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- #248500 - MANNOSIDOSIS, ALPHA B, LYSOSOMAL; MANSA
- OMIM
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<span class="h4">#248500</span>
<br />
<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/248500"><strong>Clinical Synopsis</strong></a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#diagnosis">Diagnosis</a>
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<a href="#clinicalManagement">Clinical Management</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="#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="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=MANNOSIDOSIS, ALPHA B, LYSOSOMAL" 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>
<div><a href="#mimEuroGentestFold" id="mimEuroGentestToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A list of European laboratories that offer genetic testing."><span id="mimEuroGentestToggleTriangle" class="small" style="margin-left: -0.8em;">&#9658;</span>EuroGentest</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=21366&Typ=Pat" title="Alpha-mannosidosis, infantile form" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Alpha-mannosidosis, infant…&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=21367&Typ=Pat" title="Alpha-mannosidosis, adult form" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Alpha-mannosidosis, adult …&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=3&Typ=Pat" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Alpha-mannosidosis&nbsp;</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1396/" 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 style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=309282" title="Alpha-mannosidosis, infantile form" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Alpha-mannosidosis, infant…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=309288" title="Alpha-mannosidosis, adult form" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Alpha-mannosidosis, adult …</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=61" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Alpha-mannosidosis</a></div>
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<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/bbf12c68-cead-4655-a7c6-d2cbd7b00c48/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>
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<div><a href="https://www.alliancegenome.org/disease/DOID:3413" 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/248500" 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>
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<div><a href="https://wormbase.org/resources/disease/DOID:3413" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Cell Lines</div>
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<div class="panel-body small mim-panel-body">
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:248500" 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>
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<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;
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<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> 124466001, 65524005<br />
<strong>ORPHA:</strong> 309282, 309288, 61<br />
<strong>DO:</strong> 3413<br />
">ICD+</a>
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<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
248500
</span>
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<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
MANNOSIDOSIS, ALPHA B, LYSOSOMAL; MANSA
</span>
</h3>
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<br />
</div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
ALPHA-MANNOSIDOSIS<br />
LYSOSOMAL ALPHA-D-MANNOSIDASE DEFICIENCY<br />
ALPHA-MANNOSIDASE B DEFICIENCY
</span>
</h4>
</div>
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<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
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<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
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<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/19/326?start=-3&limit=10&highlight=326">
19p13.13
</a>
</span>
</td>
<td>
<span class="mim-font">
Mannosidosis, alpha-, types I and II
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/248500"> 248500 </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">
MAN2B1
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/609458"> 609458 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
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<a href="/clinicalSynopsis/248500" class="btn btn-warning" role="button"> Clinical Synopsis </a>
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PheneGene Graphics <span class="caret"></span>
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<li><a href="/graph/linear/248500" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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</ul>
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<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>
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<p />
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<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> Other </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Growth retardation in severe cases <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855407&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855407</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 /> -
Flat occiput <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837402&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837402</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005469" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005469</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005469" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005469</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0784fc0f45522e9726984768f3b187c7" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Occiput,Flat-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=0784fc0f45522e9726984768f3b187c7&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 facies <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><br /> -
Broad forehead <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849089&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849089</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000337" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000337</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000337" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000337</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=40e77945a1b2a5742a89317aeb604f00" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Forehead,Broad-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=40e77945a1b2a5742a89317aeb604f00&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 /> -
Frontal bossing <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/90145001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">90145001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221354&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221354</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002007</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=3ab8802347404fb5ebf087fa6440bb25" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Frontal_Bossing-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=3ab8802347404fb5ebf087fa6440bb25&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 /> -
Midface hypoplasia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853242&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853242</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011800" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011800</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011800" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011800</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=f0adae8ae2dc0ad9ed28c3c3e0e8f8a9" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Midface_Retrusion-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=f0adae8ae2dc0ad9ed28c3c3e0e8f8a9&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 /> -
Prognathism <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/72855002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">72855002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/109504005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">109504005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22810007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22810007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M26.213" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M26.213</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/524.23" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">524.23</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0399526&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0399526</a>, <a href="https://bioportal.bioontology.org/search?q=C0033324&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0033324</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000303" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000303</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000303" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000303</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=2aaef6d7371d3478c5adcef40ea1e36f" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Prognathism-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=2aaef6d7371d3478c5adcef40ea1e36f&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">
- Sensorineural deafness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/60700002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">60700002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H90.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H90.5</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/389.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.10</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/389.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018784&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018784</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000407" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000407</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000407" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000407</a>]</span><br /> -
Large ears <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/275480001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">275480001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0554972&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0554972</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000400" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000400</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000400" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000400</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">
- Epicanthal folds <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/74824007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">74824007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0678230&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0678230</a>, <a href="https://bioportal.bioontology.org/search?q=C0229249&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0229249</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000286" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000286</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000286" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000286</a>]</span><br /> -
Heavy eyebrows <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853487&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853487</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000574" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000574</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000574" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000574</a>]</span><br /> -
Lenticular 'spoke-like' opacities <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855410&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855410</a>]</span><br /> -
Retinal degeneration in adult patients, progressive <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855411&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855411</a>]</span><br /> -
Impaired smooth pursuit in adult patients <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855412&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855412</a>]</span><br /> -
Nystagmus in adult patients <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855413&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855413</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">
- Flat nose <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1842876&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1842876</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000457" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000457</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000457" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000457</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=6177d3a4fab7cfab6ced65cf65caf77a" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Nasal_Ridge,Depressed-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=6177d3a4fab7cfab6ced65cf65caf77a&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">
- Macroglossia <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> <span class="mim-feature-ids hidden">[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> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=ac5acf24e74116d49a4df85084887155" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Tongue,Large-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=ac5acf24e74116d49a4df85084887155&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 /> -
Gingival 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> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=e4e28205bf42ed5b9f7c80e5ea624dec" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Gingival_Overgrowth-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=e4e28205bf42ed5b9f7c80e5ea624dec&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> Teeth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Widely-spaced teeth <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1844813&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1844813</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000687" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000687</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000687" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000687</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> External Features </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Pectus carinatum <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/205101001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">205101001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/38774000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">38774000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q67.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q67.7</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/754.82" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">754.82</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2939416&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2939416</a>, <a href="https://bioportal.bioontology.org/search?q=C0158731&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0158731</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000768" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000768</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000768" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000768</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Ribs Sternum Clavicles & Scapulae </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Thick, undertubulated ribs <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855406&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855406</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> 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 (in some patients) <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">
- 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">
- Thickening of the calvaria <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1858452&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858452</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002684" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002684</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002684" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002684</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">
- Abnormal vertebral bodies (ovoid, flat, beaked) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855416&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855416</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003312" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003312</a>]</span><br /> -
Increased vertebral height <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1864853&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1864853</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004570" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004570</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004570" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004570</a>]</span><br /> -
Thoracolumbar gibbus deformity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855418&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855418</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005619" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005619</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005619" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005619</a>]</span><br /> -
Spondylolisthesis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/274152003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">274152003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/13236000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">13236000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/203681002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">203681002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M43.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M43.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q76.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q76.2</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M43.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M43.10</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/738.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">738.4</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/756.12" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">756.12</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038017&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038017</a>, <a href="https://bioportal.bioontology.org/search?q=C2242765&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2242765</a>, <a href="https://bioportal.bioontology.org/search?q=C0038016&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038016</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003302" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003302</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003302" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003302</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">
- Bowed femurs <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1859461&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1859461</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002980" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002980</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002980" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002980</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> Hair </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hypertrichosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/29966009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">29966009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/271607001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">271607001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/L68" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L68</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/L68.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L68.3</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/L68.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L68.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020555&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020555</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000998" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000998</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000998" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000998</a>]</span><br /> -
Low anterior hairline <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1842366&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1842366</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000294" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000294</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000294" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000294</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=65b0191a33ac10e07bf69640f20cfc40" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Hairline,Low_Anterior-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=65b0191a33ac10e07bf69640f20cfc40&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 /> -
Anterior hair whorl <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855421</a>]</span><br /> -
Heavy eyebrows <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853487&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853487</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000574" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000574</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000574" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000574</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">
- Delayed psychomotor development <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/224958001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">224958001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F88</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0557874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0557874</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span><br /> -
Mental retardation from rapid mental regression <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855397&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855397</a>]</span><br /> -
Hypotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398151007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398151007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398152000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398152000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026827&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026827</a>, <a href="https://bioportal.bioontology.org/search?q=C1858120&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858120</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001290</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span><br /> -
Impaired speech <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/29164008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">29164008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/162294008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">162294008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R47.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R47.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0233715&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0233715</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000750" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000750</a>]</span><br /> -
Nerve cells show ballooning with membrane-bound vesicles with reticulogranular pattern <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855398&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855398</a>]</span><br /> -
Corticospinal tract disease in lower limbs (in adulthood) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855399&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855399</a>]</span><br /> -
Spinocerebellar tract disease in lower limbs (in adulthood) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855400&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855400</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007232" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007232</a>]</span><br /> -
Gait ataxia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/25136009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">25136009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R26.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R26.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0751837&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0751837</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002066" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002066</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002066" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002066</a>]</span><br /> -
Limb ataxia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0750937&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0750937</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002070" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002070</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002070" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002070</a>]</span><br /> -
Spasticity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/221360009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">221360009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/397790002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">397790002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026838&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026838</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001257" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001257</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001257" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001257</a>]</span><br /> -
Extensor plantar responses <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246586009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246586009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/366575004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">366575004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0034935&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0034935</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003487" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003487</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003487" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003487</a>]</span><br /> -
Dysarthria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8011004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8011004</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.13" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.13</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/784.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">784.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span><br /> -
Hyperreflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/86854008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">86854008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151889&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151889</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001347</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001347</a>]</span><br /> -
Nystagmus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/563001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">563001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/379.50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">379.50</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0028738&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0028738</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span><br /> -
Impaired smooth pursuit ocular movements <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836393&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836393</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000617" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000617</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000617" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000617</a>]</span><br /> -
Cerebellar atrophy (in adulthood) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3550519&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3550519</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001272" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001272</a>]</span><br /> -
White matter changes may occur (in adulthood) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855404&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855404</a>]</span><br /> -
Cerebral atrophy (in adulthood) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4315775&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4315775</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/278849000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">278849000</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002059" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002059</a>]</span><br /> -
Delayed myelination <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/135810007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">135810007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1277241&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1277241</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012448" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012448</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012448" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012448</a>]</span><br /> -
Gliosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/359580009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">359580009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/81415000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">81415000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3887640&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3887640</a>, <a href="https://bioportal.bioontology.org/search?q=C0017639&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0017639</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002171" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002171</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0002446" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002446</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002171" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002171</a>]</span><br />
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- Vacuolated lymphocytes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836855&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836855</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001922" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001922</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001922" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001922</a>]</span><br />
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- Recurrent bacterial infections <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/428875002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">428875002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1844383&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1844383</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002718" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002718</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002718" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002718</a>]</span><br /> -
Decreased serum immunoglobulin <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/119250001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">119250001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D80.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D80.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/279.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">279.00</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0086438&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0086438</a>, <a href="https://bioportal.bioontology.org/search?q=C4048270&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4048270</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004313" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004313</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004313" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004313</a>]</span><br />
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<strong> LABORATORY ABNORMALITIES </strong>
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- Increased urinary mannose-containing oligosaccharides <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855419&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855419</a>]</span><br /> -
Decreased lysosomal alpha-mannosidase activity in plasma and leukocytes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855420&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855420</a>]</span><br />
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<strong> MISCELLANEOUS </strong>
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- Wide phenotypic variability and severity<br /> -
Neurologic symptoms are progressive<br /> -
Most patients show early childhood onset after a period of normal development<br /> -
Some patients show infantile onset<br /> -
Some patients show onset later in childhood<br />
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<strong> MOLECULAR BASIS </strong>
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- Caused by mutation in the alpha-mannosidase gene (MAN2B1, <a href="/entry/609458#0001">609458.0001</a>)<br />
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<p>A number sign (#) is used with this entry because alpha-mannosidosis (MANSA) is caused by homozygous or compound heterozygous mutation in the MAN2B1 gene (<a href="/entry/609458">609458</a>) on chromosome 19p13.</p>
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<strong>Description</strong>
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<p>Alpha-mannosidosis (MANSA) is an autosomal recessive lysosomal storage disease characterized by impaired intellectual development, coarse facial features, skeletal abnormalities, hearing impairment, neurologic motor problems, and immune deficiency. Expression of the disease varies considerably, and there is a wide spectrum of clinical findings and severity. Affected children are often normal at birth and during early development. They present in early childhood with delayed psychomotor development, delayed speech, and hearing loss. Additional features include large head with prominent forehead, rounded eyebrows, flattened nasal bridge, macroglossia, widely spaced teeth, dysostosis multiplex, and motor impairment (summary by <a href="#31" class="mim-tip-reference" title="Malm, D., Nilssen, O. &lt;strong&gt;Alpha-mannosidosis.&lt;/strong&gt; Orphanet J. Rare Dis. 3: 21, 2008. Note: Electronic Article.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18651971/&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;18651971&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=18651971[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/10.1186/1750-1172-3-21&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="18651971">Malm and Nilssen, 2008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18651971" 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>Classification Systems</em></strong></p><p>
Two classification systems have been used to describe the clinical presentation of alpha-mannosidosis. The earlier system delineated a more severe 'type I,' which shows infantile onset, rapid mental deterioration, hypotonia, splenomegaly, severe dysostosis multiplex, and severe recurrent infections, often resulting in death by age 8 years. Individuals with the less severe 'type II' show normal early development with later childhood development of impaired intellectual development, hearing loss, coarse facies, neurologic deterioration, and survival well into adulthood (summary by <a href="#16" class="mim-tip-reference" title="Desnick, R. J., Sharp, H. L., Grabowski, G. A., Brunning, R. D., Quie, P. G., Sung, J. H., Gorlin, R. J., Ikonne, J. U. &lt;strong&gt;Mannosidosis: clinical, morphologic, immunologic, and biochemical studies.&lt;/strong&gt; Pediat. Res. 10: 985-996, 1976.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/995502/&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;995502&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/00006450-197612000-00008&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="995502">Desnick et al., 1976</a> and <a href="#18" class="mim-tip-reference" title="Gotoda, Y., Wakamatsu, N., Kawai, H., Nishida, Y., Matsumoto, T. &lt;strong&gt;Missense and nonsense mutations in the lysosomal alpha-mannosidase gene (MANB) in severe and mild forms of alpha-mannosidosis.&lt;/strong&gt; Am. J. Hum. Genet. 63: 1015-1024, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9758606/&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;9758606&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/302048&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="9758606">Gotoda et al., 1998</a>). A later classification system delineated 3 clinical types. Type 1 is the mildest form, with onset after age 10 years, without skeletal abnormalities and very slow progression. Type 2 is a moderate form, with onset before age 10 years, presence of skeletal abnormalities, and slow progression with development of ataxia by age 20 to 30 years. Type 3 is the severe form, with onset in early infancy, skeletal abnormalities, and obvious progression leading to early death from primary central nervous system involvement or myopathy. Most patients belong to clinical type 2 (summary by <a href="#31" class="mim-tip-reference" title="Malm, D., Nilssen, O. &lt;strong&gt;Alpha-mannosidosis.&lt;/strong&gt; Orphanet J. Rare Dis. 3: 21, 2008. Note: Electronic Article.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18651971/&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;18651971&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=18651971[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/10.1186/1750-1172-3-21&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="18651971">Malm and Nilssen, 2008</a>). Despite the clinical heterogeneity of the disorder, there are no apparent genotype/phenotype correlations (<a href="#8" class="mim-tip-reference" title="Berg, T., Riise, H. M. F., Hansen, G. M., Malm, D., Tranebjaerg, L., Tollersrud, O. K., Nilssen, O. &lt;strong&gt;Spectrum of mutations in alpha-mannosidosis.&lt;/strong&gt; Am. J. Hum. Genet. 64: 77-88, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9915946/&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;9915946&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/302183&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="9915946">Berg et al., 1999</a>; <a href="#43" class="mim-tip-reference" title="Riise Stensland, H. M. F., Klenow, H. B., Van Nguyen, L., Hansen, G. M., Malm, D., Nilssen, O. &lt;strong&gt;Identification of 83 novel alpha-mannosidosis-associated sequence variants: functional analysis of MAN2B1 missense mutations.&lt;/strong&gt; Hum. Mutat. 33: 511-520, 2012. Note: Erratum: Hum. Mutat. 37: 827 only, 2016.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22161967/&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;22161967&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.22005&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="22161967">Riise Stensland et al., 2012</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=18651971+995502+22161967+9758606+9915946" 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>Clinical Features</strong>
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<p>Ockerman (<a href="#38" class="mim-tip-reference" title="Ockerman, P. A. &lt;strong&gt;A generalized storage disorder resembling Hurler&#x27;s syndrome.&lt;/strong&gt; Lancet 290: 239-241, 1967. Note: Originally Volume 2."None>1967</a>, <a href="#39" class="mim-tip-reference" title="Ockerman, P. A. &lt;strong&gt;Mannosidosis: isolation of oligosaccharide storage material from brain.&lt;/strong&gt; J. Pediat. 75: 360-365, 1969.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4979626/&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;4979626&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(69)80259-3&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="4979626">1969</a>) reported a boy with a generalized lysosomal storage disorder resembling Hurler syndrome (<a href="/entry/607014">607014</a>), but the storage material was not acid mucopolysaccharide. The patient had coarse features, macroglossia, flat nose, large clumsy ears, widely spaced teeth, large head, big hands and feet, tall stature, lenticular opacities, muscular hypotonia, lumbar gibbus, and radiographic skeletal abnormalities. He also had mild hepatosplenomegaly, dilated cerebral ventricles, hypogammaglobulinemia, and susceptibility to infection. Vacuolated lymphocytes were present in the bone marrow and blood. The patient died at age 4.5 years during an episode of increased intracranial pressure. Histologic study showed storage material in the cerebral cortex, brainstem, spinal medulla, neurohypophysis, retina, and myenteric plexus. Total mannose in the liver was strikingly increased. Alpha-mannosidase activity in all tissues studied was abnormally low, whereas other acid hydrolases had higher than normal activities. The term 'mannosidosis' was suggested as the name of the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4979626" 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="#37" class="mim-tip-reference" title="Ockerman, P. A., Autio, S., Norder, N. E. &lt;strong&gt;Diagnosis of mannosidosis.&lt;/strong&gt; Lancet 301: 207-208, 1973. Note: Originally Volume 1.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4118828/&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;4118828&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(73)90045-7&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="4118828">Ockerman et al. (1973)</a> referred to the identification of mannosidosis in 2 Hungarian sisters and 3 Finnish boys, including 2 brothers. A procedure for the study of low molecular weight urinary compounds containing mannose was useful in the study of these cases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4118828" 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="Bach, G., Kohn, G., Lasch, E. E., Massri, M. E., Ornoy, A., Sekeles, E., Legum, C., Cohen, M. M. &lt;strong&gt;A new variant of mannosidosis with increased residual enzymatic activity and mild clinical manifestation.&lt;/strong&gt; Pediat. Res. 12: 1010-1015, 1978.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/724292/&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;724292&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/00006450-197810000-00012&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="724292">Bach et al. (1978)</a> reported 2 sibs, born of consanguineous Palestinian parents, with mild mental retardation, delayed speech, coarse facies, and limited mobility of the large joints. Cultured fibroblasts showed partial alpha-mannosidase deficiency (20% of normal), and the sibs were considered to be mildly affected. However, both patients had vacuolated leukocytes and fibroblasts consistent with the disease phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=724292" 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 cultured cell from patients with mannosidosis, <a href="#16" class="mim-tip-reference" title="Desnick, R. J., Sharp, H. L., Grabowski, G. A., Brunning, R. D., Quie, P. G., Sung, J. H., Gorlin, R. J., Ikonne, J. U. &lt;strong&gt;Mannosidosis: clinical, morphologic, immunologic, and biochemical studies.&lt;/strong&gt; Pediat. Res. 10: 985-996, 1976.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/995502/&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;995502&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/00006450-197612000-00008&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="995502">Desnick et al. (1976)</a> found defects of neutrophil function, including depressed chemotactic responsiveness and impaired phagocytosis of bacteria. They suggested that recurrent respiratory tract infections resulted from immunoglobulin deficiencies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=995502" 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="#35" class="mim-tip-reference" title="Montgomery, T. R., Thomas, G. H., Valle, D. L. &lt;strong&gt;Mannosidosis in an adult.&lt;/strong&gt; Johns Hopkins Med. J. 151: 113-117, 1982.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7109418/&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;7109418&lt;/a&gt;]" pmid="7109418">Montgomery et al. (1982)</a> found reports of about 50 cases of mannosidosis. Clinical expression varied from few symptoms to death in childhood. Most patients were in their first or second decade of life. <a href="#35" class="mim-tip-reference" title="Montgomery, T. R., Thomas, G. H., Valle, D. L. &lt;strong&gt;Mannosidosis in an adult.&lt;/strong&gt; Johns Hopkins Med. J. 151: 113-117, 1982.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7109418/&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;7109418&lt;/a&gt;]" pmid="7109418">Montgomery et al. (1982)</a> described a 32-year-old man who had been diagnosed as having a 'lipochondrodystrophy possibly Hurler syndrome' at the age of 18 months on the basis of hepatosplenomegaly, dysostosis multiplex, and coarse facies. He had a relatively mild and nonprogressive course with deafness, mental retardation, pectus carinatum, thoracolumbar gibbus, thick calvaria, and lens opacities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7109418" 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="Press, O. W., Fingert, H., Lott, I. T., Dickersin, C. R. &lt;strong&gt;Pancytopenia in mannosidosis.&lt;/strong&gt; Arch. Intern. Med. 143: 1266-1268, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6860058/&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;6860058&lt;/a&gt;]" pmid="6860058">Press et al. (1983)</a> reported a man with mannosidosis who was 33 years old in 1981 when he presented with pancytopenia. He was first seen at age 26 years with massive gingival hypertrophy, severe mental retardation, and bowed femurs. Mannose-laden histiocytes were demonstrated in the gingiva. An autoimmune basis of the pancytopenia was demonstrated by the presence of antiplatelet and antineutrophil antibodies and a low haptoglobin level. The authors speculated that abnormal accumulation of mannose-rich glycoproteins and oligosaccharides in the membranes of blood cells was responsible for the genesis of neoantigenic determinants. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6860058" 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="Michelakakis, H., Dimitriou, E., Mylona-Karayanni, C., Bartsocas, C. S. &lt;strong&gt;Phenotypic variability of mannosidosis type II: report of two Greek siblings.&lt;/strong&gt; Genetic Counseling 3: 195-199, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1472354/&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;1472354&lt;/a&gt;]" pmid="1472354">Michelakakis et al. (1992)</a> described a 13-year-old Greek boy and his 24-year-old sister with type II mannosidosis. Both had mental retardation, sensorineural deafness, and reduced mannosidase levels in plasma and white blood cells. The boy had normal physical and psychomotor development until age 2 when progressive mental regression set in. He also had frequent respiratory infections. He had coarse facial features with thick eyebrows, widely spaced incisors, prognathism, and a low hairline anteriorly. Radiologic survey of the skeleton showed spondylolysis with spondylolisthesis of L5 on S1. The sister had heavy eyebrows and prognathism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1472354" 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="Bennet, J. K., Dembure, P. P., Elsas, L. J. &lt;strong&gt;Clinical and biochemical analysis of two families with type I and type II mannosidosis.&lt;/strong&gt; Am. J. Med. Genet. 55: 21-26, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7702090/&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;7702090&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320550108&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="7702090">Bennet et al. (1995)</a> reported 2 unrelated patients with different presentations of mannosidosis. One had onset in early childhood with a severe phenotype characteristic of type I mannosidosis, whereas the other was diagnosed in late adulthood after the onset of progressive neurologic deterioration, consistent with type II mannosidosis. Both were detected by urinary screening of oligosaccharides. Lysosomal alpha-mannosidase activity was markedly reduced in lymphoblasts transformed from both patients' blood cells. Kinetic analyses showed that the enzyme from the type I patient had a 400-fold reduction in affinity, while that from the type II patient was reduced 40-fold. All 4 parents had reduced alpha-mannosidase activity in lymphoblasts. The type I patient had a large hydrocele and bilateral inguinal hernias at birth. Coarse facial appearance and delays in speech development prompted referral at age 13 months. At that time, hepatosplenomegaly and cataracts were noted, together with a broad forehead, frontal bossing, flat occiput, midfacial hypoplasia, epicanthal folds, hypertrichosis, and an anterior hair whorl. Brain scans showed increased ventricular size and macrocephaly. Foamy cytoplasm within vacuolated lymphocytes were demonstrated by bone marrow studies. The woman with type II mannosidosis was said to have a normal phenotype during early childhood, but required special education from the second grade onward. She learned to read and write and was independent until age 25 years when she developed bowel incontinence. Evidence of corticospinal and spinocerebellar tract disease progressed over the ensuing 15 years and was more pronounced in the lower limbs. Cerebrocortical atrophy was first documented at age 35. The diagnosis of mannosidosis was made at the age of 40. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7702090" 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="Gotoda, Y., Wakamatsu, N., Kawai, H., Nishida, Y., Matsumoto, T. &lt;strong&gt;Missense and nonsense mutations in the lysosomal alpha-mannosidase gene (MANB) in severe and mild forms of alpha-mannosidosis.&lt;/strong&gt; Am. J. Hum. Genet. 63: 1015-1024, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9758606/&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;9758606&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/302048&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="9758606">Gotoda et al. (1998)</a> reported a Japanese woman with alpha-mannosidosis confirmed by genetic analysis (<a href="/entry/609458#0002">609458.0002</a>). From the age of 1 year she had suffered from recurrent infections, such as bronchitis and otitis media. Hearing loss and delayed psychomotor development were noted at age 2 years. At the age of 9 years she entered a school for the deaf, where she did poorly. She gradually developed gait disturbance. Physical examination at the age of 36 years showed an IQ of 19, coarse facies, retinal degeneration, sensorineural hearing loss, increased deep tendon reflexes, spastic gait, and mild limb ataxia. There were vacuolated lymphocytes in her peripheral blood. Similar vacuoles were also found in biopsied muscle cells and fibroblasts. Lysosomal alpha-mannosidase activity of peripheral leukocytes was decreased to less than 1% of normal controls, whereas other lysosomal enzyme activities were all within the normal range. Thin-layer chromatography showed increased urinary excretion of oligosaccharides. A younger sister, aged 42, had a clinical history and features similar to those of the patient; pathologic examination of muscle from this sister had been reported by <a href="#25" class="mim-tip-reference" title="Kawai, H., Nishino, H., Nishida, Y., Yoneda, K., Yoshida, Y., Inui, T., Masuda, K., Saito, S. &lt;strong&gt;Skeletal muscle pathology of mannosidosis in two siblings with spastic paraplegia.&lt;/strong&gt; Acta Neuropath. 68: 201-204, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4082921/&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;4082921&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00690195&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="4082921">Kawai et al. (1985)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4082921+9758606" 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 patient with alpha-mannosidosis originally reported by <a href="#3" class="mim-tip-reference" title="Autio, S., Norden, N. E., Ockerman, P. A., Riekkinen, P., Rapola, J., Louhimo, T. &lt;strong&gt;Mannosidosis: clinical, fine-structural and biochemical findings in three cases.&lt;/strong&gt; Acta Paediat. Scand. 62: 555-565, 1973.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4358183/&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;4358183&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1651-2227.1973.tb17065.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="4358183">Autio et al. (1973)</a>, <a href="#18" class="mim-tip-reference" title="Gotoda, Y., Wakamatsu, N., Kawai, H., Nishida, Y., Matsumoto, T. &lt;strong&gt;Missense and nonsense mutations in the lysosomal alpha-mannosidase gene (MANB) in severe and mild forms of alpha-mannosidosis.&lt;/strong&gt; Am. J. Hum. Genet. 63: 1015-1024, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9758606/&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;9758606&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/302048&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="9758606">Gotoda et al. (1998)</a> identified compound heterozygosity for 2 mutations in the MAN2B1 gene (<a href="/entry/609458#0003">609458.0003</a>; <a href="/entry/609458#0004">609458.0004</a>). The patient was the only child of healthy, nonconsanguineous parents. He had recurring infections during the first year of life. By age 17 months he was speaking only a few words and impaired hearing was suspected. He had coarse facial features, delayed psychomotor functions, and brisk tendon reflexes. Approximately 80% of his peripheral blood leukocytes were vacuolated, and his alpha-mannosidase activity was reduced to approximately 2% of normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4358183+9758606" 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="Gutschalk, A., Harting, I., Cantz, M., Springer, C., Rohrschneider, K., Meinck, H.-M. &lt;strong&gt;Adult alpha-mannosidosis: clinical progression in the absence of demyelination.&lt;/strong&gt; Neurology 63: 1744-1746, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15534274/&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;15534274&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.wnl.0000143057.25471.4f&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="15534274">Gutschalk et al. (2004)</a> reported 3 adult sibs, aged 38 to 47 years, with alpha-mannosidosis. In late adolescence, all 3 developed progressive cerebellar ataxia characterized by gait ataxia, impaired smooth pursuit, nystagmus, dysarthria, and extensor plantar responses. All also had sensorineural deafness from early childhood and developed progressive retinal degeneration during late adolescence. One patient reported delusions and hallucinations. MRI showed cerebellar atrophy and periventricular white matter changes. MR spectroscopy showed no evidence of demyelination, and <a href="#20" class="mim-tip-reference" title="Gutschalk, A., Harting, I., Cantz, M., Springer, C., Rohrschneider, K., Meinck, H.-M. &lt;strong&gt;Adult alpha-mannosidosis: clinical progression in the absence of demyelination.&lt;/strong&gt; Neurology 63: 1744-1746, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15534274/&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;15534274&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.wnl.0000143057.25471.4f&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="15534274">Gutschalk et al. (2004)</a> concluded that the neurodegeneration in adult mannosidosis results from lysosomal accumulation of storage material. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15534274" 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="Courtney, R. J., Pennesi, M. E. &lt;strong&gt;Retinal dystrophy in 2 brothers with alpha-mannosidosis.&lt;/strong&gt; Arch. Ophthal. 129: 799-802, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21670350/&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;21670350&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archophthalmol.2011.134&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="21670350">Courtney and Pennesi (2011)</a> described the ocular findings in 2 brothers with alpha-mannosidosis. In addition to corneal and lenticular changes, the brothers had fundus changes including slightly pale optic discs (mild optic atrophy), retinal vascular attenuation, and mottled retinal pigment epithelium (RPE), most notable in the macula and surrounding the fovea. Additionally, there were numerous nummular yellow-white deposits evident at the level of the RPE. No foveal light reflex, peripapillary sparing, or bone spicule pigmentary change was found in either eye. Spectral-domain optical coherence tomography revealed retinal thinning. Fundus autofluorescence showed granular areas of hypoautofluorescence in the macula as well as in the posterior pole surrounding the optic nerve where speckled hyperautofluorescence was intermixed with hypoautofluorescent areas. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21670350" 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="#28" class="mim-tip-reference" title="Lehalle, D., Colombo, R., O&#x27;Grady, M., Heron, B., Houcinat, N., Kuentz, P., Moutton, S., Sorlin, A., Thevenon, J., Delanne, J., Gay, S., Racine, C., and 11 others. &lt;strong&gt;Hearing impairment as an early sign of alpha-mannosidosis in children with a mild phenotype: report of seven new cases.&lt;/strong&gt; Am. J. Med. Genet. 179A: 1756-1763, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/31241255/&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;31241255&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.61273&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="31241255">Lehalle et al. (2019)</a> reported 7 patients, aged 5 to 25 years, from 5 families with MANSA. All 7 patients had biallelic mutations in MAN2B1, reduced leukocyte alpha-mannosidase activity, and elevated mannose-rich oligosaccharides in the urine. All 7 were diagnosed with bilateral hearing loss, either sensorineural or mixed, in the first 8 years of life. Of the 6 patients in whom cognitive features were reported, all had mildly impaired intellectual development or learning disabilities. Skeletal abnormalities were identified in 2 patients: one had dysostosis with thickening of the cranial vault, bilateral coxa vara, irregularity of the glenoidal and acetabular cups and rib thickness, and the other had thickening and modeling anomalies of the long bone metaphyses and irregularity of the vertebral endplates. None of the patients had cognitive regression or early motor delays, and coarsened facial features were only recognized retrospectively in some of the patients. <a href="#28" class="mim-tip-reference" title="Lehalle, D., Colombo, R., O&#x27;Grady, M., Heron, B., Houcinat, N., Kuentz, P., Moutton, S., Sorlin, A., Thevenon, J., Delanne, J., Gay, S., Racine, C., and 11 others. &lt;strong&gt;Hearing impairment as an early sign of alpha-mannosidosis in children with a mild phenotype: report of seven new cases.&lt;/strong&gt; Am. J. Med. Genet. 179A: 1756-1763, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/31241255/&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;31241255&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.61273&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="31241255">Lehalle et al. (2019)</a> recommended that hearing loss, especially when associated with learning or cognitive abnormalities, should raise a possible diagnosis of alpha-mannosidosis or another lysosomal storage disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31241255" 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>Central Nervous System Abnormalities</em></strong></p><p>
<a href="#11" class="mim-tip-reference" title="Borgwardt, L., Danielsen, E. R., Thomsen, C., Mansson, J. E., Taouatas, N., Thuesen, A. M., Olsen, K. J., Fogh, J., Dali, C. I., Lund, A. M. &lt;strong&gt;Alpha-mannosidosis: characterization of CNS pathology and correlation between CNS pathology and cognitive function.&lt;/strong&gt; Clin. Genet. 89: 489-494, 2016.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/26212233/&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;26212233&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/cge.12642&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="26212233">Borgwardt et al. (2016)</a> studied central nervous system abnormalities in 34 MANSA patients ranging in age from 6 to 35 years. Ten patients underwent brain MRI and magnetic resonance spectroscopy (MRS). Brain imaging showed occipital white matter signal abnormalities in 5 of the 10 patients, and age-inappropriate myelination in 6. MRS demonstrated significantly elevated mannose complex in gray and white matter, consistent with gliosis. All 34 patients were analyzed for cerebrospinal fluid (CSF) markers: there were elevated concentrations of tau (MAPT; <a href="/entry/157140">157140</a>), GFAP (<a href="/entry/137780">137780</a>), and NEFL (<a href="/entry/162280">162280</a>) in 97%, 74%, and 41% of CSF samples, respectively. There was a negative correlation between CSF-biomarkers and cognitive function and CSF-oligosaccharides and cognitive function. The data indicated that the disorder is associated with early neuropathologic changes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26212233" 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="Majovska, J., Nestrasil, I., Paulson, A., Nascene, D., Jurickova, K., Hlavata, A., Lund, T., Orchard, P. J., Vaneckova M., Zeman, J., Magner, M., Dusek, P. &lt;strong&gt;White matter alteration and cerebellar atrophy are hallmarks of brain MRI in alpha-mannosidosis.&lt;/strong&gt; Molec. Genet. Metab. 132: 189-197, 2021.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/33317989/&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;33317989&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2020.11.008&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="33317989">Majovska et al. (2021)</a> reported MRI findings from 13 untreated patients with MANSA. The patients ranged in age from 13 months to 17 years, with a median age of 17 years. A total of 22 MRIs were available; 7 patients had 1 MRI and 6 patients had 2 or more. Focal and/or diffuse hyperintense signals in the cerebral white matter were present in 85% of patients. Cerebellar atrophy was seen in 62%, as early as 5 years of age. Cortical atrophy was seen in 62% and corpus callosum thinning was seen in 23%. Other findings included enlargement of white matter perivascular spaces in 38%, widening of perioptic CSF spaces in 62%, and enlargement of the cisterna magna in 85%. Progression of MRI abnormalities, including progression of cerebral and/or cerebellar atrophy, was observed in 2 of 6 patients who had serial studies. Previously reported findings of hypointensity of the basal ganglia and thalami in patients with MANSA were not identified in this study. The most frequent non-CNS abnormalities were diploic space thickening seen in 100% and mucosal thickening seen in 69%. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33317989" 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="#32" class="mim-tip-reference" title="Matlach, J., Zindel, T., Amraoui, Y., Arash-Kaps, L., Hennermann, J. B., Pitz, S. &lt;strong&gt;Retinal and optic nerve degeneration in alpha-mannosidosis.&lt;/strong&gt; Orphanet J. Rare Dis. 13: 88, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29859105/&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;29859105&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=29859105[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/10.1186/s13023-018-0829-z&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="29859105">Matlach et al. (2018)</a> reviewed ophthalmologic findings in 32 patients with alpha-mannosidosis. Six patients had strabismus, 2 had cataracts, 2 had corneal gaze, 4 had nystagmus, and 5 had impaired saccades. Fundus abnormalities included optic nerve atrophy in 6 patients (which was partial in 4) and tapetoretinal degeneration with bone spicule formations in 3 patients. Four of 7 patients who were treated with enzyme replacement therapy with velmanase alfa developed retinal degeneration despite ERT treatment. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29859105" 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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<strong>Diagnosis</strong>
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<p><a href="#19" class="mim-tip-reference" title="Guffon, N., Tylki-Szymanska, A., Borgwardt, L., Lund, A. M., Gil-Campos, M., Parini, R., Hennermann, J. B. &lt;strong&gt;Recognition of alpha-mannosidosis in paediatric and adult patients: presentation of a diagnostic algorithm from an international working group.&lt;/strong&gt; Molec. Genet. Metab. 126: 470-474, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/30792122/&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;30792122&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2019.01.024&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="30792122">Guffon et al. (2019)</a> proposed diagnostic algorithms for alpha-mannosidosis based on the consensus opinion of an expert panel. They suggested that the most prominent signs that should prompt investigation for this disease in patients 10 years of age and younger include speech delay, hearing loss, developmental delay, and facial dysmorphism. In patients older than 10 years, the most prominent signs include hearing loss, ataxia, psychiatric disturbances, and skeletal abnormalities. <a href="#19" class="mim-tip-reference" title="Guffon, N., Tylki-Szymanska, A., Borgwardt, L., Lund, A. M., Gil-Campos, M., Parini, R., Hennermann, J. B. &lt;strong&gt;Recognition of alpha-mannosidosis in paediatric and adult patients: presentation of a diagnostic algorithm from an international working group.&lt;/strong&gt; Molec. Genet. Metab. 126: 470-474, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/30792122/&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;30792122&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2019.01.024&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="30792122">Guffon et al. (2019)</a> suggested that enzyme screening in dried blood spot or leukocytes should be the first screening method, followed by confirmatory molecular testing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30792122" 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="#51" class="mim-tip-reference" title="Wiesinger, T., Schwarz, M., Mechtler, T. P., Liebmann-Reindl, S., Streubel, B., Kasper, D. C. &lt;strong&gt;Alpha-mannosidosis--an underdiagnosed lysosomal storage disease in individuals with an &#x27;MPS-like&#x27; phenotype.&lt;/strong&gt; Molec. Genet. Metab. 130: 149-152, 2020.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/32331969/&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;32331969&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2020.04.001&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="32331969">Wiesinger et al. (2020)</a> performed a tandem mass spectrometry enzyme assay for alpha-mannosidosis activity, followed by next-generation sequencing, in 835 dried blood spots from patients with suspected mucopolysaccharidoses (MPS; see, e.g., <a href="/entry/607014">607014</a>) but who had negative testing for MPS disorders. They identified 4 patients with alpha-mannosidosis and biallelic mutations in the MAN2B1 gene. <a href="#51" class="mim-tip-reference" title="Wiesinger, T., Schwarz, M., Mechtler, T. P., Liebmann-Reindl, S., Streubel, B., Kasper, D. C. &lt;strong&gt;Alpha-mannosidosis--an underdiagnosed lysosomal storage disease in individuals with an &#x27;MPS-like&#x27; phenotype.&lt;/strong&gt; Molec. Genet. Metab. 130: 149-152, 2020.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/32331969/&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;32331969&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2020.04.001&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="32331969">Wiesinger et al. (2020)</a> concluded that alpha-mannosidosis should be considered in patients who are being evaluated for MPS disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32331969" 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>
<a href="#40" class="mim-tip-reference" title="Poenaru, L., Girard, S., Thepot, F., Madelenat, P., Huraux-Rendu, C., Vinet, M.-C., Dreyfus, J.-C. &lt;strong&gt;Antenatal diagnosis in three pregnancies at risk for mannosidosis.&lt;/strong&gt; Clin. Genet. 16: 428-432, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/393435/&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;393435&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1979.tb01351.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="393435">Poenaru et al. (1979)</a> reported successful prenatal diagnosis of mannosidosis in 2 at-risk families by analyzing enzyme activity of amniotic cells from the fetus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=393435" 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="clinicalManagement" class="mim-anchor"></a>
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<strong>Clinical Management</strong>
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<p><strong><em>Enzyme Replacement Therapy</em></strong></p><p>
<a href="#21" class="mim-tip-reference" title="Harmatz, P., Cattaneo, F., Ardigo, D., Geraci, S., Hennermann, J. B., Guffon, N., Lund, A., Hendriksz, C. J. Borgwardt, L. &lt;strong&gt;Enzyme replacement therapy with velmanase alfa (human recombinant alpha-mannosidase): novel global treatment response model and outcomes in patients with alpha-mannosidosis.&lt;/strong&gt; Molec. Genet. Metab. 124: 152-160, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29716835/&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;29716835&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2018.04.003&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="29716835">Harmatz et al. (2018)</a> reported the effect of enzyme replacement therapy with velmanase alfa in treating alpha-mannosidase across several clinical trials. Using a multiple variable analysis model that takes into account pharmacodynamic, functional, and quality of life domains, <a href="#21" class="mim-tip-reference" title="Harmatz, P., Cattaneo, F., Ardigo, D., Geraci, S., Hennermann, J. B., Guffon, N., Lund, A., Hendriksz, C. J. Borgwardt, L. &lt;strong&gt;Enzyme replacement therapy with velmanase alfa (human recombinant alpha-mannosidase): novel global treatment response model and outcomes in patients with alpha-mannosidosis.&lt;/strong&gt; Molec. Genet. Metab. 124: 152-160, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29716835/&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;29716835&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2018.04.003&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="29716835">Harmatz et al. (2018)</a> showed a clinically meaningful treatment effect and a continued long-term treatment effect. Within the pharmacodynamic domain, it was found that velmanase alfa showed effectiveness in reducing serum oligosaccharide load in most treated patients. There was a greater response to treatment in participants under 18 years of age compared to those greater than 18 years of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29716835" 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>Negative Reports</em></strong></p><p>
Investigators have demonstrated that zinc can stimulate residual alpha-mannosidase activity in cultured cells from patients with mannosidosis (<a href="#26" class="mim-tip-reference" title="Kistler, J. P., Lott, I. T., Kolodny, E. H., Friedman, R. B., Nersasian, R., Schnur, J., Mihm, M. C., Dvorak, A. M., Dickersin, R. &lt;strong&gt;Mannosidosis: new clinical presentation, enzyme studies, and carbohydrate analysis.&lt;/strong&gt; Arch. Neurol. 34: 45-51, 1977.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12732/&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;12732&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.1977.00500130065013&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="12732">Kistler et al., 1977</a>). <a href="#52" class="mim-tip-reference" title="Wong, L. T. K., Vallance, H., Savage, A., Davidson, A. G. F., Applegarth, D. &lt;strong&gt;Oral zinc therapy in the treatment of alpha-mannosidosis.&lt;/strong&gt; Am. J. Med. Genet. 46: 410-414, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8357013/&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;8357013&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320460413&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="8357013">Wong et al. (1993)</a> reported a trial of oral zinc therapy for 3 years in a 4-year-old boy with alpha-mannosidosis. However, after almost 10 years of follow-up of the patient on and off zinc therapy, they concluded that there was no substantial clinical improvement. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12732+8357013" 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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<strong>Biochemical Features</strong>
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<p><a href="#37" class="mim-tip-reference" title="Ockerman, P. A., Autio, S., Norder, N. E. &lt;strong&gt;Diagnosis of mannosidosis.&lt;/strong&gt; Lancet 301: 207-208, 1973. Note: Originally Volume 1.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4118828/&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;4118828&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(73)90045-7&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="4118828">Ockerman et al. (1973)</a> found that normal liver alpha-mannosidase exists in at least 3 forms, separable by DEAE cellulose chromatography. The lysosomal A and B forms were most active at pH 4.4, whereas form C was most active at pH 6.0. In 2 cases of mannosidosis, <a href="#12" class="mim-tip-reference" title="Carroll, M., Dance, N., Masson, P. K., Robinson, D., Winchester, B. G. &lt;strong&gt;Human mannosidosis--the enzymic defect.&lt;/strong&gt; Biochem. Biophys. Res. Commun. 49: 579-583, 1972.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4640377/&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;4640377&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0006-291x(72)90450-0&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="4640377">Carroll et al. (1972)</a> found that forms A and B were missing. <a href="#13" class="mim-tip-reference" title="Cheng, S. H., Malcolm, S., Pemble, S., Winchester, B. &lt;strong&gt;Purification and comparison of the structures of human liver acidic alpha-D-mannosidases A and B.&lt;/strong&gt; Biochem. J. 233: 65-72, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3954735/&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;3954735&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1042/bj2330065&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="3954735">Cheng et al. (1986)</a> found that although mannosidase A and B differed in their subunit compositions, they were immunologically identical. The authors suggested that the differences in A and B were due to differences in processing, and that both forms arise from a single locus. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4118828+4640377+3954735" 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="Ben-Yoseph, Y., DeFranco, C. L., Charrow, J., Hahn, L. C., Nadler, H. L. &lt;strong&gt;Apparently normal extracellular acidic alpha-mannosidase in fibroblast cultures from patients with mannosidosis.&lt;/strong&gt; Am. J. Hum. Genet. 34: 100-111, 1982.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7081212/&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;7081212&lt;/a&gt;]" pmid="7081212">Ben-Yoseph et al. (1982)</a> found that mannosidase activity was normal in the medium of cultured fibroblasts from patients with mannosidosis. However, incubation of the mannosidosis extracellular enzyme with either normal or patient cell lysates resulted in a partial loss of activity, whereas an additive value was observed with the normal extracellular enzyme. <a href="#6" class="mim-tip-reference" title="Ben-Yoseph, Y., DeFranco, C. L., Charrow, J., Hahn, L. C., Nadler, H. L. &lt;strong&gt;Apparently normal extracellular acidic alpha-mannosidase in fibroblast cultures from patients with mannosidosis.&lt;/strong&gt; Am. J. Hum. Genet. 34: 100-111, 1982.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7081212/&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;7081212&lt;/a&gt;]" pmid="7081212">Ben-Yoseph et al. (1982)</a> suggested that the enzymatic defect in mannosidosis is expressed only after the enzyme has been delivered to lysosomes and presumably has undergone some form of processing there. However, <a href="#13" class="mim-tip-reference" title="Cheng, S. H., Malcolm, S., Pemble, S., Winchester, B. &lt;strong&gt;Purification and comparison of the structures of human liver acidic alpha-D-mannosidases A and B.&lt;/strong&gt; Biochem. J. 233: 65-72, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3954735/&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;3954735&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1042/bj2330065&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="3954735">Cheng et al. (1986)</a> provided evidence that the enzyme secreted by mannosidosis fibroblasts was not related immunologically to lysosomal mannosidase. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3954735+7081212" 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="inheritance" class="mim-anchor"></a>
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<strong>Inheritance</strong>
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<p><a href="#36" class="mim-tip-reference" title="Nilssen, O., Berg, T., Riise, H. M. F., Ramachandran, U., Evjen, G., Hansen, G. M., Malm, D., Tranebjaerg, L., Tollersrud, O. K. &lt;strong&gt;Alpha-mannosidosis: functional cloning of the lysosomal alpha-mannosidase cDNA and identification of a mutation in two affected siblings.&lt;/strong&gt; Hum. Molec. Genet. 6: 717-726, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9158146/&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;9158146&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/6.5.717&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="9158146">Nilssen et al. (1997)</a> confirmed autosomal recessive inheritance of alpha-mannosidosis in the Palestinian sibs reported by <a href="#5" class="mim-tip-reference" title="Bach, G., Kohn, G., Lasch, E. E., Massri, M. E., Ornoy, A., Sekeles, E., Legum, C., Cohen, M. M. &lt;strong&gt;A new variant of mannosidosis with increased residual enzymatic activity and mild clinical manifestation.&lt;/strong&gt; Pediat. Res. 12: 1010-1015, 1978.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/724292/&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;724292&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/00006450-197810000-00012&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="724292">Bach et al. (1978)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9158146+724292" 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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<strong>Molecular Genetics</strong>
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<p>In 2 Palestinian sibs with alpha-mannosidosis who were originally reported by <a href="#5" class="mim-tip-reference" title="Bach, G., Kohn, G., Lasch, E. E., Massri, M. E., Ornoy, A., Sekeles, E., Legum, C., Cohen, M. M. &lt;strong&gt;A new variant of mannosidosis with increased residual enzymatic activity and mild clinical manifestation.&lt;/strong&gt; Pediat. Res. 12: 1010-1015, 1978.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/724292/&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;724292&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/00006450-197810000-00012&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="724292">Bach et al. (1978)</a>, <a href="#36" class="mim-tip-reference" title="Nilssen, O., Berg, T., Riise, H. M. F., Ramachandran, U., Evjen, G., Hansen, G. M., Malm, D., Tranebjaerg, L., Tollersrud, O. K. &lt;strong&gt;Alpha-mannosidosis: functional cloning of the lysosomal alpha-mannosidase cDNA and identification of a mutation in two affected siblings.&lt;/strong&gt; Hum. Molec. Genet. 6: 717-726, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9158146/&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;9158146&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/6.5.717&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="9158146">Nilssen et al. (1997)</a> identified a homozygous mutation in the MAN2B1 gene (<a href="/entry/609458#0001">609458.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9158146+724292" 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 4 unrelated patients with alpha-mannosidosis, <a href="#18" class="mim-tip-reference" title="Gotoda, Y., Wakamatsu, N., Kawai, H., Nishida, Y., Matsumoto, T. &lt;strong&gt;Missense and nonsense mutations in the lysosomal alpha-mannosidase gene (MANB) in severe and mild forms of alpha-mannosidosis.&lt;/strong&gt; Am. J. Hum. Genet. 63: 1015-1024, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9758606/&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;9758606&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/302048&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="9758606">Gotoda et al. (1998)</a> identified homozygous or compound heterozygous mutations in the MAN2B1 gene (<a href="/entry/609458#0001">609458.0001</a>-<a href="/entry/609458#0005">609458.0005</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9758606" 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="Riise Stensland, H. M. F., Klenow, H. B., Van Nguyen, L., Hansen, G. M., Malm, D., Nilssen, O. &lt;strong&gt;Identification of 83 novel alpha-mannosidosis-associated sequence variants: functional analysis of MAN2B1 missense mutations.&lt;/strong&gt; Hum. Mutat. 33: 511-520, 2012. Note: Erratum: Hum. Mutat. 37: 827 only, 2016.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22161967/&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;22161967&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.22005&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="22161967">Riise Stensland et al. (2012)</a> identified 96 different pathogenic mutations in the MAN2B1 gene, including 83 novel mutations, in 130 unrelated patients with alpha-mannosidosis from 30 countries. Most of the mutations were private, but R750W (<a href="/entry/609458#0004">609458.0004</a>) was found in 50 patients from 16 countries and accounted for 27.3% of disease alleles. Other recurrent mutations included a splice site mutation in intron 14 (<a href="/entry/609458#0006">609458.0006</a>), found in 13 disease alleles, and L809P (<a href="/entry/609458#0007">609458.0007</a>), found in 8 disease alleles. Twenty-nine novel missense mutations were identified. Most did not show any residual enzyme activity when expressed in COS-7 cells, but 10 showed some activity, including 5 with 30% or more residual activity. There were no apparent genotype/phenotype correlations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22161967" 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="populationGenetics" class="mim-anchor"></a>
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<strong>Population Genetics</strong>
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<p><a href="#21" class="mim-tip-reference" title="Harmatz, P., Cattaneo, F., Ardigo, D., Geraci, S., Hennermann, J. B., Guffon, N., Lund, A., Hendriksz, C. J. Borgwardt, L. &lt;strong&gt;Enzyme replacement therapy with velmanase alfa (human recombinant alpha-mannosidase): novel global treatment response model and outcomes in patients with alpha-mannosidosis.&lt;/strong&gt; Molec. Genet. Metab. 124: 152-160, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29716835/&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;29716835&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2018.04.003&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="29716835">Harmatz et al. (2018)</a> stated that the prevalence of alpha-mannosidase is estimated to be as low as 1:1 million live births. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29716835" 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="Riise Stensland, H. M. F., Klenow, H. B., Van Nguyen, L., Hansen, G. M., Malm, D., Nilssen, O. &lt;strong&gt;Identification of 83 novel alpha-mannosidosis-associated sequence variants: functional analysis of MAN2B1 missense mutations.&lt;/strong&gt; Hum. Mutat. 33: 511-520, 2012. Note: Erratum: Hum. Mutat. 37: 827 only, 2016.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22161967/&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;22161967&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.22005&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="22161967">Riise Stensland et al. (2012)</a> found that the R750W mutation in the MAN2B1 gene (<a href="/entry/609458#0004">609458.0004</a>) was the most common mutation among 130 unrelated patients with alpha-mannosidosis from 30 countries. It was found in 50 patients from 16 countries and accounted for 27.3% of disease alleles. Haplotype analysis indicated at least 4 independent events causing R750W, with 1 haplotype accounting for 95% of the alleles. Population-based analysis suggested that the mutant allele arose in eastern Europe. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22161967" 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>Animal Model</strong>
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<p><a href="#22" class="mim-tip-reference" title="Hocking, J. D., Jolly, R. D., Batt, R. D. &lt;strong&gt;Deficiency of alpha-mannosidase in Angus cattle: an inherited lysosomal storage disease.&lt;/strong&gt; Biochem. J. 128: 69-78, 1972.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4673577/&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;4673577&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1042/bj1280069&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="4673577">Hocking et al. (1972)</a> described recessive inheritance of mannosidosis in cattle. The disease is manifest by head tremor, aggressive tendency, ataxia, failure to thrive, and early death. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4673577" 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="#9" class="mim-tip-reference" title="Berg, T., Tollersrud, O. K., Walkley, S. U., Siegel, D., Nilssen, O. &lt;strong&gt;Purification of feline lysosomal alpha-mannosidase, determination of its cDNA sequence and identification of a mutation causing alpha-mannosidosis in Persian cats.&lt;/strong&gt; Biochem. J. 328: 863-870, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9396732/&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;9396732&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1042/bj3280863&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="9396732">Berg et al. (1997)</a> identified a 4-bp deletion in the feline Man2b1 gene in a Persian cat with mannosidosis; the deletion resulted in a frameshift from codon 583 and premature termination at codon 645. No enzyme activity could be detected in the liver of the cat. A domestic long-haired cat expressing a milder phenotype had enzyme activity of 2% of normal; this cat did not possess the 4-bp deletion. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9396732" 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 the Man2b1 cDNA of alpha-mannosidosis-affected Angus cattle, <a href="#45" class="mim-tip-reference" title="Tollersrud, O. K., Berg, T., Healy, P., Evjen, G., Ramachandran, U., Nilssen, O. &lt;strong&gt;Purification of bovine lysosomal alpha-mannosidase, characterization of its gene and determination of two mutations that cause alpha-mannosidosis.&lt;/strong&gt; Europ. J. Biochem. 246: 410-419, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9208932/&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;9208932&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1432-1033.1997.00410.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="9208932">Tollersrud et al. (1997)</a> found a 961T-C transition, resulting in a phe321-to-leu amino acid substitution. In affected Galloway cattle, they found a 662G-A transition that caused an arg221-to-his substitution. Phe321 and arg221 are conserved among the alpha-mannosidase class-2 family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9208932" 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="#15" class="mim-tip-reference" title="Crawley, A. C., Jones, M. Z., Bonning, L. E., Finnie, J. W., Hopwood, J. J. &lt;strong&gt;Alpha-mannosidosis in the guinea pig: a new animal model for lysosomal storage disorders.&lt;/strong&gt; Pediat. Res. 46: 501-509, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10541310/&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;10541310&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/00006450-199911000-00003&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="10541310">Crawley et al. (1999)</a> identified alpha-mannosidosis in the guinea pig. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10541310" 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>Therapeutic Strategies</em></strong></p><p>
<a href="#49" class="mim-tip-reference" title="Walkley, S. U., Thrall, M. A., Dobrenis, K., Huang, M., March, P. A., Siegel, D. A., Wurzelmann, S. &lt;strong&gt;Bone marrow transplantation corrects the enzyme defect in neurons of the central nervous system in a lysosomal storage disease.&lt;/strong&gt; Proc. Nat. Acad. Sci. 91: 2970-2974, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8159689/&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;8159689&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.91.8.2970&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="8159689">Walkley et al. (1994)</a> studied the effects of bone marrow transplantation (BMT) in alpha-mannosidosis in cats where the disease shows clinical, morphologic, and biochemical features closely resembling those in the human disease. BMT-treated animals showed little or no progression of neurologic signs 1 to 2 years after transplant, whereas untreated cats became severely impaired and reached end-stage disease by 6 months of age. Increased lysosomal alpha-mannosidase activity was found in brain tissue of the treated animals, and electron microscopy demonstrated no evidence of lysosomal storage within most neurons. Histochemical localization of acidic alpha-D-mannosidase showed that functional enzyme was present in neurons, glial cells, and cells associated with blood vessels. This study provided direct evidence that bone marrow transplantation can lead to significant replacement of lysosomal hydrolase within neurons of the central nervous system and can compensate for the genetic metabolic defect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8159689" 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="#44" class="mim-tip-reference" title="Roces, D. P., Lullmann-Rauch, R., Peng, J., Balducci, C., Andersson, C., Tollersrud, O., Fogh, J., Orlacchio, A., Beccari, T., Saftig, P., von Figura, K. &lt;strong&gt;Efficacy of enzyme replacement therapy in alpha-mannosidosis mice: a preclinical animal study.&lt;/strong&gt; Hum. Molec. Genet. 13: 1979-1988, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15269179/&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;15269179&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddh220&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="15269179">Roces et al. (2004)</a> reported correction of storage of neutral oligosaccharides in a mouse model of alpha-mannosidosis after intravenous administration of Man2b1 from bovine kidney and human and mouse recombinant MAN2B1. The bovine and human enzymes were barely phosphorylated, whereas the bulk of the mouse Man2b1 contained mannose 6-phosphate recognition markers. Clearance and apparent half-life of the internalized enzyme was dependent on the enzyme source as well as tissue type. The corrective effect was time-, tissue- and dose-dependent, and the effects were observed to be transient. After a single dose injection of MAN2B1, the maximum corrective effect was observed between 2 and 6 days. Injection of 250 microU of human MAN2B1 per gram of body weight followed by a subsequent injection 3.5 days later was sufficient to clear liver, kidney, and heart of neutral oligosaccharides. A decrease in mannose-containing oligosaccharides was also observed in the brain, with storage levels in treated mice less than 30% of levels found in control mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15269179" 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="#10" class="mim-tip-reference" title="Blanz, J., Stroobants, S., Lullmann-Rauch, R., Morelle, W., Ludemann, M., D&#x27;Hooge, R., Reuterwall, H., Michalski, J. C., Fogh, J., Andersson, C., Saftig, P. &lt;strong&gt;Reversal of peripheral and central neural storage and ataxia after recombinant enzyme replacement therapy in alpha-mannosidosis mice.&lt;/strong&gt; Hum. Molec. Genet. 17: 3437-3445, 2008.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18713755/&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;18713755&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddn237&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="18713755">Blanz et al. (2008)</a> demonstrated that the neuropathology of a mouse model for alpha-mannosidosis could be efficiently treated using recombinant human alpha-mannosidase (rhLAMAN). After intravenous administration of various doses (25-500 U/kg), rhLAMAN was widely distributed among tissues, and immunohistochemistry revealed lysosomal delivery of the injected enzyme. Whereas low doses (25 U/kg) led to a greater than 70% clearance of stored substrates in visceral tissues and doses of 250 U/kg were sufficient for clearance in peripheral neurons of the trigeminal ganglion, repeated high-dose injections (500 U/kg) were required to achieve a greater than 50% reduction of brain storage. Successful transfer across the blood-brain barrier was evident as the injected enzyme was found in hippocampal neurons, leading to nearly complete disappearance of storage vacuoles. In addition, the decrease in neuronal storage in the brain correlated with an improvement of the neuromotor disabilities found in untreated alpha-mannosidosis mice. Uptake of rhLAMAN seemed to be independent of mannose-6-phosphate receptors, consistent with the low phosphorylation profile of the enzyme. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18713755" 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 href="#Arbisser1976" class="mim-tip-reference" title="Arbisser, A. I., Murphree, A. L., Garcia, C. A., Howell, R. R. &lt;strong&gt;Ocular findings in mannosidosis.&lt;/strong&gt; Am. J. Ophthal. 82: 465-471, 1976.">Arbisser et al. (1976)</a>; <a href="#Autio1982" class="mim-tip-reference" title="Autio, S., Louhimo, T., Helenius, M. &lt;strong&gt;The clinical course of mannosidosis.&lt;/strong&gt; Ann. Clin. Res. 14: 93-97, 1982.">Autio et al. (1982)</a>; <a href="#Aylsworth1976" class="mim-tip-reference" title="Aylsworth, A. S., Taylor, H. A., Stuart, C. M., Thomas, G. H. &lt;strong&gt;Mannosidosis: phenotype of a severely affected child and characterization of alpha-mannosidase activity in cultured fibroblasts from the patient and his parents.&lt;/strong&gt; J. Pediat. 88: 814-818, 1976.">Aylsworth et al. (1976)</a>; <a href="#Gordon1980" class="mim-tip-reference" title="Gordon, B. A., Carson, R., Haust, M. D. &lt;strong&gt;Unusual clinical and ultrastructural features in a boy with biochemically typical mannosidosis.&lt;/strong&gt; Acta Paediat. Scand. 69: 787-792, 1980.">Gordon et al. (1980)</a>; <a href="#Hultberg1970" class="mim-tip-reference" title="Hultberg, B. &lt;strong&gt;Properties of alpha-mannosidase in mannosidosis.&lt;/strong&gt; Scand. J. Clin. Lab. Invest. 26: 155-160, 1970.">Hultberg (1970)</a>; <a href="#Jolly1980" class="mim-tip-reference" title="Jolly, R. D., Slack, P. M., Winter, P. J., Murphy, C. E. &lt;strong&gt;Mannosidosis: patterns of storage and urinary excretion of oligosaccharides in the bovine model.&lt;/strong&gt; Aust. J. Exp. Biol. Med. Sci. 58: 421-428, 1980.">Jolly et al. (1980)</a>; <a href="#Kjellman1969" class="mim-tip-reference" title="Kjellman, B., Gamstorp, I., Brun, A., Ockerman, P. A., Palmgren, B. &lt;strong&gt;Mannosidosis: a clinical and histopathologic study.&lt;/strong&gt; J. Pediat. 75: 366-373, 1969.">Kjellman
et al. (1969)</a>; <a href="#Mali1976" class="mim-tip-reference" title="Mali, J. W. H., Bergers, A. M. G., Van den Hurk, J. J. M. A., Mier, P. D., Van de Staak, W. J. B. M. &lt;strong&gt;A lysosomal storage disorder of the epidermis characterized by a deficiency of alpha-mannosidase and an accumulation of mannose-rich materials.&lt;/strong&gt; Brit. J. Derm. 95: 627-630, 1976.">Mali et al. (1976)</a>; <a href="#Mitchell1981" class="mim-tip-reference" title="Mitchell, M. L., Erickson, R. P., Schmid, D., Hieber, V., Poznanski, A. K., Hicks, S. P. &lt;strong&gt;Mannosidosis: two brothers with different degrees of disease severity.&lt;/strong&gt; Clin. Genet. 20: 191-202, 1981.">Mitchell et al. (1981)</a>; <a href="#Poenaru1980" class="mim-tip-reference" title="Poenaru, L., Miranda, C., Dreyfus, J.-C. &lt;strong&gt;Residual mannosidase activity in human mannosidosis: characterization of the mutant enzyme.&lt;/strong&gt; Am. J. Hum. Genet. 32: 354-363, 1980.">Poenaru et
al. (1980)</a>; <a href="#Tsay1975" class="mim-tip-reference" title="Tsay, G. C., Dawson, G., Matalon, R. &lt;strong&gt;Glycopeptide storage in skin fibroblasts cultured from a patient with alpha-mannosidase deficiency.&lt;/strong&gt; J. Clin. Invest. 56: 711-718, 1975.">Tsay et al. (1975)</a>; <a href="#Vandevelde1982" class="mim-tip-reference" title="Vandevelde, M., Fankhauser, R., Bichsel, P., Wiesmann, U., Herschkowitz, N. &lt;strong&gt;Hereditary neurovisceral mannosidosis associated with alpha-mannosidase deficiency in a family of Persian cats.&lt;/strong&gt; Acta Neuropath. 58: 64-68, 1982.">Vandevelde et al. (1982)</a>; <a href="#Vidgoff1977" class="mim-tip-reference" title="Vidgoff, J., Lovrien, E. W., Beals, R. K., Buist, N. R. M. &lt;strong&gt;Mannosidosis in three brothers--a review of the literature.&lt;/strong&gt; Medicine 56: 335-348, 1977.">Vidgoff et
al. (1977)</a>; <a href="#Warner1984" class="mim-tip-reference" title="Warner, T. G., Mock, A. K., Nyhan, W. L., O&#x27;Brien, J. S. &lt;strong&gt;Alpha-mannosidosis: analysis of urinary oligosaccharides with high performance liquid chromatography and diagnosis of a case with unusually mild presentation.&lt;/strong&gt; Clin. Genet. 25: 248-255, 1984.">Warner et al. (1984)</a>; <a href="#Yunis1976" class="mim-tip-reference" title="Yunis, J. J., Lewandowski, R. C., Jr., Sanfilippo, S. J., Tsai, M. Y., Foni, I., Bruhl, H. H. &lt;strong&gt;Clinical manifestations of mannosidosis--a longitudinal study.&lt;/strong&gt; Am. J. Med. 61: 841-848, 1976.">Yunis et al. (1976)</a>
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<a id="references"class="mim-anchor"></a>
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<a id="Arbisser1976" class="mim-anchor"></a>
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Arbisser, A. I., Murphree, A. L., Garcia, C. A., Howell, R. R.
<strong>Ocular findings in mannosidosis.</strong>
Am. J. Ophthal. 82: 465-471, 1976.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/961797/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">961797</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=961797" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0002-9394(76)90496-7" target="_blank">Full Text</a>]
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<a id="Autio1982" class="mim-anchor"></a>
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<p class="mim-text-font">
Autio, S., Louhimo, T., Helenius, M.
<strong>The clinical course of mannosidosis.</strong>
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Autio, S., Norden, N. E., Ockerman, P. A., Riekkinen, P., Rapola, J., Louhimo, T.
<strong>Mannosidosis: clinical, fine-structural and biochemical findings in three cases.</strong>
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[<a href="https://doi.org/10.1111/j.1651-2227.1973.tb17065.x" target="_blank">Full Text</a>]
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Aylsworth, A. S., Taylor, H. A., Stuart, C. M., Thomas, G. H.
<strong>Mannosidosis: phenotype of a severely affected child and characterization of alpha-mannosidase activity in cultured fibroblasts from the patient and his parents.</strong>
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[<a href="https://doi.org/10.1016/s0022-3476(76)81120-1" target="_blank">Full Text</a>]
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<strong>A new variant of mannosidosis with increased residual enzymatic activity and mild clinical manifestation.</strong>
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[<a href="https://doi.org/10.1203/00006450-197810000-00012" target="_blank">Full Text</a>]
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<strong>Apparently normal extracellular acidic alpha-mannosidase in fibroblast cultures from patients with mannosidosis.</strong>
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<strong>Clinical and biochemical analysis of two families with type I and type II mannosidosis.</strong>
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[<a href="https://doi.org/10.1002/ajmg.1320550108" target="_blank">Full Text</a>]
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<strong>Spectrum of mutations in alpha-mannosidosis.</strong>
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[<a href="https://doi.org/10.1086/302183" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1042/bj3280863" target="_blank">Full Text</a>]
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Blanz, J., Stroobants, S., Lullmann-Rauch, R., Morelle, W., Ludemann, M., D'Hooge, R., Reuterwall, H., Michalski, J. C., Fogh, J., Andersson, C., Saftig, P.
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[<a href="https://doi.org/10.1093/hmg/ddn237" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/cge.12642" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0006-291x(72)90450-0" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1042/bj2330065" target="_blank">Full Text</a>]
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<strong>Retinal dystrophy in 2 brothers with alpha-mannosidosis.</strong>
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[<a href="https://doi.org/10.1001/archophthalmol.2011.134" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1203/00006450-199911000-00003" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1203/00006450-197612000-00008" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1111/j.1651-2227.1980.tb07154.x" target="_blank">Full Text</a>]
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<strong>Missense and nonsense mutations in the lysosomal alpha-mannosidase gene (MANB) in severe and mild forms of alpha-mannosidosis.</strong>
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[<a href="https://doi.org/10.1086/302048" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2019.01.024" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1212/01.wnl.0000143057.25471.4f" target="_blank">Full Text</a>]
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<strong>Enzyme replacement therapy with velmanase alfa (human recombinant alpha-mannosidase): novel global treatment response model and outcomes in patients with alpha-mannosidosis.</strong>
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[<a href="https://doi.org/10.1016/j.ymgme.2018.04.003" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1042/bj1280069" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.3109/00365517009049228" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/icb.1980.43" target="_blank">Full Text</a>]
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<strong>Skeletal muscle pathology of mannosidosis in two siblings with spastic paraplegia.</strong>
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[<a href="https://doi.org/10.1007/BF00690195" target="_blank">Full Text</a>]
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Kistler, J. P., Lott, I. T., Kolodny, E. H., Friedman, R. B., Nersasian, R., Schnur, J., Mihm, M. C., Dvorak, A. M., Dickersin, R.
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[<a href="https://doi.org/10.1001/archneur.1977.00500130065013" target="_blank">Full Text</a>]
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<strong>Mannosidosis: a clinical and histopathologic study.</strong>
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[<a href="https://doi.org/10.1016/s0022-3476(69)80260-x" target="_blank">Full Text</a>]
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<strong>Hearing impairment as an early sign of alpha-mannosidosis in children with a mild phenotype: report of seven new cases.</strong>
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[<a href="https://doi.org/10.1002/ajmg.a.61273" target="_blank">Full Text</a>]
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<strong>White matter alteration and cerebellar atrophy are hallmarks of brain MRI in alpha-mannosidosis.</strong>
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[<a href="https://doi.org/10.1016/j.ymgme.2020.11.008" target="_blank">Full Text</a>]
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<strong>A lysosomal storage disorder of the epidermis characterized by a deficiency of alpha-mannosidase and an accumulation of mannose-rich materials.</strong>
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[<a href="https://doi.org/10.1111/j.1365-2133.1976.tb07035.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1186/1750-1172-3-21" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1186/s13023-018-0829-z" target="_blank">Full Text</a>]
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<strong>Phenotypic variability of mannosidosis type II: report of two Greek siblings.</strong>
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<strong>Mannosidosis: two brothers with different degrees of disease severity.</strong>
Clin. Genet. 20: 191-202, 1981.
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[<a href="https://doi.org/10.1111/j.1399-0004.1981.tb01829.x" target="_blank">Full Text</a>]
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<strong>Mannosidosis in an adult.</strong>
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[<a href="https://doi.org/10.1093/hmg/6.5.717" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0140-6736(73)90045-7" target="_blank">Full Text</a>]
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<strong>A generalized storage disorder resembling Hurler's syndrome.</strong>
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<strong>Mannosidosis: isolation of oligosaccharide storage material from brain.</strong>
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[<a href="https://doi.org/10.1016/s0022-3476(69)80259-3" target="_blank">Full Text</a>]
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Poenaru, L., Girard, S., Thepot, F., Madelenat, P., Huraux-Rendu, C., Vinet, M.-C., Dreyfus, J.-C.
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[<a href="https://doi.org/10.1111/j.1399-0004.1979.tb01351.x" target="_blank">Full Text</a>]
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Poenaru, L., Miranda, C., Dreyfus, J.-C.
<strong>Residual mannosidase activity in human mannosidosis: characterization of the mutant enzyme.</strong>
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Riise Stensland, H. M. F., Klenow, H. B., Van Nguyen, L., Hansen, G. M., Malm, D., Nilssen, O.
<strong>Identification of 83 novel alpha-mannosidosis-associated sequence variants: functional analysis of MAN2B1 missense mutations.</strong>
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[<a href="https://doi.org/10.1002/humu.22005" target="_blank">Full Text</a>]
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Roces, D. P., Lullmann-Rauch, R., Peng, J., Balducci, C., Andersson, C., Tollersrud, O., Fogh, J., Orlacchio, A., Beccari, T., Saftig, P., von Figura, K.
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[<a href="https://doi.org/10.1093/hmg/ddh220" target="_blank">Full Text</a>]
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Tollersrud, O. K., Berg, T., Healy, P., Evjen, G., Ramachandran, U., Nilssen, O.
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[<a href="https://doi.org/10.1111/j.1432-1033.1997.00410.x" target="_blank">Full Text</a>]
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<strong>Glycopeptide storage in skin fibroblasts cultured from a patient with alpha-mannosidase deficiency.</strong>
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[<a href="https://doi.org/10.1172/JCI108142" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00692699" target="_blank">Full Text</a>]
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Medicine 56: 335-348, 1977.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/875720/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">875720</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=875720" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1097/00005792-197707000-00005" target="_blank">Full Text</a>]
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Walkley, S. U., Thrall, M. A., Dobrenis, K., Huang, M., March, P. A., Siegel, D. A., Wurzelmann, S.
<strong>Bone marrow transplantation corrects the enzyme defect in neurons of the central nervous system in a lysosomal storage disease.</strong>
Proc. Nat. Acad. Sci. 91: 2970-2974, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8159689/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8159689</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8159689" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.91.8.2970" target="_blank">Full Text</a>]
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Warner, T. G., Mock, A. K., Nyhan, W. L., O'Brien, J. S.
<strong>Alpha-mannosidosis: analysis of urinary oligosaccharides with high performance liquid chromatography and diagnosis of a case with unusually mild presentation.</strong>
Clin. Genet. 25: 248-255, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6705257/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6705257</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6705257" 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.1399-0004.1984.tb01985.x" target="_blank">Full Text</a>]
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<a id="Wiesinger2020" class="mim-anchor"></a>
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Wiesinger, T., Schwarz, M., Mechtler, T. P., Liebmann-Reindl, S., Streubel, B., Kasper, D. C.
<strong>Alpha-mannosidosis--an underdiagnosed lysosomal storage disease in individuals with an 'MPS-like' phenotype.</strong>
Molec. Genet. Metab. 130: 149-152, 2020.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32331969/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32331969</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32331969" 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.2020.04.001" target="_blank">Full Text</a>]
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<a id="Wong1993" class="mim-anchor"></a>
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Wong, L. T. K., Vallance, H., Savage, A., Davidson, A. G. F., Applegarth, D.
<strong>Oral zinc therapy in the treatment of alpha-mannosidosis.</strong>
Am. J. Med. Genet. 46: 410-414, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8357013/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8357013</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8357013" 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.1320460413" target="_blank">Full Text</a>]
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<a id="Yunis1976" class="mim-anchor"></a>
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Yunis, J. J., Lewandowski, R. C., Jr., Sanfilippo, S. J., Tsai, M. Y., Foni, I., Bruhl, H. H.
<strong>Clinical manifestations of mannosidosis--a longitudinal study.</strong>
Am. J. Med. 61: 841-848, 1976.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1008071/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1008071</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1008071" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0002-9343(76)90408-3" target="_blank">Full Text</a>]
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Hilary J. Vernon - updated : 11/12/2024
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Hilary J. Vernon - updated : 05/11/2021<br>Hilary J. Vernon - updated : 11/13/2020<br>Hilary J. Vernon - updated : 05/13/2020<br>Hilary J. Vernon - updated : 04/27/2020<br>Cassandra L. Kniffin - updated : 5/24/2016<br>Cassandra L. Kniffin - updated : 7/17/2012<br>Cassandra L. Kniffin - updated : 5/31/2012<br>Jane Kelly - updated : 8/15/2011<br>Marla J. F. O'Neill - updated : 11/3/2009<br>George E. Tiller - updated : 3/21/2007<br>Cassandra L. Kniffin - reorganized : 7/27/2005<br>Cassandra L. Kniffin - updated : 7/22/2005<br>Victor A. McKusick - updated : 1/7/2000<br>Victor A. McKusick - updated : 2/8/1999<br>Victor A. McKusick - updated : 10/23/1998<br>Victor A. McKusick - updated : 7/7/1998<br>Victor A. McKusick - updated : 12/1/1997<br>Victor A. McKusick - updated : 6/23/1997
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Creation Date:
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Victor A. McKusick : 6/4/1986
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carol : 11/12/2024
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<strong>#</strong> 248500
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MANNOSIDOSIS, ALPHA B, LYSOSOMAL; MANSA
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<em>Alternative titles; symbols</em>
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ALPHA-MANNOSIDOSIS<br />
LYSOSOMAL ALPHA-D-MANNOSIDASE DEFICIENCY<br />
ALPHA-MANNOSIDASE B DEFICIENCY
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<strong>SNOMEDCT:</strong> 124466001, 65524005; &nbsp;
<strong>ORPHA:</strong> 309282, 309288, 61; &nbsp;
<strong>DO:</strong> 3413; &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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19p13.13
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Mannosidosis, alpha-, types I and II
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248500
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Autosomal recessive
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3
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MAN2B1
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609458
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because alpha-mannosidosis (MANSA) is caused by homozygous or compound heterozygous mutation in the MAN2B1 gene (609458) on chromosome 19p13.</p>
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<strong>Description</strong>
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<p>Alpha-mannosidosis (MANSA) is an autosomal recessive lysosomal storage disease characterized by impaired intellectual development, coarse facial features, skeletal abnormalities, hearing impairment, neurologic motor problems, and immune deficiency. Expression of the disease varies considerably, and there is a wide spectrum of clinical findings and severity. Affected children are often normal at birth and during early development. They present in early childhood with delayed psychomotor development, delayed speech, and hearing loss. Additional features include large head with prominent forehead, rounded eyebrows, flattened nasal bridge, macroglossia, widely spaced teeth, dysostosis multiplex, and motor impairment (summary by Malm and Nilssen, 2008). </p><p><strong><em>Classification Systems</em></strong></p><p>
Two classification systems have been used to describe the clinical presentation of alpha-mannosidosis. The earlier system delineated a more severe 'type I,' which shows infantile onset, rapid mental deterioration, hypotonia, splenomegaly, severe dysostosis multiplex, and severe recurrent infections, often resulting in death by age 8 years. Individuals with the less severe 'type II' show normal early development with later childhood development of impaired intellectual development, hearing loss, coarse facies, neurologic deterioration, and survival well into adulthood (summary by Desnick et al., 1976 and Gotoda et al., 1998). A later classification system delineated 3 clinical types. Type 1 is the mildest form, with onset after age 10 years, without skeletal abnormalities and very slow progression. Type 2 is a moderate form, with onset before age 10 years, presence of skeletal abnormalities, and slow progression with development of ataxia by age 20 to 30 years. Type 3 is the severe form, with onset in early infancy, skeletal abnormalities, and obvious progression leading to early death from primary central nervous system involvement or myopathy. Most patients belong to clinical type 2 (summary by Malm and Nilssen, 2008). Despite the clinical heterogeneity of the disorder, there are no apparent genotype/phenotype correlations (Berg et al., 1999; Riise Stensland et al., 2012). </p>
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<strong>Clinical Features</strong>
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<p>Ockerman (1967, 1969) reported a boy with a generalized lysosomal storage disorder resembling Hurler syndrome (607014), but the storage material was not acid mucopolysaccharide. The patient had coarse features, macroglossia, flat nose, large clumsy ears, widely spaced teeth, large head, big hands and feet, tall stature, lenticular opacities, muscular hypotonia, lumbar gibbus, and radiographic skeletal abnormalities. He also had mild hepatosplenomegaly, dilated cerebral ventricles, hypogammaglobulinemia, and susceptibility to infection. Vacuolated lymphocytes were present in the bone marrow and blood. The patient died at age 4.5 years during an episode of increased intracranial pressure. Histologic study showed storage material in the cerebral cortex, brainstem, spinal medulla, neurohypophysis, retina, and myenteric plexus. Total mannose in the liver was strikingly increased. Alpha-mannosidase activity in all tissues studied was abnormally low, whereas other acid hydrolases had higher than normal activities. The term 'mannosidosis' was suggested as the name of the disorder. </p><p>Ockerman et al. (1973) referred to the identification of mannosidosis in 2 Hungarian sisters and 3 Finnish boys, including 2 brothers. A procedure for the study of low molecular weight urinary compounds containing mannose was useful in the study of these cases. </p><p>Bach et al. (1978) reported 2 sibs, born of consanguineous Palestinian parents, with mild mental retardation, delayed speech, coarse facies, and limited mobility of the large joints. Cultured fibroblasts showed partial alpha-mannosidase deficiency (20% of normal), and the sibs were considered to be mildly affected. However, both patients had vacuolated leukocytes and fibroblasts consistent with the disease phenotype. </p><p>In cultured cell from patients with mannosidosis, Desnick et al. (1976) found defects of neutrophil function, including depressed chemotactic responsiveness and impaired phagocytosis of bacteria. They suggested that recurrent respiratory tract infections resulted from immunoglobulin deficiencies. </p><p>Montgomery et al. (1982) found reports of about 50 cases of mannosidosis. Clinical expression varied from few symptoms to death in childhood. Most patients were in their first or second decade of life. Montgomery et al. (1982) described a 32-year-old man who had been diagnosed as having a 'lipochondrodystrophy possibly Hurler syndrome' at the age of 18 months on the basis of hepatosplenomegaly, dysostosis multiplex, and coarse facies. He had a relatively mild and nonprogressive course with deafness, mental retardation, pectus carinatum, thoracolumbar gibbus, thick calvaria, and lens opacities. </p><p>Press et al. (1983) reported a man with mannosidosis who was 33 years old in 1981 when he presented with pancytopenia. He was first seen at age 26 years with massive gingival hypertrophy, severe mental retardation, and bowed femurs. Mannose-laden histiocytes were demonstrated in the gingiva. An autoimmune basis of the pancytopenia was demonstrated by the presence of antiplatelet and antineutrophil antibodies and a low haptoglobin level. The authors speculated that abnormal accumulation of mannose-rich glycoproteins and oligosaccharides in the membranes of blood cells was responsible for the genesis of neoantigenic determinants. </p><p>Michelakakis et al. (1992) described a 13-year-old Greek boy and his 24-year-old sister with type II mannosidosis. Both had mental retardation, sensorineural deafness, and reduced mannosidase levels in plasma and white blood cells. The boy had normal physical and psychomotor development until age 2 when progressive mental regression set in. He also had frequent respiratory infections. He had coarse facial features with thick eyebrows, widely spaced incisors, prognathism, and a low hairline anteriorly. Radiologic survey of the skeleton showed spondylolysis with spondylolisthesis of L5 on S1. The sister had heavy eyebrows and prognathism. </p><p>Bennet et al. (1995) reported 2 unrelated patients with different presentations of mannosidosis. One had onset in early childhood with a severe phenotype characteristic of type I mannosidosis, whereas the other was diagnosed in late adulthood after the onset of progressive neurologic deterioration, consistent with type II mannosidosis. Both were detected by urinary screening of oligosaccharides. Lysosomal alpha-mannosidase activity was markedly reduced in lymphoblasts transformed from both patients' blood cells. Kinetic analyses showed that the enzyme from the type I patient had a 400-fold reduction in affinity, while that from the type II patient was reduced 40-fold. All 4 parents had reduced alpha-mannosidase activity in lymphoblasts. The type I patient had a large hydrocele and bilateral inguinal hernias at birth. Coarse facial appearance and delays in speech development prompted referral at age 13 months. At that time, hepatosplenomegaly and cataracts were noted, together with a broad forehead, frontal bossing, flat occiput, midfacial hypoplasia, epicanthal folds, hypertrichosis, and an anterior hair whorl. Brain scans showed increased ventricular size and macrocephaly. Foamy cytoplasm within vacuolated lymphocytes were demonstrated by bone marrow studies. The woman with type II mannosidosis was said to have a normal phenotype during early childhood, but required special education from the second grade onward. She learned to read and write and was independent until age 25 years when she developed bowel incontinence. Evidence of corticospinal and spinocerebellar tract disease progressed over the ensuing 15 years and was more pronounced in the lower limbs. Cerebrocortical atrophy was first documented at age 35. The diagnosis of mannosidosis was made at the age of 40. </p><p>Gotoda et al. (1998) reported a Japanese woman with alpha-mannosidosis confirmed by genetic analysis (609458.0002). From the age of 1 year she had suffered from recurrent infections, such as bronchitis and otitis media. Hearing loss and delayed psychomotor development were noted at age 2 years. At the age of 9 years she entered a school for the deaf, where she did poorly. She gradually developed gait disturbance. Physical examination at the age of 36 years showed an IQ of 19, coarse facies, retinal degeneration, sensorineural hearing loss, increased deep tendon reflexes, spastic gait, and mild limb ataxia. There were vacuolated lymphocytes in her peripheral blood. Similar vacuoles were also found in biopsied muscle cells and fibroblasts. Lysosomal alpha-mannosidase activity of peripheral leukocytes was decreased to less than 1% of normal controls, whereas other lysosomal enzyme activities were all within the normal range. Thin-layer chromatography showed increased urinary excretion of oligosaccharides. A younger sister, aged 42, had a clinical history and features similar to those of the patient; pathologic examination of muscle from this sister had been reported by Kawai et al. (1985). </p><p>In a patient with alpha-mannosidosis originally reported by Autio et al. (1973), Gotoda et al. (1998) identified compound heterozygosity for 2 mutations in the MAN2B1 gene (609458.0003; 609458.0004). The patient was the only child of healthy, nonconsanguineous parents. He had recurring infections during the first year of life. By age 17 months he was speaking only a few words and impaired hearing was suspected. He had coarse facial features, delayed psychomotor functions, and brisk tendon reflexes. Approximately 80% of his peripheral blood leukocytes were vacuolated, and his alpha-mannosidase activity was reduced to approximately 2% of normal. </p><p>Gutschalk et al. (2004) reported 3 adult sibs, aged 38 to 47 years, with alpha-mannosidosis. In late adolescence, all 3 developed progressive cerebellar ataxia characterized by gait ataxia, impaired smooth pursuit, nystagmus, dysarthria, and extensor plantar responses. All also had sensorineural deafness from early childhood and developed progressive retinal degeneration during late adolescence. One patient reported delusions and hallucinations. MRI showed cerebellar atrophy and periventricular white matter changes. MR spectroscopy showed no evidence of demyelination, and Gutschalk et al. (2004) concluded that the neurodegeneration in adult mannosidosis results from lysosomal accumulation of storage material. </p><p>Courtney and Pennesi (2011) described the ocular findings in 2 brothers with alpha-mannosidosis. In addition to corneal and lenticular changes, the brothers had fundus changes including slightly pale optic discs (mild optic atrophy), retinal vascular attenuation, and mottled retinal pigment epithelium (RPE), most notable in the macula and surrounding the fovea. Additionally, there were numerous nummular yellow-white deposits evident at the level of the RPE. No foveal light reflex, peripapillary sparing, or bone spicule pigmentary change was found in either eye. Spectral-domain optical coherence tomography revealed retinal thinning. Fundus autofluorescence showed granular areas of hypoautofluorescence in the macula as well as in the posterior pole surrounding the optic nerve where speckled hyperautofluorescence was intermixed with hypoautofluorescent areas. </p><p>Lehalle et al. (2019) reported 7 patients, aged 5 to 25 years, from 5 families with MANSA. All 7 patients had biallelic mutations in MAN2B1, reduced leukocyte alpha-mannosidase activity, and elevated mannose-rich oligosaccharides in the urine. All 7 were diagnosed with bilateral hearing loss, either sensorineural or mixed, in the first 8 years of life. Of the 6 patients in whom cognitive features were reported, all had mildly impaired intellectual development or learning disabilities. Skeletal abnormalities were identified in 2 patients: one had dysostosis with thickening of the cranial vault, bilateral coxa vara, irregularity of the glenoidal and acetabular cups and rib thickness, and the other had thickening and modeling anomalies of the long bone metaphyses and irregularity of the vertebral endplates. None of the patients had cognitive regression or early motor delays, and coarsened facial features were only recognized retrospectively in some of the patients. Lehalle et al. (2019) recommended that hearing loss, especially when associated with learning or cognitive abnormalities, should raise a possible diagnosis of alpha-mannosidosis or another lysosomal storage disorder. </p><p><strong><em>Central Nervous System Abnormalities</em></strong></p><p>
Borgwardt et al. (2016) studied central nervous system abnormalities in 34 MANSA patients ranging in age from 6 to 35 years. Ten patients underwent brain MRI and magnetic resonance spectroscopy (MRS). Brain imaging showed occipital white matter signal abnormalities in 5 of the 10 patients, and age-inappropriate myelination in 6. MRS demonstrated significantly elevated mannose complex in gray and white matter, consistent with gliosis. All 34 patients were analyzed for cerebrospinal fluid (CSF) markers: there were elevated concentrations of tau (MAPT; 157140), GFAP (137780), and NEFL (162280) in 97%, 74%, and 41% of CSF samples, respectively. There was a negative correlation between CSF-biomarkers and cognitive function and CSF-oligosaccharides and cognitive function. The data indicated that the disorder is associated with early neuropathologic changes. </p><p>Majovska et al. (2021) reported MRI findings from 13 untreated patients with MANSA. The patients ranged in age from 13 months to 17 years, with a median age of 17 years. A total of 22 MRIs were available; 7 patients had 1 MRI and 6 patients had 2 or more. Focal and/or diffuse hyperintense signals in the cerebral white matter were present in 85% of patients. Cerebellar atrophy was seen in 62%, as early as 5 years of age. Cortical atrophy was seen in 62% and corpus callosum thinning was seen in 23%. Other findings included enlargement of white matter perivascular spaces in 38%, widening of perioptic CSF spaces in 62%, and enlargement of the cisterna magna in 85%. Progression of MRI abnormalities, including progression of cerebral and/or cerebellar atrophy, was observed in 2 of 6 patients who had serial studies. Previously reported findings of hypointensity of the basal ganglia and thalami in patients with MANSA were not identified in this study. The most frequent non-CNS abnormalities were diploic space thickening seen in 100% and mucosal thickening seen in 69%. </p><p>Matlach et al. (2018) reviewed ophthalmologic findings in 32 patients with alpha-mannosidosis. Six patients had strabismus, 2 had cataracts, 2 had corneal gaze, 4 had nystagmus, and 5 had impaired saccades. Fundus abnormalities included optic nerve atrophy in 6 patients (which was partial in 4) and tapetoretinal degeneration with bone spicule formations in 3 patients. Four of 7 patients who were treated with enzyme replacement therapy with velmanase alfa developed retinal degeneration despite ERT treatment. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Diagnosis</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Guffon et al. (2019) proposed diagnostic algorithms for alpha-mannosidosis based on the consensus opinion of an expert panel. They suggested that the most prominent signs that should prompt investigation for this disease in patients 10 years of age and younger include speech delay, hearing loss, developmental delay, and facial dysmorphism. In patients older than 10 years, the most prominent signs include hearing loss, ataxia, psychiatric disturbances, and skeletal abnormalities. Guffon et al. (2019) suggested that enzyme screening in dried blood spot or leukocytes should be the first screening method, followed by confirmatory molecular testing. </p><p>Wiesinger et al. (2020) performed a tandem mass spectrometry enzyme assay for alpha-mannosidosis activity, followed by next-generation sequencing, in 835 dried blood spots from patients with suspected mucopolysaccharidoses (MPS; see, e.g., 607014) but who had negative testing for MPS disorders. They identified 4 patients with alpha-mannosidosis and biallelic mutations in the MAN2B1 gene. Wiesinger et al. (2020) concluded that alpha-mannosidosis should be considered in patients who are being evaluated for MPS disorders. </p><p><strong><em>Prenatal Diagnosis</em></strong></p><p>
Poenaru et al. (1979) reported successful prenatal diagnosis of mannosidosis in 2 at-risk families by analyzing enzyme activity of amniotic cells from the fetus. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Clinical Management</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p><strong><em>Enzyme Replacement Therapy</em></strong></p><p>
Harmatz et al. (2018) reported the effect of enzyme replacement therapy with velmanase alfa in treating alpha-mannosidase across several clinical trials. Using a multiple variable analysis model that takes into account pharmacodynamic, functional, and quality of life domains, Harmatz et al. (2018) showed a clinically meaningful treatment effect and a continued long-term treatment effect. Within the pharmacodynamic domain, it was found that velmanase alfa showed effectiveness in reducing serum oligosaccharide load in most treated patients. There was a greater response to treatment in participants under 18 years of age compared to those greater than 18 years of age. </p><p><strong><em>Negative Reports</em></strong></p><p>
Investigators have demonstrated that zinc can stimulate residual alpha-mannosidase activity in cultured cells from patients with mannosidosis (Kistler et al., 1977). Wong et al. (1993) reported a trial of oral zinc therapy for 3 years in a 4-year-old boy with alpha-mannosidosis. However, after almost 10 years of follow-up of the patient on and off zinc therapy, they concluded that there was no substantial clinical improvement. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Biochemical Features</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Ockerman et al. (1973) found that normal liver alpha-mannosidase exists in at least 3 forms, separable by DEAE cellulose chromatography. The lysosomal A and B forms were most active at pH 4.4, whereas form C was most active at pH 6.0. In 2 cases of mannosidosis, Carroll et al. (1972) found that forms A and B were missing. Cheng et al. (1986) found that although mannosidase A and B differed in their subunit compositions, they were immunologically identical. The authors suggested that the differences in A and B were due to differences in processing, and that both forms arise from a single locus. </p><p>Ben-Yoseph et al. (1982) found that mannosidase activity was normal in the medium of cultured fibroblasts from patients with mannosidosis. However, incubation of the mannosidosis extracellular enzyme with either normal or patient cell lysates resulted in a partial loss of activity, whereas an additive value was observed with the normal extracellular enzyme. Ben-Yoseph et al. (1982) suggested that the enzymatic defect in mannosidosis is expressed only after the enzyme has been delivered to lysosomes and presumably has undergone some form of processing there. However, Cheng et al. (1986) provided evidence that the enzyme secreted by mannosidosis fibroblasts was not related immunologically to lysosomal mannosidase. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Inheritance</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Nilssen et al. (1997) confirmed autosomal recessive inheritance of alpha-mannosidosis in the Palestinian sibs reported by Bach et al. (1978). </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>In 2 Palestinian sibs with alpha-mannosidosis who were originally reported by Bach et al. (1978), Nilssen et al. (1997) identified a homozygous mutation in the MAN2B1 gene (609458.0001). </p><p>In 4 unrelated patients with alpha-mannosidosis, Gotoda et al. (1998) identified homozygous or compound heterozygous mutations in the MAN2B1 gene (609458.0001-609458.0005). </p><p>Riise Stensland et al. (2012) identified 96 different pathogenic mutations in the MAN2B1 gene, including 83 novel mutations, in 130 unrelated patients with alpha-mannosidosis from 30 countries. Most of the mutations were private, but R750W (609458.0004) was found in 50 patients from 16 countries and accounted for 27.3% of disease alleles. Other recurrent mutations included a splice site mutation in intron 14 (609458.0006), found in 13 disease alleles, and L809P (609458.0007), found in 8 disease alleles. Twenty-nine novel missense mutations were identified. Most did not show any residual enzyme activity when expressed in COS-7 cells, but 10 showed some activity, including 5 with 30% or more residual activity. There were no apparent genotype/phenotype correlations. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Population Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Harmatz et al. (2018) stated that the prevalence of alpha-mannosidase is estimated to be as low as 1:1 million live births. </p><p>Riise Stensland et al. (2012) found that the R750W mutation in the MAN2B1 gene (609458.0004) was the most common mutation among 130 unrelated patients with alpha-mannosidosis from 30 countries. It was found in 50 patients from 16 countries and accounted for 27.3% of disease alleles. Haplotype analysis indicated at least 4 independent events causing R750W, with 1 haplotype accounting for 95% of the alleles. Population-based analysis suggested that the mutant allele arose in eastern Europe. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Animal Model</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Hocking et al. (1972) described recessive inheritance of mannosidosis in cattle. The disease is manifest by head tremor, aggressive tendency, ataxia, failure to thrive, and early death. </p><p>Berg et al. (1997) identified a 4-bp deletion in the feline Man2b1 gene in a Persian cat with mannosidosis; the deletion resulted in a frameshift from codon 583 and premature termination at codon 645. No enzyme activity could be detected in the liver of the cat. A domestic long-haired cat expressing a milder phenotype had enzyme activity of 2% of normal; this cat did not possess the 4-bp deletion. </p><p>In the Man2b1 cDNA of alpha-mannosidosis-affected Angus cattle, Tollersrud et al. (1997) found a 961T-C transition, resulting in a phe321-to-leu amino acid substitution. In affected Galloway cattle, they found a 662G-A transition that caused an arg221-to-his substitution. Phe321 and arg221 are conserved among the alpha-mannosidase class-2 family. </p><p>Crawley et al. (1999) identified alpha-mannosidosis in the guinea pig. </p><p><strong><em>Therapeutic Strategies</em></strong></p><p>
Walkley et al. (1994) studied the effects of bone marrow transplantation (BMT) in alpha-mannosidosis in cats where the disease shows clinical, morphologic, and biochemical features closely resembling those in the human disease. BMT-treated animals showed little or no progression of neurologic signs 1 to 2 years after transplant, whereas untreated cats became severely impaired and reached end-stage disease by 6 months of age. Increased lysosomal alpha-mannosidase activity was found in brain tissue of the treated animals, and electron microscopy demonstrated no evidence of lysosomal storage within most neurons. Histochemical localization of acidic alpha-D-mannosidase showed that functional enzyme was present in neurons, glial cells, and cells associated with blood vessels. This study provided direct evidence that bone marrow transplantation can lead to significant replacement of lysosomal hydrolase within neurons of the central nervous system and can compensate for the genetic metabolic defect. </p><p>Roces et al. (2004) reported correction of storage of neutral oligosaccharides in a mouse model of alpha-mannosidosis after intravenous administration of Man2b1 from bovine kidney and human and mouse recombinant MAN2B1. The bovine and human enzymes were barely phosphorylated, whereas the bulk of the mouse Man2b1 contained mannose 6-phosphate recognition markers. Clearance and apparent half-life of the internalized enzyme was dependent on the enzyme source as well as tissue type. The corrective effect was time-, tissue- and dose-dependent, and the effects were observed to be transient. After a single dose injection of MAN2B1, the maximum corrective effect was observed between 2 and 6 days. Injection of 250 microU of human MAN2B1 per gram of body weight followed by a subsequent injection 3.5 days later was sufficient to clear liver, kidney, and heart of neutral oligosaccharides. A decrease in mannose-containing oligosaccharides was also observed in the brain, with storage levels in treated mice less than 30% of levels found in control mice. </p><p>Blanz et al. (2008) demonstrated that the neuropathology of a mouse model for alpha-mannosidosis could be efficiently treated using recombinant human alpha-mannosidase (rhLAMAN). After intravenous administration of various doses (25-500 U/kg), rhLAMAN was widely distributed among tissues, and immunohistochemistry revealed lysosomal delivery of the injected enzyme. Whereas low doses (25 U/kg) led to a greater than 70% clearance of stored substrates in visceral tissues and doses of 250 U/kg were sufficient for clearance in peripheral neurons of the trigeminal ganglion, repeated high-dose injections (500 U/kg) were required to achieve a greater than 50% reduction of brain storage. Successful transfer across the blood-brain barrier was evident as the injected enzyme was found in hippocampal neurons, leading to nearly complete disappearance of storage vacuoles. In addition, the decrease in neuronal storage in the brain correlated with an improvement of the neuromotor disabilities found in untreated alpha-mannosidosis mice. Uptake of rhLAMAN seemed to be independent of mannose-6-phosphate receptors, consistent with the low phosphorylation profile of the enzyme. </p>
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>See Also:</strong>
</span>
</h4>
<span class="mim-text-font">
Arbisser et al. (1976); Autio et al. (1982); Aylsworth et al. (1976);
Gordon et al. (1980); Hultberg (1970); Jolly et al. (1980); Kjellman
et al. (1969); Mali et al. (1976); Mitchell et al. (1981); Poenaru et
al. (1980); Tsay et al. (1975); Vandevelde et al. (1982); Vidgoff et
al. (1977); Warner et al. (1984); Yunis et al. (1976)
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div>
<ol>
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Arbisser, A. I., Murphree, A. L., Garcia, C. A., Howell, R. R.
<strong>Ocular findings in mannosidosis.</strong>
Am. J. Ophthal. 82: 465-471, 1976.
[PubMed: 961797]
[Full Text: https://doi.org/10.1016/0002-9394(76)90496-7]
</p>
</li>
<li>
<p class="mim-text-font">
Autio, S., Louhimo, T., Helenius, M.
<strong>The clinical course of mannosidosis.</strong>
Ann. Clin. Res. 14: 93-97, 1982.
[PubMed: 7149616]
</p>
</li>
<li>
<p class="mim-text-font">
Autio, S., Norden, N. E., Ockerman, P. A., Riekkinen, P., Rapola, J., Louhimo, T.
<strong>Mannosidosis: clinical, fine-structural and biochemical findings in three cases.</strong>
Acta Paediat. Scand. 62: 555-565, 1973.
[PubMed: 4358183]
[Full Text: https://doi.org/10.1111/j.1651-2227.1973.tb17065.x]
</p>
</li>
<li>
<p class="mim-text-font">
Aylsworth, A. S., Taylor, H. A., Stuart, C. M., Thomas, G. H.
<strong>Mannosidosis: phenotype of a severely affected child and characterization of alpha-mannosidase activity in cultured fibroblasts from the patient and his parents.</strong>
J. Pediat. 88: 814-818, 1976.
[PubMed: 5584]
[Full Text: https://doi.org/10.1016/s0022-3476(76)81120-1]
</p>
</li>
<li>
<p class="mim-text-font">
Bach, G., Kohn, G., Lasch, E. E., Massri, M. E., Ornoy, A., Sekeles, E., Legum, C., Cohen, M. M.
<strong>A new variant of mannosidosis with increased residual enzymatic activity and mild clinical manifestation.</strong>
Pediat. Res. 12: 1010-1015, 1978.
[PubMed: 724292]
[Full Text: https://doi.org/10.1203/00006450-197810000-00012]
</p>
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<p class="mim-text-font">
Ben-Yoseph, Y., DeFranco, C. L., Charrow, J., Hahn, L. C., Nadler, H. L.
<strong>Apparently normal extracellular acidic alpha-mannosidase in fibroblast cultures from patients with mannosidosis.</strong>
Am. J. Hum. Genet. 34: 100-111, 1982.
[PubMed: 7081212]
</p>
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<p class="mim-text-font">
Bennet, J. K., Dembure, P. P., Elsas, L. J.
<strong>Clinical and biochemical analysis of two families with type I and type II mannosidosis.</strong>
Am. J. Med. Genet. 55: 21-26, 1995.
[PubMed: 7702090]
[Full Text: https://doi.org/10.1002/ajmg.1320550108]
</p>
</li>
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<p class="mim-text-font">
Berg, T., Riise, H. M. F., Hansen, G. M., Malm, D., Tranebjaerg, L., Tollersrud, O. K., Nilssen, O.
<strong>Spectrum of mutations in alpha-mannosidosis.</strong>
Am. J. Hum. Genet. 64: 77-88, 1999.
[PubMed: 9915946]
[Full Text: https://doi.org/10.1086/302183]
</p>
</li>
<li>
<p class="mim-text-font">
Berg, T., Tollersrud, O. K., Walkley, S. U., Siegel, D., Nilssen, O.
<strong>Purification of feline lysosomal alpha-mannosidase, determination of its cDNA sequence and identification of a mutation causing alpha-mannosidosis in Persian cats.</strong>
Biochem. J. 328: 863-870, 1997.
[PubMed: 9396732]
[Full Text: https://doi.org/10.1042/bj3280863]
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<p class="mim-text-font">
Blanz, J., Stroobants, S., Lullmann-Rauch, R., Morelle, W., Ludemann, M., D'Hooge, R., Reuterwall, H., Michalski, J. C., Fogh, J., Andersson, C., Saftig, P.
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Hum. Molec. Genet. 17: 3437-3445, 2008.
[PubMed: 18713755]
[Full Text: https://doi.org/10.1093/hmg/ddn237]
</p>
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<p class="mim-text-font">
Borgwardt, L., Danielsen, E. R., Thomsen, C., Mansson, J. E., Taouatas, N., Thuesen, A. M., Olsen, K. J., Fogh, J., Dali, C. I., Lund, A. M.
<strong>Alpha-mannosidosis: characterization of CNS pathology and correlation between CNS pathology and cognitive function.</strong>
Clin. Genet. 89: 489-494, 2016.
[PubMed: 26212233]
[Full Text: https://doi.org/10.1111/cge.12642]
</p>
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<li>
<p class="mim-text-font">
Carroll, M., Dance, N., Masson, P. K., Robinson, D., Winchester, B. G.
<strong>Human mannosidosis--the enzymic defect.</strong>
Biochem. Biophys. Res. Commun. 49: 579-583, 1972.
[PubMed: 4640377]
[Full Text: https://doi.org/10.1016/0006-291x(72)90450-0]
</p>
</li>
<li>
<p class="mim-text-font">
Cheng, S. H., Malcolm, S., Pemble, S., Winchester, B.
<strong>Purification and comparison of the structures of human liver acidic alpha-D-mannosidases A and B.</strong>
Biochem. J. 233: 65-72, 1986.
[PubMed: 3954735]
[Full Text: https://doi.org/10.1042/bj2330065]
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Courtney, R. J., Pennesi, M. E.
<strong>Retinal dystrophy in 2 brothers with alpha-mannosidosis.</strong>
Arch. Ophthal. 129: 799-802, 2011.
[PubMed: 21670350]
[Full Text: https://doi.org/10.1001/archophthalmol.2011.134]
</p>
</li>
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<p class="mim-text-font">
Crawley, A. C., Jones, M. Z., Bonning, L. E., Finnie, J. W., Hopwood, J. J.
<strong>Alpha-mannosidosis in the guinea pig: a new animal model for lysosomal storage disorders.</strong>
Pediat. Res. 46: 501-509, 1999.
[PubMed: 10541310]
[Full Text: https://doi.org/10.1203/00006450-199911000-00003]
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Desnick, R. J., Sharp, H. L., Grabowski, G. A., Brunning, R. D., Quie, P. G., Sung, J. H., Gorlin, R. J., Ikonne, J. U.
<strong>Mannosidosis: clinical, morphologic, immunologic, and biochemical studies.</strong>
Pediat. Res. 10: 985-996, 1976.
[PubMed: 995502]
[Full Text: https://doi.org/10.1203/00006450-197612000-00008]
</p>
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<p class="mim-text-font">
Gordon, B. A., Carson, R., Haust, M. D.
<strong>Unusual clinical and ultrastructural features in a boy with biochemically typical mannosidosis.</strong>
Acta Paediat. Scand. 69: 787-792, 1980.
[PubMed: 7211364]
[Full Text: https://doi.org/10.1111/j.1651-2227.1980.tb07154.x]
</p>
</li>
<li>
<p class="mim-text-font">
Gotoda, Y., Wakamatsu, N., Kawai, H., Nishida, Y., Matsumoto, T.
<strong>Missense and nonsense mutations in the lysosomal alpha-mannosidase gene (MANB) in severe and mild forms of alpha-mannosidosis.</strong>
Am. J. Hum. Genet. 63: 1015-1024, 1998.
[PubMed: 9758606]
[Full Text: https://doi.org/10.1086/302048]
</p>
</li>
<li>
<p class="mim-text-font">
Guffon, N., Tylki-Szymanska, A., Borgwardt, L., Lund, A. M., Gil-Campos, M., Parini, R., Hennermann, J. B.
<strong>Recognition of alpha-mannosidosis in paediatric and adult patients: presentation of a diagnostic algorithm from an international working group.</strong>
Molec. Genet. Metab. 126: 470-474, 2019.
[PubMed: 30792122]
[Full Text: https://doi.org/10.1016/j.ymgme.2019.01.024]
</p>
</li>
<li>
<p class="mim-text-font">
Gutschalk, A., Harting, I., Cantz, M., Springer, C., Rohrschneider, K., Meinck, H.-M.
<strong>Adult alpha-mannosidosis: clinical progression in the absence of demyelination.</strong>
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[PubMed: 15534274]
[Full Text: https://doi.org/10.1212/01.wnl.0000143057.25471.4f]
</p>
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<li>
<p class="mim-text-font">
Harmatz, P., Cattaneo, F., Ardigo, D., Geraci, S., Hennermann, J. B., Guffon, N., Lund, A., Hendriksz, C. J. Borgwardt, L.
<strong>Enzyme replacement therapy with velmanase alfa (human recombinant alpha-mannosidase): novel global treatment response model and outcomes in patients with alpha-mannosidosis.</strong>
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[PubMed: 29716835]
[Full Text: https://doi.org/10.1016/j.ymgme.2018.04.003]
</p>
</li>
<li>
<p class="mim-text-font">
Hocking, J. D., Jolly, R. D., Batt, R. D.
<strong>Deficiency of alpha-mannosidase in Angus cattle: an inherited lysosomal storage disease.</strong>
Biochem. J. 128: 69-78, 1972.
[PubMed: 4673577]
[Full Text: https://doi.org/10.1042/bj1280069]
</p>
</li>
<li>
<p class="mim-text-font">
Hultberg, B.
<strong>Properties of alpha-mannosidase in mannosidosis.</strong>
Scand. J. Clin. Lab. Invest. 26: 155-160, 1970.
[PubMed: 5472593]
[Full Text: https://doi.org/10.3109/00365517009049228]
</p>
</li>
<li>
<p class="mim-text-font">
Jolly, R. D., Slack, P. M., Winter, P. J., Murphy, C. E.
<strong>Mannosidosis: patterns of storage and urinary excretion of oligosaccharides in the bovine model.</strong>
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[PubMed: 7436888]
[Full Text: https://doi.org/10.1038/icb.1980.43]
</p>
</li>
<li>
<p class="mim-text-font">
Kawai, H., Nishino, H., Nishida, Y., Yoneda, K., Yoshida, Y., Inui, T., Masuda, K., Saito, S.
<strong>Skeletal muscle pathology of mannosidosis in two siblings with spastic paraplegia.</strong>
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[PubMed: 4082921]
[Full Text: https://doi.org/10.1007/BF00690195]
</p>
</li>
<li>
<p class="mim-text-font">
Kistler, J. P., Lott, I. T., Kolodny, E. H., Friedman, R. B., Nersasian, R., Schnur, J., Mihm, M. C., Dvorak, A. M., Dickersin, R.
<strong>Mannosidosis: new clinical presentation, enzyme studies, and carbohydrate analysis.</strong>
Arch. Neurol. 34: 45-51, 1977.
[PubMed: 12732]
[Full Text: https://doi.org/10.1001/archneur.1977.00500130065013]
</p>
</li>
<li>
<p class="mim-text-font">
Kjellman, B., Gamstorp, I., Brun, A., Ockerman, P. A., Palmgren, B.
<strong>Mannosidosis: a clinical and histopathologic study.</strong>
J. Pediat. 75: 366-373, 1969.
[PubMed: 4979627]
[Full Text: https://doi.org/10.1016/s0022-3476(69)80260-x]
</p>
</li>
<li>
<p class="mim-text-font">
Lehalle, D., Colombo, R., O'Grady, M., Heron, B., Houcinat, N., Kuentz, P., Moutton, S., Sorlin, A., Thevenon, J., Delanne, J., Gay, S., Racine, C., and 11 others.
<strong>Hearing impairment as an early sign of alpha-mannosidosis in children with a mild phenotype: report of seven new cases.</strong>
Am. J. Med. Genet. 179A: 1756-1763, 2019.
[PubMed: 31241255]
[Full Text: https://doi.org/10.1002/ajmg.a.61273]
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Majovska, J., Nestrasil, I., Paulson, A., Nascene, D., Jurickova, K., Hlavata, A., Lund, T., Orchard, P. J., Vaneckova M., Zeman, J., Magner, M., Dusek, P.
<strong>White matter alteration and cerebellar atrophy are hallmarks of brain MRI in alpha-mannosidosis.</strong>
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Mali, J. W. H., Bergers, A. M. G., Van den Hurk, J. J. M. A., Mier, P. D., Van de Staak, W. J. B. M.
<strong>A lysosomal storage disorder of the epidermis characterized by a deficiency of alpha-mannosidase and an accumulation of mannose-rich materials.</strong>
Brit. J. Derm. 95: 627-630, 1976.
[PubMed: 795449]
[Full Text: https://doi.org/10.1111/j.1365-2133.1976.tb07035.x]
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Malm, D., Nilssen, O.
<strong>Alpha-mannosidosis.</strong>
Orphanet J. Rare Dis. 3: 21, 2008. Note: Electronic Article.
[PubMed: 18651971]
[Full Text: https://doi.org/10.1186/1750-1172-3-21]
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Matlach, J., Zindel, T., Amraoui, Y., Arash-Kaps, L., Hennermann, J. B., Pitz, S.
<strong>Retinal and optic nerve degeneration in alpha-mannosidosis.</strong>
Orphanet J. Rare Dis. 13: 88, 2018.
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[Full Text: https://doi.org/10.1186/s13023-018-0829-z]
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Michelakakis, H., Dimitriou, E., Mylona-Karayanni, C., Bartsocas, C. S.
<strong>Phenotypic variability of mannosidosis type II: report of two Greek siblings.</strong>
Genetic Counseling 3: 195-199, 1992.
[PubMed: 1472354]
</p>
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Mitchell, M. L., Erickson, R. P., Schmid, D., Hieber, V., Poznanski, A. K., Hicks, S. P.
<strong>Mannosidosis: two brothers with different degrees of disease severity.</strong>
Clin. Genet. 20: 191-202, 1981.
[PubMed: 7307317]
[Full Text: https://doi.org/10.1111/j.1399-0004.1981.tb01829.x]
</p>
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Montgomery, T. R., Thomas, G. H., Valle, D. L.
<strong>Mannosidosis in an adult.</strong>
Johns Hopkins Med. J. 151: 113-117, 1982.
[PubMed: 7109418]
</p>
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<li>
<p class="mim-text-font">
Nilssen, O., Berg, T., Riise, H. M. F., Ramachandran, U., Evjen, G., Hansen, G. M., Malm, D., Tranebjaerg, L., Tollersrud, O. K.
<strong>Alpha-mannosidosis: functional cloning of the lysosomal alpha-mannosidase cDNA and identification of a mutation in two affected siblings.</strong>
Hum. Molec. Genet. 6: 717-726, 1997.
[PubMed: 9158146]
[Full Text: https://doi.org/10.1093/hmg/6.5.717]
</p>
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Ockerman, P. A., Autio, S., Norder, N. E.
<strong>Diagnosis of mannosidosis.</strong>
Lancet 301: 207-208, 1973. Note: Originally Volume 1.
[PubMed: 4118828]
[Full Text: https://doi.org/10.1016/s0140-6736(73)90045-7]
</p>
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<p class="mim-text-font">
Ockerman, P. A.
<strong>A generalized storage disorder resembling Hurler&#x27;s syndrome.</strong>
Lancet 290: 239-241, 1967. Note: Originally Volume 2.
</p>
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Ockerman, P. A.
<strong>Mannosidosis: isolation of oligosaccharide storage material from brain.</strong>
J. Pediat. 75: 360-365, 1969.
[PubMed: 4979626]
[Full Text: https://doi.org/10.1016/s0022-3476(69)80259-3]
</p>
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Poenaru, L., Girard, S., Thepot, F., Madelenat, P., Huraux-Rendu, C., Vinet, M.-C., Dreyfus, J.-C.
<strong>Antenatal diagnosis in three pregnancies at risk for mannosidosis.</strong>
Clin. Genet. 16: 428-432, 1979.
[PubMed: 393435]
[Full Text: https://doi.org/10.1111/j.1399-0004.1979.tb01351.x]
</p>
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<p class="mim-text-font">
Poenaru, L., Miranda, C., Dreyfus, J.-C.
<strong>Residual mannosidase activity in human mannosidosis: characterization of the mutant enzyme.</strong>
Am. J. Hum. Genet. 32: 354-363, 1980.
[PubMed: 7386463]
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<p class="mim-text-font">
Press, O. W., Fingert, H., Lott, I. T., Dickersin, C. R.
<strong>Pancytopenia in mannosidosis.</strong>
Arch. Intern. Med. 143: 1266-1268, 1983.
[PubMed: 6860058]
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Riise Stensland, H. M. F., Klenow, H. B., Van Nguyen, L., Hansen, G. M., Malm, D., Nilssen, O.
<strong>Identification of 83 novel alpha-mannosidosis-associated sequence variants: functional analysis of MAN2B1 missense mutations.</strong>
Hum. Mutat. 33: 511-520, 2012. Note: Erratum: Hum. Mutat. 37: 827 only, 2016.
[PubMed: 22161967]
[Full Text: https://doi.org/10.1002/humu.22005]
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<li>
<p class="mim-text-font">
Roces, D. P., Lullmann-Rauch, R., Peng, J., Balducci, C., Andersson, C., Tollersrud, O., Fogh, J., Orlacchio, A., Beccari, T., Saftig, P., von Figura, K.
<strong>Efficacy of enzyme replacement therapy in alpha-mannosidosis mice: a preclinical animal study.</strong>
Hum. Molec. Genet. 13: 1979-1988, 2004.
[PubMed: 15269179]
[Full Text: https://doi.org/10.1093/hmg/ddh220]
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Tollersrud, O. K., Berg, T., Healy, P., Evjen, G., Ramachandran, U., Nilssen, O.
<strong>Purification of bovine lysosomal alpha-mannosidase, characterization of its gene and determination of two mutations that cause alpha-mannosidosis.</strong>
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[PubMed: 9208932]
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Tsay, G. C., Dawson, G., Matalon, R.
<strong>Glycopeptide storage in skin fibroblasts cultured from a patient with alpha-mannosidase deficiency.</strong>
J. Clin. Invest. 56: 711-718, 1975.
[PubMed: 125765]
[Full Text: https://doi.org/10.1172/JCI108142]
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Vandevelde, M., Fankhauser, R., Bichsel, P., Wiesmann, U., Herschkowitz, N.
<strong>Hereditary neurovisceral mannosidosis associated with alpha-mannosidase deficiency in a family of Persian cats.</strong>
Acta Neuropath. 58: 64-68, 1982.
[PubMed: 7136518]
[Full Text: https://doi.org/10.1007/BF00692699]
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Vidgoff, J., Lovrien, E. W., Beals, R. K., Buist, N. R. M.
<strong>Mannosidosis in three brothers--a review of the literature.</strong>
Medicine 56: 335-348, 1977.
[PubMed: 875720]
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Walkley, S. U., Thrall, M. A., Dobrenis, K., Huang, M., March, P. A., Siegel, D. A., Wurzelmann, S.
<strong>Bone marrow transplantation corrects the enzyme defect in neurons of the central nervous system in a lysosomal storage disease.</strong>
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[PubMed: 8159689]
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Warner, T. G., Mock, A. K., Nyhan, W. L., O'Brien, J. S.
<strong>Alpha-mannosidosis: analysis of urinary oligosaccharides with high performance liquid chromatography and diagnosis of a case with unusually mild presentation.</strong>
Clin. Genet. 25: 248-255, 1984.
[PubMed: 6705257]
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Wiesinger, T., Schwarz, M., Mechtler, T. P., Liebmann-Reindl, S., Streubel, B., Kasper, D. C.
<strong>Alpha-mannosidosis--an underdiagnosed lysosomal storage disease in individuals with an &#x27;MPS-like&#x27; phenotype.</strong>
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Wong, L. T. K., Vallance, H., Savage, A., Davidson, A. G. F., Applegarth, D.
<strong>Oral zinc therapy in the treatment of alpha-mannosidosis.</strong>
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[PubMed: 8357013]
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</p>
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Yunis, J. J., Lewandowski, R. C., Jr., Sanfilippo, S. J., Tsai, M. Y., Foni, I., Bruhl, H. H.
<strong>Clinical manifestations of mannosidosis--a longitudinal study.</strong>
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[PubMed: 1008071]
[Full Text: https://doi.org/10.1016/0002-9343(76)90408-3]
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Hilary J. Vernon - updated : 11/12/2024<br>Hilary J. Vernon - updated : 05/11/2021<br>Hilary J. Vernon - updated : 11/13/2020<br>Hilary J. Vernon - updated : 05/13/2020<br>Hilary J. Vernon - updated : 04/27/2020<br>Cassandra L. Kniffin - updated : 5/24/2016<br>Cassandra L. Kniffin - updated : 7/17/2012<br>Cassandra L. Kniffin - updated : 5/31/2012<br>Jane Kelly - updated : 8/15/2011<br>Marla J. F. O&#x27;Neill - updated : 11/3/2009<br>George E. Tiller - updated : 3/21/2007<br>Cassandra L. Kniffin - reorganized : 7/27/2005<br>Cassandra L. Kniffin - updated : 7/22/2005<br>Victor A. McKusick - updated : 1/7/2000<br>Victor A. McKusick - updated : 2/8/1999<br>Victor A. McKusick - updated : 10/23/1998<br>Victor A. McKusick - updated : 7/7/1998<br>Victor A. McKusick - updated : 12/1/1997<br>Victor A. McKusick - updated : 6/23/1997
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