GM1-gangliosidosis type I (230500) and Hurler syndrome, respectively. Clinically, dermal melanocytosis associated with lysosomal storage disease is characterized by extensive, blue cutaneous pigmentation with dorsal and ventral distribution, indistinct borders, and persistent and/or 'progressive' behavior. A literature analysis revealed 37 additional cases. The most common lysosomal storage disease associated with dermal melanocytosis was Hurler syndrome (24 of 39 cases), followed by GM1-gangliosidosis (11 of 39 cases). Hanson et al. (2003) concluded that in the appropriate clinical setting, an unusual presentation of dermal melanocytosis in an infant may be a cutaneous sign of an underlying lysosomal storage disease. </p>
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</div>
<div>
<h4>
<span class="mim-font">
<strong>Biochemical Features</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>The enzyme deficient in Hurler syndrome is alpha-L-iduronidase (252800).</p><p>Danes and Bearn (1965) found that cellular accumulation of mucopolysaccharides persists in cultured fibroblasts. Fratantoni et al. (1968) showed that the accumulation results from inefficient degradation of intracellular mucopolysaccharide rather than excessive synthesis or reduced secretion. Furthermore, they found that mixing of fibroblasts from Hurler and Hunter patients causes mutual correction of the intracellular accumulation of mucopolysaccharides. Medium in which cells of the other type or normal cells had been incubated was also effective in correcting the defect. Thus, isolation and identification of the corrective factor in the medium opened up possibilities of clarifying the normal mechanisms of MPS degradation, as well as therapy. Differentiation of the Sanfilippo syndrome (MPS III; see 252900) from the Hurler and Hunter syndromes was also possible by this mixed culture method. </p><p>Wiesmann and Neufeld (1970) found no cross-correction of Scheie and Hurler fibroblasts with those from Sanfilippo and Hunter patients. Both disorders showed deficiencies of alpha-L-iduronidase. </p><p>Schuchman and Desnick (1988) reported the presence of cross-reactive immunologic material (CRIM) in individuals from each of the 3 MPS I subtypes. Furthermore, they identified effector compounds that enhanced the residual activities in subtype extracts into the heterozygote range. The polyclonal antibody with which this work was done, however, is under suspicion because of the findings of Scott et al. (1990) that it gave a fallacious result when used for the mapping of the IDUA gene in somatic cell hybrids. </p><p>Brooks et al. (1992) found that a clinically typical patient with Hurler syndrome, the source of cell line GM2827, had, despite severe deficiency of enzyme, an activity level of alpha-L-iduronidase protein at least 6 times greater than the mean level found in normal control fibroblasts. This was the only 1 of 23 patients who had protein levels greater than 7% of the mean level detected in normal controls. </p>
</span>
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<h4>
<span class="mim-font">
<strong>Diagnosis</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p><strong><em>Biochemical Diagnosis</em></strong></p><p>
The earliest diagnostic tests for the MPS disorders were based on the urinary excretion of glycosaminoglycans. Pennock (1976) noted several methods that had been developed from semiquantitative spot tests to more precise qualitative and quantitative assays. </p><p>Spot tests are quick and inexpensive but are subject to both false-positive and false-negative results. De Jong et al. (1991) checked the reliability of the Ames MPS paper spot test, which is based on the Azure A dye. They sent a series of urine samples to 3 laboratories where the spot test is part of the metabolic screening for mucopolysaccharidoses. In these laboratories, false-negative results ranged between 19% and 35% and false-positive results ranged between 12 and 29% of all samples submitted. In contrast, the quantitative dimethylmethylene blue test detected an increased glycosaminoglycan content in all urine samples from mucopolysaccharidosis patients and gave no false-positive results. </p><p>Definitive diagnosis is established by alpha-L-iduronidase enzyme assay using artificial substrates (fluorogenic or chromogenic) in cultured fibroblasts or isolated leukocytes (Hall et al., 1978). </p><p>Carrier testing can be performed by differentiating normal enzyme activity from half-normal levels of enzyme activity. Wappner and Brandt (1976) studied alpha-L-iduronidase activity in mixed leukocyte preparations in 10 families in which the Hurler syndrome had occurred. Affected patients, heterozygotes, and normal subjects were clearly distinguished by alpha-L-iduronidase activity alone. Patients had 0 to 3%, obligate heterozygotes 19 to 60%, and normal subjects 83 to 121% of the mean normal activity. There was no overlap between heterozygotes and normal subjects. </p><p>Low activity 'pseudodeficiency' alleles exist, however, and complicate biochemical carrier testing. Taylor and Thomas (1993) reported apparent deficiency of alpha-iduronidase in a clinically normal individual. The same finding was made in leukocytes and skin fibroblasts which functioned normally in correction assays in mixed culture. Previously reported instances of pseudodeficiency involved individuals who were obligate heterozygotes for Hurler syndrome, having 1 Hurler allele and presumably 1 pseudodeficiency allele (Gatti et al., 1985; Whitley et al., 1987). Whitley et al. (1987) described a low activity 'pseudodeficiency' allele at the alpha-L-iduronidase locus. It was found in a phenotypically normal obligate heterozygote with exceedingly low levels of enzyme activity. The presence of this allele can complicate carrier detection and prenatal diagnosis. </p><p><strong><em>Prenatal Diagnosis</em></strong></p><p>
Prenatal diagnosis is possible on both cultured amniotic fluid cells and chorionic villus biopsies. Young (1992) stressed the importance of obtaining an adequate chorionic villi tissue sample. Twenty-four pregnancies at risk for Hurler disease were monitored by measurement of alpha-iduronidase in chorionic villi. Adequate samples were obtained for direct assay of the villi in 22 pregnancies. Pregnancies were terminated in 5 samples found to be affected. In another pregnancy, an equivocal result was obtained on direct assay, but analysis of the cultured chorionic cells showed the fetus to be affected. In 1 pregnancy in which a very small sample was obtained, direct assay indicated the fetus to be unaffected. However, amniocentesis revealed an affected pregnancy. </p><p><strong><em>Molecular Diagnosis</em></strong></p><p>
Molecular diagnosis of Hurler syndrome is difficult because of the genetic heterogeneity in MPS I. Using a combination of mutation analysis and mutation scanning in a study of 85 MPS I families (73 Hurler, 5 Hurler/Scheie, 7 Scheie), Beesley et al. (2001) identified both IDUA mutations in 81 (95%) families, one IDUA mutation in 3 (3.5%) families, and none in 1 (1.1%) family. The families were screened for 9 known mutations. W402X (252800.0001) was the most frequent mutation in their population (45.3%), followed by Q70X (252800.0002) (15.9%). In 30 families, one or both of the mutations were not identified, which accounted for 25.9% of the total alleles. Therefore, all 14 exons of the IDUA gene were screened in these patients and 23 different sequence changes were found, 17 of which were previously unknown. </p>
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<div>
<h4>
<span class="mim-font">
<strong>Clinical Management</strong>
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</h4>
</div>
<span class="mim-text-font">
<p>Wang et al. (2011) described the ACMG standards and guidelines for the diagnostic confirmation and management of presymptomatic individuals with lysosomal storage diseases. </p><p><strong><em>Anesthesia</em></strong></p><p>
Belani et al. (1993) described the perioperative care, morbidity, and mortality in 30 patients with mucopolysaccharidosis, including 21 patients with Hurler or Hurler-Scheie syndrome. During 141 anesthetic administrations, 2 children with Hurler syndrome died intraoperatively. The first death occurred in a boy, aged 3 years 9 months, who demonstrated a sudden elevation of ST-T segments on ECG, then rapid bradycardia and death. At autopsy, both his coronary vessels were occluded. The other death occurred in a 14-month-old child who had normal preoperative ECG and cardiac echocardiogram. During cardiac catheterization, he developed ventricular tachycardia and subsequent cardiac arrest. At autopsy, there was marked concentric intimal and subintimal fibrosis of both coronary arteries, which was not substantiated on the coronary angiogram. </p><p><strong><em>Plasma Infusion/Fibroblast Transplantation</em></strong></p><p>
Improvement, clinical and chemical, with plasma infusions was claimed by Di Ferrante et al. (1971), but further trials were disappointing. Gibbs et al. (1983) did not find fibroblast transplantation to be therapeutically useful in either Hurler syndrome or Sanfilippo syndrome. </p><p><strong><em>Bone Marrow Transplantation (BMT)</em></strong></p><p>
Hugh-Jones (1983) pointed out the importance of early diagnosis of mucopolysaccharidoses because of the effectiveness of bone marrow transplantation. He reported that hernia was a feature in 13 of 15 cases of MPS I and in 7 of 9 cases of MPS II, and suggested that hernia before the age of 6 months may be a valuable diagnostic clue. </p><p>Hopwood et al. (1993) described the outcome of bone marrow transplantation in 2 patients who were subsequently found to be homozygous for the relatively common W402X mutation (252800.0001). They received BMT at the ages of 14 and 11 months and were 12% and 14 years old, respectively, at the time of report. Untreated patients homozygous for this mutation have a very severe clinical phenotype with rapid clinical deterioration and death before 6 years of age. The 12-year-old patient showed limited mobility but was coping well at school; the other patient was wheelchair-bound with severe disability in his lower limbs and attended a school for the physically handicapped. Both patients had less than normal intelligence with slowly continuing losses. </p><p>The Storage Disease Collaborative Study Group (Peters et al., 1998) reported their findings on 54 patients with MPS I. The patients received high-dose chemotherapy with or without irradiation and BMT from HLA-genotypically identical sib (GIS) or HLA-haploidentical-related (HIR) donors between 1983 and 1995. Thirty-nine of 54 patients (72%) were engrafted following the first BMT. The probability of grade II to IV acute graft-vs-host disease (GVHD; see 614395) at 100 days was 32% for GIS and 55% for HIR patients. The actuarial probability of survival at 5 years was 64% for all patients, 75% for GIS patients, 53% for HIR patients, and 53% for patients with donor marrow engraftment. The baseline Mental Developmental Index (MDI) was examined both for children less than and greater than 24 months of age at BMT. Children who received a transplant before 24 months had a mean baseline MDI of 78, whereas those who received a transplant after 24 months of age had a mean baseline MDI of 63 (P = 0.0002). Both baseline and post-BMT neuropsychologic data were available for 26 of 30 engrafted survivors. Of 14 patients who received a transplant before 24 months of age, 9 demonstrated developmental trajectories that were normal or somewhat slower than normal. In contrast, of 12 patients who received a transplant after 24 months of age, only 3 showed developmental trajectories that were normal or somewhat slower than normal (P = 0.01). Children were more likely to maintain normal cognitive development if they were fully engrafted following BMT from a donor with homozygous normal leukocyte alpha-L-iduronidase enzyme activity. </p><p><strong><em>Enzyme Replacement</em></strong></p><p>
Kakkis et al. (2001) treated 10 patients with MPS I (aged 5 to 22 years) with recombinant human alpha-L-iduronidase at a dose of 125,000 U per kg of body weight given intravenously once weekly for 52 weeks. Hepatosplenomegaly decreased significantly in all patients, and the size of the liver was normal for body weight and age in 8 patients by 26 weeks. The rate of growth in height and weight increased by a mean of 85%% and 131%, respectively, at 52 weeks in the 6 prepubertal patients. The mean maximum range of motion of shoulder flexion and elbow extension increased significantly. The number of episodes of apnea and hypopnea during sleep decreased by 61%. New York Heart Association functional class improved by 1 or 2 classes in all patients. Urinary glycosaminoglycan excretion decreased after 3 to 4 weeks of treatment; the mean reduction at 52 weeks was 63% of baseline values. Five patients had transient urticaria during infusions. Serum antibodies to alpha-L-iduronidase were detected in 4 patients. </p><p>Wang et al. (2009) reported a girl with severe MPS I who began enzyme replacement therapy (ERT) at age 15 months and underwent hematopoietic stem cell transplantation at age 20 months. At that time, she had begun to walk and spoke a few words. She had complete engraftment with normalization of plasma IDUA activity. At age 4 years, she was slightly developmentally delayed with mild to moderate sensorineural hearing loss, but was making progress. Brain imaging studies showed improvement of white matter abnormalities and ventricular dilatation following ERT even before stem cell transplant, with continued improvement in brain imaging abnormalities until the time of the report. The findings suggested that ERT may improve brain MRI abnormalities in patients with MPS, even though ERT had previously been thought not to cross into the brain. Wang et al. (2009) offered some explanations, including lessening of somatic GAG accumulation, repair of damaged brain endothelium, and possibly small amounts of enzyme being able to permeate the brain. </p><p><strong><em>Gene Therapy</em></strong></p><p>
Because allogeneic bone marrow transplantation is not available to all patients, Fairbairn et al. (1996) considered an alternative approach based on transfer and expression of the normal gene in autologous bone marrow. They constructed a retroviral vector carrying the full-length cDNA for alpha-L-iduronidase and used it to transduce bone marrow from patients with this disorder. They demonstrated successful gene transfer into primitive CD34+ cells and subsequent enzyme expression in their maturing progeny. The efficiency of gene transfer as assessed by PCR analysis of hematopoietic colonies was 25 to 56%. The enzyme was secreted into the medium and functional localization was demonstrated by reversal of the phenotypic effects of lysosomal storage in macrophages. Fairbairn et al. (1996) concluded that retroviral gene transfer into human bone marrow may offer effective gene therapy of Hurler syndrome in young patients without a matched sib donor. </p><p>Keeling et al. (2001) found that a Hurler syndrome fibroblast cell line heterozygous for the IDUA stop mutations Q70X and W402X showed a significant increase in alpha-L-iduronidase activity when cultured in the presence of gentamicin, resulting in the restoration of 2.8% of normal alpha-L-iduronidase activity. Gentamicin treatment reduced glycosaminoglycan accumulation in Hurler cells to a normal level for at least 2 days after gentamicin treatment was discontinued. The reduction in the GAG level was also reflected in a marked reduction in lysosomal vacuolation, as shown by fluorescence microscopy. The authors suggested that partial suppression of premature stop mutations by gentamicin may provide an effective treatment for Hurler syndrome patients with these mutations in the IDUA gene. </p><p>Di Natale et al. (2002) used a late-generation lentiviral vector to evaluate the usefulness of this vector system for the transfer and expression of the human IDUA cDNA in MPS I fibroblasts. They observed that the level found in normal cells and expression persisted for at least 2 months. In addition, transduced MPS I fibroblasts were capable of clearing intracellular radiolabeled glycosaminoglycan. Pulse-chase experiments on transduced fibroblasts showed that the recombinant enzyme was synthesized as a 76-kD precursor form and processed to a mature form; it was released from transduced cells and was endocytosed into a second population of untreated MPS I fibroblasts via a mannose 6-phosphate receptor. </p><p>Allogeneic bone marrow transplantation before the age of 2 years halts disease progression in Hurler syndrome and prolongs life, but many children lack a bone marrow donor. Staba et al. (2004) investigated the feasibility of using cord blood transplants from unrelated donors and a myeloablative preparative regimen that did not involve total-body irradiation in young children with Hurler syndrome. Over a 7-year period, they gave 20 consecutive children with Hurler syndrome busulfan, cyclophosphamide, and antithymocyte globulin in preparation for receiving cord blood transplants from unrelated donors. Cord blood donors were discordant for up to 3 of 6 HLA markers. Neutrophil engraftment occurred a median of 24 days after transplantation. Grade II or grade III acute graft-versus-host disease occurred in 5 patients; none had extensive chronic graft-versus-host disease. Seventeen of the 20 children were alive a median of 905 days after transplantation, with complete donor chimerism and normal peripheral blood alpha-L-iduronidase activity. Transplantation improved neurocognitive performance and decreased somatic features of Hurler syndrome. </p><p>Gentner et al. (2021) reported interim results of a phase 1-2 clinical trial in 8 children with Hurler syndrome to evaluate safety effectiveness of treatment with autologous hematopoietic stem and progenitor cells transduced ex vivo with an alpha-L-iduronidase-encoding lentiviral vector. The average age of the patients when treated with the gene therapy was 1.9 years, and the median follow-up was 2.1 years. The safety profile was similar to that of autologous hematopoietic stem cell transplantation. All 8 patients demonstrated sustained engraftment of gene-corrected cells and had supraphysiologic blood IUDA enzyme activity within 1 month of treatment. Patients demonstrated progressive gain of language and cognitive skills, continued motor development, improved or stable findings on brain and spine MRI, reduced joint stiffness, and normal growth. Urinary glycosaminoglycans reached normal levels at 12 months in 4 of 5 patients tested. CSF IUDA activity also increased and CSF glycosaminoglycan levels decreased. Kharbanda and Dvorak (2021) concluded that the gene therapy trial by Gentner et al. (2021) represented a step closer to a therapy that would result in complete correction of Hurler syndrome. </p><p><strong><em>Umbilical Cord Blood Transplantation</em></strong></p><p>
Poe et al. (2014) reported 31 patients with Hurler syndrome who underwent umbilical cord blood transplantation between June 1997 and February 2013 and were evaluated at baseline and every 6 to 12 months thereafter. All 31 patients underwent complete neurodevelopmental evaluation (median follow-up 7.3 years, range 2-21.7) and a median of 7.0 evaluations (range 3-18 ). Younger age at transplantation was associated with improved cognitive function (p = 0.001), receptive and expressive language (p = 0.004 and p = 0.01), and adaptive behavior (p = 0.03). Early age at transplantation was a strong predictor of cognitive, language, and adaptive behavior outcomes. Children younger than 9 months at the time of transplant showed normal cognitive development. </p>
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<div>
<h4>
<span class="mim-font">
<strong>Inheritance</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Hurler syndrome is an autosomal recessive disorder (Bunge et al., 1995; Yamagishi et al., 1996). </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Bunge et al. (1995) identified 13 novel and 7 previously reported mutations of the IDUA gene, covering 88% of mutant alleles and 86% of genotypes, in a total of 29 patients with MPS I, including 5 with Hurler syndrome. </p>
</span>
<div>
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</div>
<div>
<h4>
<span class="mim-font">
<strong>Population Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>If the mutation rates are the same and the heterozygotes for the Hurler and Hunter syndromes have no reproductive advantage or disadvantage, the Hunter syndrome should be 1.5 times more frequent among newborns than the Hurler syndrome (McKusick, 1970). Lowry and Renwick (1971) gave estimates of the frequency of the Hurler syndrome and the Hunter syndrome in the province of British Columbia. Lowry et al. (1990) stated that no case of the Hurler syndrome had been encountered since 1981 and no case of the Hunter syndrome since 1971. The frequency of the Hunter syndrome between 1952 and 1986 was estimated to be 1 in 110,950 live male births; the frequency of the Hurler syndrome was estimated to be 1 in 144,274 live births. Over a period of years during which he was responsible for identification of essentially all cases of mucopolysaccharidosis in Israel, Bach (1990) found no cases of Hurler syndrome in Ashkenazim. Hurler syndrome in Ashkenazi Jews appears to be rare in the experience of others; thus, this gene may be similar to the PKU gene, which is rare in this group. </p><p>Using multiple ascertainment sources, Nelson et al. (2003) obtained an incidence rate of MPS IH in western Australia for the period 1969 to 1996 of approximately 1 in 107,000. </p><p>By analyzing allele and haplotype frequencies for 2 polymorphisms within the IDUA gene in the normal population and in MPS IH patients, Scott et al. (1992) found linkage disequilibrium. One VNTR allele was present in 57% of MPS I patients as compared with 37% in the normal population. They interpreted this as indicating the presence of a major MPS I allele. </p><p>Relevant to the question of the relative frequency and birth prevalence of Hurler syndrome and Hunter syndrome is the report by Poorthuis et al. (1999) on the frequency of lysosomal storage diseases in the Netherlands. MPS I had the highest calculated birth prevalence of 1.19 per 100,000 (25% of all cases of MPS diagnosed); the birth prevalence of MPS II was 0.67 per 100,000 (1.30 per 100,000 male live births). (The second most frequent mucopolysaccharidosis was MPS IIIA (Sanfilippo syndrome type A; 252900) with an estimated birth prevalence of 1.16 per 100,000.) </p><p>In a group of 46 European patients with MPS I, Bunge et al. (1994) found that the 2 common nonsense mutations, W402X (252800.0001) and Q70X (252800.0002), were identified in 37% and 35% of mutant alleles, respectively. Considerable differences were seen in the frequency of these 2 mutations in patients from Norway and Finland as compared with other European countries, mainly the Netherlands and Germany. In Scandinavia, W402X and Q70X accounted for 17% and 62% of the MPS I alleles, respectively, while in other European countries W402X was about 2.5 times more frequent (48%) than Q70X (19%). Bunge et al. (1994) also described 8 novel mutations, including 4 missense mutations, 1 nonsense mutation, 1 insertion of 2 basepairs, and 2 deletions of 1 and 12 basepairs. All the patients in this study had a typical, severe form of the disease, MPS IH, with marked skeletal changes, hepatosplenomegaly, and mental retardation. </p><p>Yamagishi et al. (1996) defined the IDUA mutations in 19 Japanese MPS I patients, including 2 pairs of sibs, with various clinical phenotypes; Hurler syndrome, 6 cases; Hurler/Scheie syndrome, 7 cases; Scheie syndrome, 6 cases. Two common mutations accounted for 42% of the 38 alleles in these patients. One was a novel 5-bp insertion between the T at nucleotide 704 and the C at nucleotide 705 (704ins5; 252800.0014), which was seen only in the Japanese population. The other was a missense mutation, R89Q (252800.0015), which is seen also in Caucasians, although uncommonly. No Japanese patient was found to carry the W402X or Q70X alleles, the 2 most common MPS I mutations in Caucasians. Homozygosity for the 704ins5 mutation was associated with a severe phenotype; homozygosity for the R89Q mutation was associated with a mild phenotype. Compound heterozygosity for these 2 mutations produced an intermediate phenotype. Haplotype analysis using polymorphisms linked to IDUA locus demonstrated that each of these 2 common mutations occurred on a different specific haplotype, suggesting that individuals with each of these common mutations derived from a common founder. The mild-intermediate-severe phenotypic relationships of the 2 common Japanese mutations fulfill the prediction of McKusick et al. (1972). </p><p>Scott et al. (1995) indicated that a total of 46 mutations in the IDUA gene had been defined: 8 nonsense mutations, 21 missense mutations, 3 splice site mutations, and 14 minor deletions and/or insertions. Furthermore, 30 polymorphisms or nonpathogenic sequence variants had been defined, including 7 amino acid substitutions. Among patients of European origin, there were 2 major mutations associated with MPS I: W402X and Q70X, which together accounted for between 24% (Italian) and 84% (Scandinavian) of the MPS I alleles in patients of European origin. Different alleles predominate in Japanese patients. </p><p>Gatti et al. (1997) screened for IDUA mutations in 27 Italian patients with MPS I. Mutations were found in 18 patients, with 28 alleles identified. The 2 most common mutations in northern Europeans, W402X and Q70X, accounted for 11 and 13% of the alleles, respectively. The P533R (252800.0003) mutation accounted for 11% of the 54 alleles and seemed to be confined to Sicily; the frequency of P533R was 3% in a British/Australian study. Two P533R homozygotes were stated to have an intermediate phenotype in one and a mild phenotype in a second. </p><p>Lin et al. (2009) analyzed the incidence of MPS in Taiwan between 1984 and 2004 and found that the combined birth incidence for all MPS cases was 2.04 per 100,000 live births. MPS II (Hunter syndrome) had the highest calculated birth incidence (1.07 per 100,000 live births), comprising 52% of all MPS cases diagnosed. The birth incidences of MPS I, III (Sanfilippo syndrome), IV (Morquio syndrome), and VI (Maroteaux-Lamy syndrome) were 0.11, 0.39, 0.33, and 0.14 per 100,000 live births, respectively, and accounted for 6%, 19%, 16%, and 7% of all MPS, respectively. Although the overall incidence of MPS in Taiwan was consistent with reports from Western populations, Lin et al. (2009) noted that in contrast to reports of a higher incidence of MPS I in most Western populations, their study showed a higher incidence of MPS II in Taiwan. </p><p>Vazna et al. (2009) reported that 21 Czech and Slovak patients had been diagnosed with MPS I over the past 30 years, 16 with a severe clinical presentation (Hurler syndrome), 2 less severe (Scheie syndrome), and 3 of intermediate severity (Hurler-Scheie syndrome). Mutation analysis in 22 patients showed a high prevalence of the null mutations W402X and Q70X (12 and 7 alleles, respectively). The authors stated that missense mutations located predominantly in the hydrophobic core of the enzyme were associated with the severe phenotype, whereas missense mutations localized to the surface of the enzyme were usually associated with the attenuated phenotypes. Mutations in the 130 C-terminal amino acids led to clinical manifestations, indicating functional importance of the C terminus of the IDUA protein. </p><p>Khan et al. (2017) analyzed the epidemiology of the mucopolysaccharidoses in Japan and Switzerland and compared them to similar data from other countries. Data for Japan was collected between 1982 and 2009, and 467 cases with MPS were identified. The combined birth prevalence was 1.53 per 100,000 live births. The highest birth prevalence was 0.84 for MPS II (309900), accounting for 55% of all MPS. MPS I, III (see 252900), and IV (see 253000) accounted for 15%, 16%, and 10%, respectively. MPS VI (253200) and VII (253220) were more rare and accounted for 1.7% and 1.3%, respectively. A retrospective epidemiologic data collection was performed in Switzerland between 1975 and 2008 (34 years), and 41 living MPS patients were identified. The combined birth prevalence was 1.56 per 100,000 live births. The highest birth prevalence was 0.46 for MPS II, accounting for 29% of all MPS. MPS I, III, and IV accounted for 12%, 24%, and 24%, respectively. As seen in the Japanese population, MPS VI and VII were more rare and accounted for 7.3% and 2.4%, respectively. The high birth prevalence of MPS II in Japan was comparable to that seen in other East Asian countries where this MPS accounted for approximately 50% of all forms of MPS. Birth prevalence was also similar in some European countries (Germany, Northern Ireland, Portugal and the Netherlands) although the prevalence of other forms of MPS was also reported to be higher in these countries. </p><p>Matte et al. (2000) analyzed 24 Brazilian MPS I patients for 10 known mutations in the IDUA gene. Only 37% of genotypes and 54% of the alleles were defined using this method, demonstrating a low frequency of these 10 mutations in this population. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Animal Model</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Haskins et al. (1979) described a model of MPS I in the cat, and Shull et al. (1982) and Spellacy et al. (1983) described a model in the dog. </p><p>Shull et al. (1994) reported results of enzyme replacement in the canine model. Recombinant human alpha-L-iduronidase, purified to apparent homogeneity from secretions of a stably transfected Chinese hamster ovary cell line, was administered intravenously to homozygous affected animals in doses of approximately 1 mg. The enzyme rapidly disappeared from the circulation in a biphasic manner, with a half-life of 0.9 and 19 min, respectively, and was taken up primarily by the liver. Biopsy of the liver before and after a trial of 7 doses administered over 12 days showed remarkable resolution of lysosomal storage in both hepatocytes and Kupffer cells. After weekly administration of enzyme to 3 affected animals over a period of 3 months, the level of enzyme was about normal in liver and spleen, lower but significant in kidney and lung, and barely detectable (0-5% of normal) in brain, heart valve, myocardium, cartilage, and cornea. Light and electron microscopic examination showed normalization of lysosomal storage in liver, spleen, and kidney glomeruli, but there was no improvement in brain, heart valves, or cornea. The treated dogs developed complement-activating antibodies against the enzyme but clinical symptoms could be avoided by slow infusion of enzyme and premedication with antihistamine and sedative. </p><p>Grosson et al. (1994) mapped the homologous locus in the mouse, Idua, to chromosome 5 in a continuous linkage group that included the homolog of the Huntington disease gene. Clarke et al. (1997) created a mouse strain completely deficient in iduronidase by targeted disruption of the Idua gene. Russell et al. (1998) reported on the long-term clinical, biochemical, and pathologic course of MPS I in mice, with emphasis on the skeletal and CNS manifestations. Affected mice showed a progressive clinical course with the development of coarse features, altered growth characteristics, and a shortened life span. Progressive lysosomal accumulation was seen in all tissues. Skeletal manifestations represented the earliest clinical findings, with histologic analysis of growth plate and cortical bone revealing evidence of significant early pathology. Analysis of the CNS showed progressive neuronal loss within the cerebellum. In addition, brain tissue from MPS I mice showed increased levels of GM2 and GM3 gangliosides. </p><p>Ohmi et al. (2003) studied the brain of mouse models of MPS I and MPS IIIB (252920) in connection with previous evidence of microglial involvement in the pathogenesis of mucopolysaccharidoses. The studies showed an inflammatory component of brain disease in both of these forms of MPS. </p><p>Immune responses can interfere with the effective use of enzyme replacement in treatment of Hurler syndrome and other genetic deficiencies. To address this problem, Kakkis et al. (2004) studied methods of immune tolerance used in canine organ transplantation research, extending it to the use of soluble proteins in therapeutics. They developed a tolerization regimen for use in a canine model of MPS I. The tolerizing regimen consisted of a limited 60-day course of cyclosporin A and azathioprine combined with weekly intravenous infusions of low-dose recombinant human alpha-L-iduronidase. The experimental dogs tolerized with this regimen maintained a reduced immune response for up to 6 months despite weekly therapeutic doses of enzyme in the absence of immunosuppressive drugs. Successful tolerization depended on high plasma levels of cyclosporin A combined with azathioprine. In addition, the induction of tolerance may require mannose 6-phosphate receptor-mediated uptake because alpha-L-iduronidase and alpha-glucosidase (606800) induced tolerance with the drug regimen whereas ovalbumin and dephosphorylated alpha-L-iduronidase did not. Kakkis et al. (2004) suggested that this approach should be applicable to the treatment of other lysosomal storage disorders and that the strategy might be used for reduction in antibodies associated with autoimmune disease. </p><p>Zheng et al. (2003) transduced bone marrow from Idua knockout male mice with human IDUA cDNA in an MND vector and transplanted it into 6-to-8-week-old, lethally irradiated female Idua -/- mice. Sham-treated mice received Idua -/- bone marrow that was either unmodified or transduced with enhanced GFP. Transplantation of unmodified wildtype bone marrow was effective in reducing storage in liver and spleen but not in kidney or brain. The level of alpha-L-iduronidase activity achieved by transplantation of IDUA-transduced bone marrow varied greatly between experiments. Even modest activity resulted in correction of pathology of kidney, bladder epithelium, fibrocartilage, choroid plexus, and thalamus, as seen by light microscopy; electron microscopy showed the presence of some normal neurons in the cortex. The partial correction of brain pathology was attributed to migration of donor hematopoietic cells, demonstrated by the presence of the Y chromosome and of normal microglia in the brain of mice receiving IDUA cDNA. </p><p>Desmaris et al. (2004) used adenoviral vectors (AAV2 and AAV5) to inject human IDUA into the right putamen in a mouse model of MPS I. After a single injection, enzyme activity was detected throughout the brain, including the contralateral hemisphere, the cerebellum, and the brainstem. In the treated mouse brains, neuropathologic examination showed decreased ganglioside accumulation as well as evidence suggesting reversal of disease pathology in some areas. </p><p>Ciron et al. (2006) reported stereotactic adenoviral-mediated injection of human IDUA into the brains of dogs with MPS1. The dogs were treated between 3 and 4.8 months of age after symptoms had developed. Neuropathologic analysis showed broad and efficient IDUA delivery in the brain, reduced pathology, and improvement of biochemical disease markers in most areas. Clinical improvement could not be assessed. Dogs receiving partial immunosuppression treatment developed a subacute encephalitis with neuroinflammation in the brain. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>History</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>In discussing Otto Ullrich, Wiedemann (1991) gave an extensive account of Ullrich's teacher, Meinhard von Pfaundler, professor of pediatrics at Munich, whose name is often combined with that of Gertrud Hurler. Hurler was a pediatrician who worked for many years in Munich. Wiedemann (1991) commented that 'Anglo-American influence may even cause our young West-German physicians to mispronounce it as if it were spelled 'Hoerler'' (i.e., with an o umlaut rather than a u). </p><p>Bernal and Briceno (2006) examined pottery artifacts from the Tumaco-La Tolita culture, which existed on the border of present-day Colombia and Ecuador approximately 2,500 years ago, and described 3 figurines showing coarse facies, prominent eyebrows, wide mouth, and umbilical hernia, resembling mucopolysaccharidosis IH. Bernal and Briceno (2006) believed these artifacts to be among the earliest artistic representations of disease. </p><p><strong><em>Unclassified Mucopolysaccharidosis</em></strong></p><p>
Brown and Kuwabara (1970) observed 2 sisters, aged 5 and 13 years, with Hurler-like facies, swollen fingers, dwarfed stature, severe progressive joint destruction and peculiar progressive peripheral annular corneal opacification. The parents were Puerto Rican first cousins. Fibroblasts showed metachromasia and increased mucopolysaccharide. Urinary mucopolysaccharide was normal. High doses of vitamins seemed to be beneficial. </p><p>Scott et al. (1973) described a male child who had mucopolysacchariduria, mental retardation, 'dysostosis multiplex' and appearance similar to that of a mucopolysaccharidosis. Death occurred at 47 months from pneumonia. The reticuloendothelial system remained free of mucopolysaccharide although accumulations were found in the perichondrium, coronary arteries, aorta, and glomerular epithelial cells of the kidney. Lipid accumulated in peripheral neurons but not in central neurons. </p>
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>See Also:</strong>
</span>
</h4>
<span class="mim-text-font">
Bach et al. (1993); Menon et al. (1992); Scott et al. (1993)
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
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Hilary J. Vernon - updated : 01/13/2022<br>Hilary J. Vernon - updated : 07/07/2021<br>Ada Hamosh - updated : 05/29/2018<br>Jane Kelly - updated : 4/18/2016<br>Ada Hamosh - updated : 4/8/2015<br>Cassandra L. Kniffin - updated : 8/16/2010<br>Marla J. F. O&#x27;Neill - updated : 10/30/2009<br>Cassandra L. Kniffin - updated : 7/25/2007<br>Marla J. F. O&#x27;Neill - updated : 11/10/2006<br>Cassandra L. Kniffin - updated : 8/3/2004<br>Victor A. McKusick - updated : 5/18/2004<br>Victor A. McKusick - updated : 1/5/2004<br>Victor A. McKusick - updated : 10/28/2003<br>Gary A. Bellus - updated : 10/21/2003
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Kelly A. Przylepa : 6/5/2002
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carol : 03/28/2023<br>carol : 03/27/2023<br>carol : 03/23/2023<br>carol : 11/15/2022<br>carol : 11/14/2022<br>alopez : 11/10/2022<br>carol : 01/13/2022<br>carol : 07/07/2021<br>carol : 05/30/2018<br>alopez : 05/29/2018<br>alopez : 05/29/2018<br>carol : 07/14/2016<br>carol : 7/9/2016<br>carol : 7/9/2016<br>carol : 4/18/2016<br>carol : 4/18/2016<br>alopez : 4/8/2015<br>carol : 8/30/2013<br>alopez : 10/4/2012<br>alopez : 10/4/2012<br>carol : 8/3/2012<br>carol : 7/3/2012<br>mgross : 12/16/2011<br>wwang : 7/22/2011<br>terry : 4/21/2011<br>terry : 1/13/2011<br>wwang : 8/18/2010<br>ckniffin : 8/16/2010<br>joanna : 6/29/2010<br>wwang : 11/6/2009<br>terry : 10/30/2009<br>wwang : 9/9/2009<br>terry : 4/3/2009<br>carol : 10/1/2007<br>wwang : 8/1/2007<br>ckniffin : 7/25/2007<br>wwang : 11/13/2006<br>terry : 11/10/2006<br>carol : 11/30/2005<br>terry : 3/3/2005<br>tkritzer : 8/4/2004<br>ckniffin : 8/3/2004<br>ckniffin : 8/3/2004<br>tkritzer : 5/19/2004<br>terry : 5/18/2004<br>carol : 1/14/2004<br>cwells : 1/5/2004<br>carol : 10/28/2003<br>alopez : 10/21/2003<br>carol : 10/17/2003<br>carol : 10/17/2003<br>terry : 10/17/2003<br>carol : 10/17/2003<br>carol : 10/10/2003<br>carol : 10/8/2003<br>carol : 10/6/2003
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