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Entry
- #257200 - NIEMANN-PICK DISEASE, TYPE A
- OMIM
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<span class="h4">#257200</span>
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/257200"><strong>Clinical Synopsis</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#pathogenesis">Pathogenesis</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="#clinicalManagement">Clinical Management</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#populationGenetics">Population Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#seeAlso"><strong>See Also</strong></a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=NIEMANN-PICK DISEASE, TYPE A" 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="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=11105&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.acmg.net/PDFLibrary/Niemann-Pick.pdf" class="mim-tip-hint" title="Information and resources for newborn screening and genetics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Newborn Screening', 'domain': 'www.acmg.net'})">Newborn Screening</a></div>
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
<span class="panel-title">
<span class="small">
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Animal Models</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.alliancegenome.org/disease/DOID:0070111" 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/257200" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
<div><a href="https://omia.org/OMIA001795/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
<div><a href="https://wormbase.org/resources/disease/DOID:0070111" 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>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
<span class="panel-title">
<span class="small">
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Cell Lines</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:257200" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
</div>
</div>
</div>
</div>
</div>
</div>
<span>
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
&nbsp;
</span>
</span>
</div>
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>SNOMEDCT:</strong> 52165006<br />
<strong>ICD10CM:</strong> E75.240<br />
<strong>ORPHA:</strong> 77292<br />
<strong>DO:</strong> 0070111<br />
">ICD+</a>
</div>
<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
257200
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
NIEMANN-PICK DISEASE, TYPE A
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<a id="alternativeTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
SPHINGOMYELIN LIPIDOSIS<br />
SPHINGOMYELINASE DEFICIENCY<br />
ACID SPHINGOMYELINASE DEFICIENCY, NEUROVISCERAL TYPE<br />
ASMD, NEUROVISCERAL TYPE
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
<div>
<a id="includedTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
Other entities represented in this entry:
</span>
</p>
</div>
<div>
<span class="h3 mim-font">
NIEMANN-PICK DISEASE, INTERMEDIATE, PROTRACTED NEUROVISCERAL, INCLUDED
</span>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/126?start=-3&limit=10&highlight=126">
11p15.4
</a>
</span>
</td>
<td>
<span class="mim-font">
Niemann-Pick disease, type A
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/257200"> 257200 </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">
SMPD1
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607608"> 607608 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/257200" class="btn btn-warning" role="button"> Clinical Synopsis </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
</button>
</div>
&nbsp;
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
</button>
<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/257200" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/257200" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
</ul>
</div>
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GROWTH </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Height </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Short stature <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422065006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422065006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237836003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237836003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237837007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237837007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E34.31" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E34.31</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R62.52" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R62.52</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.43" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.43</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0349588&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0349588</a>, <a href="https://bioportal.bioontology.org/search?q=C0013336&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013336</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003510</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Weight </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Low body weight <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248342006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248342006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R63.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R63.6</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.22" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.22</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0041667&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0041667</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004325" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004325</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004325" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004325</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Other </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Failure to thrive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/432788009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">432788009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/54840006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">54840006</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0015544&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015544</a>, <a href="https://bioportal.bioontology.org/search?q=C2315100&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2315100</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</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> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Cherry-red maculae (50%) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/49473001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">49473001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0278234&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0278234</a>]</span><br /> -
Gray, granular-appearing maculae <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850374&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850374</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> RESPIRATORY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Frequent respiratory infections <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3806482&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3806482</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002205" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002205</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002205" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002205</a>]</span><br />
</span>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Lung </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Diffuse reticular or finely nodular infiltrations <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843428&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843428</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002207" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002207</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002207" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002207</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ABDOMEN </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> External Features </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Protuberant abdomen <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854928&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854928</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001538" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001538</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001538" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001538</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Liver </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hepatomegaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80515008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80515008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019209&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019209</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span><br /> -
Neonatal jaundice <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/387712008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">387712008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/P59.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">P59.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0022353&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022353</a>, <a href="https://bioportal.bioontology.org/search?q=C1859236&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1859236</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006579" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006579</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006579" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006579</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>
<span class="h5 mim-font">
<em> Gastrointestinal </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Vomiting <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422400008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422400008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/300359004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">300359004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249497008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249497008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R11.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R11.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R11.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R11.10</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042963&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042963</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002013" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002013</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002013" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002013</a>]</span><br /> -
Constipation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/14760008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">14760008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K59.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K59.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K59.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K59.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/564.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">564.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/564.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">564.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0009806&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009806</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002019" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002019</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002019" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002019</a>]</span><br /> -
Feeding difficulties <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/78164000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">78164000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R63.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R63.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0232466&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0232466</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</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">
- Osteoporosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/64859006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">64859006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Z82.62" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Z82.62</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M81.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M81.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/733.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">733.0</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/V17.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">V17.81</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/733.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">733.00</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2911643&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2911643</a>, <a href="https://bioportal.bioontology.org/search?q=C0029456&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029456</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000939" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000939</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000939" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000939</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKIN, NAILS, & HAIR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Skin </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Xanthomas <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/75594004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">75594004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/63103006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">63103006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0302314&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0302314</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001114" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001114</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">
- 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 /> -
Muscle weakness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/26544005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">26544005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151786&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151786</a>, <a href="https://bioportal.bioontology.org/search?q=C0030552&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0030552</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001324" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001324</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001324" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001324</a>]</span><br /> -
Hyporeflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/835279003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">835279003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405946002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405946002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0700078&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700078</a>, <a href="https://bioportal.bioontology.org/search?q=C0151888&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151888</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001265" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001265</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001315" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001315</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001265" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001265</a>]</span><br /> -
Psychomotor retardation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398991009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398991009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1144814003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1144814003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0424230&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424230</a>, <a href="https://bioportal.bioontology.org/search?q=C5441816&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5441816</a>]</span><br /> -
Mental retardation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/228156007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">228156007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/110359009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">110359009</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/317-319.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">317-319.99</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714756&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714756</a>, <a href="https://bioportal.bioontology.org/search?q=C0025362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span><br /> -
Spasticity (later) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850370&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850370</a>]</span> <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">[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 /> -
Rigidity (later) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850371&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850371</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16046003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16046003</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002063" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002063</a>]</span><br /> -
Athetosis (later) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850372&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850372</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/58593005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">58593005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/44913001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">44913001</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002305" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002305</a>]</span><br />
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<span class="h5 mim-font">
<strong> HEMATOLOGY </strong>
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<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Microcytic anemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/234349007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">234349007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5194182&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5194182</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001935" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001935</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001935" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001935</a>]</span><br /> -
Large vacuolated foam cells ('NP cells') on bone marrow biopsy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1856560&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1856560</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004333" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004333</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004333" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004333</a>]</span><br /> -
'Sea blue' histiocytes <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/39474009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">39474009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0333836&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0333836</a>]</span><br />
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<strong> IMMUNOLOGY </strong>
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- Lymphadenopathy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/30746006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">30746006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R59.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R59.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R59" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R59</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R59.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R59.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/785.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">785.6</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4282165&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4282165</a>, <a href="https://bioportal.bioontology.org/search?q=C0497156&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0497156</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002716" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002716</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002716" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002716</a>]</span><br />
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<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
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<span class="mim-font">
- Decreased acid sphingomyelinase activity (less than 5%) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843422&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843422</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0034300" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0034300</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0034300" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0034300</a>]</span><br /> -
Multiple organs (lung, liver, spleen, kidney, brain) contain foamy resident cells and histiocytes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850376&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850376</a>]</span><br /> -
Electron microscopy of foam cells shows lamellar inclusions <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843424&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843424</a>]</span><br />
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<strong> MISCELLANEOUS </strong>
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- Onset in infancy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1848924&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1848924</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003593" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003593</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003593" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003593</a>]</span><br /> -
Death by age 3 years<br /> -
More common in Ashkenazi Jews<br /> -
Allelic disorder to Nieman-Pick disease type B (<a href="/entry/607616">607616</a>)<br />
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<strong> MOLECULAR BASIS </strong>
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- Caused by mutations in the acid lysosomal sphingomyelin phosphodiesterase-1 gene (SMPD1, <a href="/entry/607608#0001">607608.0001</a>)<br />
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<p>A number sign (#) is used with this entry because Niemann-Pick disease type A is caused by homozygous or compound heterozygous mutation in the sphingomyelin phosphodiesterase-1 gene (SMPD1; <a href="/entry/607608">607608</a>), which encodes acid sphingomyelinase (ASM), on chromosome 11p15.</p><p>Niemann-Pick disease type B (<a href="/entry/607616">607616</a>) is an allelic disorder characterized by visceral involvement only and survival into adulthood.</p>
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<strong>Description</strong>
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<p>Niemann-Pick disease types A and B are caused by an inherited deficiency of acid sphingomyelinase activity. The clinical phenotype ranges from a severe infantile form with neurologic degeneration resulting in death usually by 3 years of age (type A) to a later-onset nonneurologic form (type B) that is compatible with survival into adulthood. Since intermediate cases also have been reported, the disease is best regarded as a single entity with a clinical spectrum (summary by <a href="#27" class="mim-tip-reference" title="Schuchman, E. H. &lt;strong&gt;The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease.&lt;/strong&gt; J. Inherit. Metab. Dis. 30: 654-663, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17632693/&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;17632693&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10545-007-0632-9&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17632693">Schuchman, 2007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17632693" 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="Knudson, A. G., Jr., Kaplan, W. D. &lt;strong&gt;Genetics of the sphingolipidoses. In: Aaronson, S. M.; Volk, B. W.: Cerebral Sphingolipidoses. A Symposium on Tay-Sachs Disease.&lt;/strong&gt; New York: Academic Press (pub.) 1962. Pp. 395-411."None>Knudson and Kaplan (1962)</a> suggested that 3 types of the disorder can be distinguished: infantile cerebral, juvenile cerebral, and noncerebral. Later, 5 forms of Niemann-Pick disease were distinguished. Four were delineated by <a href="#5" class="mim-tip-reference" title="Crocker, A. C. &lt;strong&gt;The cerebral defect in Tay-Sachs disease and Niemann-Pick disease.&lt;/strong&gt; J. Neurochem. 7: 69-80, 1961.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/13696518/&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;13696518&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1471-4159.1961.tb13499.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="13696518">Crocker (1961)</a>: the classical infantile form (type A), the visceral form (type B), the subacute or juvenile form (type C; <a href="/entry/257220">257220</a>), and the Nova Scotian variant (type D; see <a href="/entry/257220">257220</a>). The fifth, the adult form (type E; see <a href="/entry/607616">607616</a>), was described by <a href="#30" class="mim-tip-reference" title="Terry, R. D., Sperry, W. M., Brodoff, B. &lt;strong&gt;Adult lipidosis resembling Niemann-Pick&#x27;s disease.&lt;/strong&gt; Am. J. Path. 30: 263-285, 1954.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/13138710/&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;13138710&lt;/a&gt;]" pmid="13138710">Terry et al. (1954)</a> and <a href="#17" class="mim-tip-reference" title="Lynn, R., Terry, R. D. &lt;strong&gt;Lipid histochemistry and electron microscopy in adult Niemann-Pick disease.&lt;/strong&gt; Am. J. Med. 37: 987-994, 1964.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14246098/&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;14246098&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0002-9343(64)90139-1&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="14246098">Lynn and Terry (1964)</a>. <a href="#25" class="mim-tip-reference" title="Schneider, E. L., Pentchev, P. G., Hibbert, S. R., Sawitsky, A., Brady, R. O. &lt;strong&gt;A new form of Niemann-Pick disease characterized by temperature-labile sphingomyelinase.&lt;/strong&gt; J. Med. Genet. 15: 370-374, 1978.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/216805/&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;216805&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.15.5.370&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="216805">Schneider et al. (1978)</a> used the designation type F (see <a href="/entry/607616">607616</a>) for a form characterized in 2 patients by a thermolabile enzyme. Most patients fall into Crocker's group A, with death before age 3 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=13696518+13138710+14246098+216805" 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="#27" class="mim-tip-reference" title="Schuchman, E. H. &lt;strong&gt;The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease.&lt;/strong&gt; J. Inherit. Metab. Dis. 30: 654-663, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17632693/&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;17632693&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10545-007-0632-9&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17632693">Schuchman (2007)</a> provided a detailed review of Niemann-Pick disease type A, including clinical management. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17632693" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In Niemann-Pick disease, lipid, mainly sphingomyelin, accumulates in reticuloendothelial and other cell types throughout the body. The accumulation in ganglion cells of the central nervous system leads to cell death. <a href="#4" class="mim-tip-reference" title="Crocker, A. C., Farber, S. &lt;strong&gt;Niemann-Pick disease: a review of eighteen patients.&lt;/strong&gt; Medicine 37: 1-95, 1958.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/13516139/&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;13516139&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/00005792-195802000-00001&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="13516139">Crocker and Farber (1958)</a> presented a detailed clinical and pathologic account of 18 patients with Niemann-Pick disease. Persistent early jaundice, enlarging abdomen, and poor nutritional and developmental progress were the most common initial complaints. Hepatosplenomegaly, retarded physical and mental growth and severe neurologic disturbances, including hypotonia, rigidity, and mental retardation, were features. Symptoms usually developed by 6 months and death occurred by 3 years of age. <a href="#4" class="mim-tip-reference" title="Crocker, A. C., Farber, S. &lt;strong&gt;Niemann-Pick disease: a review of eighteen patients.&lt;/strong&gt; Medicine 37: 1-95, 1958.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/13516139/&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;13516139&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/00005792-195802000-00001&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="13516139">Crocker and Farber (1958)</a>, <a href="#8" class="mim-tip-reference" title="Forsythe, W. I., McKeown, E. F., Neill, D. W. &lt;strong&gt;Three cases of Niemann-Pick&#x27;s disease in children.&lt;/strong&gt; Arch. Dis. Child. 34: 406-409, 1959.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/13824052/&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;13824052&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/adc.34.177.406&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="13824052">Forsythe et al. (1959)</a>, and others suggested that the biologic behavior can be widely variable. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=13824052+13516139" 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="#36" class="mim-tip-reference" title="Wiedemann, H. R., Gerken, H., Graucob, E., Hansen, H. G. &lt;strong&gt;Recognition of heterozygosity in sphingolipidoses. (Letter)&lt;/strong&gt; Lancet 285: 1283 only, 1965. Note: Originally Volume I."None>Wiedemann et al. (1965)</a> found large storage cells in the bone marrow of both clinically normal parents of a sibship with several affected children. The parents were first cousins. The authors noted that about 40% of cases were Jewish. Heterogeneity was emphasized by <a href="#16" class="mim-tip-reference" title="Lowden, J. A., Laramee, M. A., Wentworth, P. &lt;strong&gt;The subacute form of Niemann-Pick disease.&lt;/strong&gt; Arch. Neurol. 17: 230-237, 1967.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6053566/&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;6053566&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.1967.00470270008002&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="6053566">Lowden et al. (1967)</a> who described non-Jewish sibs with both clinical and chemical differences from the usual disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6053566" 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 addition to a cherry red spot, <a href="#32" class="mim-tip-reference" title="Walton, D. S., Robb, R. M., Crocker, A. C. &lt;strong&gt;Ocular manifestations of group A Niemann-Pick disease.&lt;/strong&gt; Am. J. Ophthal. 85: 174-180, 1978.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/623187/&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;623187&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0002-9394(14)75945-8&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="623187">Walton et al. (1978)</a> found corneal opacification and brown discoloration of the anterior lens capsule in all of 4 infants with type A Niemann-Pick disease who were studied in their first year. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=623187" 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="#1" class="mim-tip-reference" title="Barness, L. A., Wiederhold, S., Chandra, S., Odell, G. B., Shahidi, N. T., Gilbert, E. F. &lt;strong&gt;One-year-old infant with hepatosplenomegaly and developmental delay.&lt;/strong&gt; Am. J. Med. Genet. 28: 411-431, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2447773/&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;2447773&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320280220&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="2447773">Barness et al. (1987)</a> presented a well-studied case of Niemann-Pick disease type A at a clinicopathologic conference. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2447773" 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="McGovern, M. M., Aron, A., Brodie, S. E., Desnick, R. J., Wasserstein, M. P. &lt;strong&gt;Natural history of type A Niemann-Pick disease: possible endpoints for therapeutic trials.&lt;/strong&gt; Neurology 66: 228-232, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16434659/&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;16434659&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.wnl.0000194208.08904.0c&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="16434659">McGovern et al. (2006)</a> reported the natural history of 10 unrelated patients with type A Niemann-Pick disease. All affected infants had a normal neonatal course and early development. The presenting symptom in all patients was hepatosplenomegaly, and the median age at diagnosis was 6 months. Median developmental age for all 10 did not progress beyond 12 months for developmental milestones. None achieved independent sitting, crawling, or walking; most had progressive hypotonia with loss of deep tendon reflexes. All patients had cherry red spots by age 12 months. Nonneurologic symptoms included vomiting, failure to thrive, respiratory infections, irritability, and sleep disturbances. The median time from diagnosis to death was 21 months. <a href="#18" class="mim-tip-reference" title="McGovern, M. M., Aron, A., Brodie, S. E., Desnick, R. J., Wasserstein, M. P. &lt;strong&gt;Natural history of type A Niemann-Pick disease: possible endpoints for therapeutic trials.&lt;/strong&gt; Neurology 66: 228-232, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16434659/&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;16434659&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/01.wnl.0000194208.08904.0c&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="16434659">McGovern et al. (2006)</a> concluded that type A Niemann-Pick disease shows a homogeneous, relentless, neurodegenerative clinical course with death within 3 years of onset. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16434659" 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>Clinical Variability</em></strong></p><p>
<a href="#22" class="mim-tip-reference" title="Pavlu-Pereira, H., Asfaw, B., Poupetova, H., Ledvinova, J., Sikora, J., Vanier, M. T., Sandhoff, K., Zeman, J., Novotna, Z., Chudoba, D., Elleder, M. &lt;strong&gt;Acid sphinogomyelinase deficiency. Phenotype variability with prevalence of intermediate phenotype in a series of twenty-five Czech and Slovak patients. A multi-approach study.&lt;/strong&gt; J. Inherit. Metab. Dis. 28: 203-227, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15877209/&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;15877209&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10545-005-5671-5&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="15877209">Pavlu-Pereira et al. (2005)</a> described 25 Czech and Slovak patients with acid sphingomyelinase deficiency. Five could be clearly classified as having Niemann-Pick disease type A and 4 as having type B. However, 16 (64%) of 25 patients showed variable features, which the authors considered to be an intermediate form of the disease. Twelve of these patients had a combination of visceral storage with a protracted course of neurologic involvement and a general protracted disease course. Three patients had prominent visceral involvement with a rapid course and discrete neuronal storage observed at autopsy. One patient had a rapidly fatal course of visceral involvement without neuronal involvement; he died at age 8 years. The Q292K mutation (<a href="/entry/607608#0015">607608.0015</a>) was strongly associated with a protracted neurovisceral phenotype in 10 of 12 patients. <a href="#22" class="mim-tip-reference" title="Pavlu-Pereira, H., Asfaw, B., Poupetova, H., Ledvinova, J., Sikora, J., Vanier, M. T., Sandhoff, K., Zeman, J., Novotna, Z., Chudoba, D., Elleder, M. &lt;strong&gt;Acid sphinogomyelinase deficiency. Phenotype variability with prevalence of intermediate phenotype in a series of twenty-five Czech and Slovak patients. A multi-approach study.&lt;/strong&gt; J. Inherit. Metab. Dis. 28: 203-227, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15877209/&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;15877209&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s10545-005-5671-5&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="15877209">Pavlu-Pereira et al. (2005)</a> concluded that a phenotypic continuum exists between the basic neurovisceral (type A) and purely visceral (type B) forms of Niemann-Pick disease, and that the intermediate type encompasses a cluster of variants combining clinical features of both types A and B. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15877209" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In the classic infantile type (type A), <a href="#2" class="mim-tip-reference" title="Brady, R. O., Kanfer, J. N., Mock, M. B., Fredrickson, D. S. &lt;strong&gt;The metabolism of sphingomyelin. II. Evidence of an enzymatic deficiency in Niemann-Pick disease.&lt;/strong&gt; Proc. Nat. Acad. Sci. 55: 366-369, 1966.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5220952/&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;5220952&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.55.2.366&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="5220952">Brady et al. (1966)</a> demonstrated that the biochemical defect is deficient activity of the enzyme that catalyzes cleavage of sphingomyelin to phosphorylcholine and ceramide. <a href="#31" class="mim-tip-reference" title="Uhlendorf, B. W., Holtz, A. I., Mock, M. B., Fredrickson, D. S. &lt;strong&gt;Persistence of a metabolic defect in tissue cultures derived from patients with Niemann-Pick disease. In: Aronson, S. M.; Volk, B. W.: Inborn Disorders of Sphingolipid Metabolism.&lt;/strong&gt; Oxford: Pergamon Press (pub.) 1967. Pp. 443-453."None>Uhlendorf et al. (1967)</a> found the metabolic defect in cell culture. Increased sphingomyelin was demonstrated in cells from bone marrow, skin, and amnion; the last makes prenatal diagnosis possible. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5220952" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#26" class="mim-tip-reference" title="Schneider, P. B., Kennedy, E. P. &lt;strong&gt;Sphingomyelinase in normal human spleens and in spleens from subjects with Niemann-Pick disease.&lt;/strong&gt; J. Lipid Res. 8: 202-209, 1967.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4962590/&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;4962590&lt;/a&gt;]" pmid="4962590">Schneider and Kennedy (1967)</a> found that sphingomyelinase is deficient only in the infantile and visceral forms (type B). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4962590" 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="#13" class="mim-tip-reference" title="Kirkegaard, T., Roth, A. G., Petersen, N. H. T., Mahalka, A. K., Olsen, O. D., Moilanen, I., Zylicz, A., Knudsen, J., Sandhoff, K., Arenz, C., Kinnunen, P. K. J., Nylandsted, J., Jaattela, M. &lt;strong&gt;Hsp70 stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal pathology.&lt;/strong&gt; Nature 463: 549-553, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20111001/&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;20111001&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/nature08710&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="20111001">Kirkegaard et al. (2010)</a> showed that Hsp70 (<a href="/entry/140550">140550</a>) stabilizes lysosomes by binding to an endolysosomal anionic phospholipid bis(monoacylglycero)phosphate (BMP), an essential cofactor for lysosomal sphingomyelin metabolism. In acidic environments Hsp70 binds with high affinity and specificity to BMP, thereby facilitating the BMP binding and activity of acid sphingomyelinase (ASM). The inhibition of the Hsp70-BMP interaction by BMP antibodies or a point mutation in Hsp70 (trp90 to phe), as well as the pharmacologic and genetic inhibition of ASM, effectively reverted the Hsp70-mediated stabilization of lysosomes. Notably, the reduced ASM activity in cells from patients with Niemann-Pick disease A and B (<a href="/entry/607616">607616</a>), severe lysosomal storage disorders caused by mutations in the sphingomyelin phosphodiesterase-1 gene (SMPD1; <a href="/entry/607616">607616</a>) encoding ASM, is also associated with a marked decrease in lysosomal stability, and this phenotype could be effectively corrected by treatment with recombinant Hsp70. <a href="#13" class="mim-tip-reference" title="Kirkegaard, T., Roth, A. G., Petersen, N. H. T., Mahalka, A. K., Olsen, O. D., Moilanen, I., Zylicz, A., Knudsen, J., Sandhoff, K., Arenz, C., Kinnunen, P. K. J., Nylandsted, J., Jaattela, M. &lt;strong&gt;Hsp70 stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal pathology.&lt;/strong&gt; Nature 463: 549-553, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20111001/&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;20111001&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/nature08710&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="20111001">Kirkegaard et al. (2010)</a> concluded that, taken together, their data opened exciting possibilities for the development of new treatments for lysosomal storage disorders and cancer with compounds that enter the lysosomal lumen by the endocytic delivery pathway. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20111001" 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>Due to the phenotypic overlap between Gaucher disease (<a href="/entry/230800">230800</a>) and Niemann-Pick disease, <a href="#20" class="mim-tip-reference" title="Oliva, P., Schwarz, M., Mechtler, T. P., Sansen, S., Keutzer, J., Prusa, A. R., Streubel, B., Kasper, D. C. &lt;strong&gt;Importance to include differential diagnostics for acid sphingomyelinase deficiency (ASMD) in patients suspected to have to Gaucher disease.&lt;/strong&gt; Molec. Genet. Metab. 139: 107563, 2023.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/37086570/&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;37086570&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2023.107563&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="37086570">Oliva et al. (2023)</a> investigated the frequency of patients with Niemann-Pick disease in a cohort of 31,838 patients suspected of having Gaucher disease. Blood spot samples in this cohort were tested for both beta-glucocerebrosidase activity and acid sphingomyelinase activity, and those samples with abnormal enzyme activity were then referred for the appropriate gene sequencing. In the cohort of 31,838 patients, 1,171 blood samples had abnormal acid sphingomyelinase activity, and 551 of 1,171 patients had at least 2 SMPD1 mutations. The frequency of patients with Niemann-Pick disease in the suspected Gaucher disease cohort varied based on geographic region, with the highest frequency (1 in 2) in the Middle East and the lowest frequency (1 in 5) Europe. <a href="#20" class="mim-tip-reference" title="Oliva, P., Schwarz, M., Mechtler, T. P., Sansen, S., Keutzer, J., Prusa, A. R., Streubel, B., Kasper, D. C. &lt;strong&gt;Importance to include differential diagnostics for acid sphingomyelinase deficiency (ASMD) in patients suspected to have to Gaucher disease.&lt;/strong&gt; Molec. Genet. Metab. 139: 107563, 2023.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/37086570/&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;37086570&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2023.107563&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="37086570">Oliva et al. (2023)</a> concluded that potentially 1 in 4 patients suspected of having Gaucher disease actually has Niemann-Pick disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=37086570" 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><a href="#33" class="mim-tip-reference" title="Wang, R. Y., Bodamer, O. A., Watson, M. S., Wilcox, W. R. &lt;strong&gt;Lysosomal storage diseases: diagnostic confirmation and management of presymptomatic individuals.&lt;/strong&gt; Genet. Med. 13: 457-484, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21502868/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;21502868&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/GIM.0b013e318211a7e1&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="21502868">Wang et al. (2011)</a> described the ACMG standards and guidelines for the diagnostic confirmation and management of presymptomatic individuals with lysosomal storage diseases. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21502868" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="inheritance" class="mim-anchor"></a>
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<strong>Inheritance</strong>
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<div class="mim-changed mim-change"><p>The transmission pattern of Niemann-Pick disease type A in the Ashkenazi family reported by <a href="#15" class="mim-tip-reference" title="Levran, O., Desnick, R. J., Schuchman, E. H. &lt;strong&gt;Niemann-Pick disease: a frequent missense mutation in the acid sphingomyelinase gene of Ashkenazi Jewish type A and B patients.&lt;/strong&gt; Proc. Nat. Acad. Sci. 88: 3748-3752, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2023926/&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;2023926&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.88.9.3748&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="2023926">Levran et al. (1991)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2023926" 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></div>
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<a id="molecularGenetics" class="mim-anchor"></a>
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<strong>Molecular Genetics</strong>
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<div class="mim-changed mim-change"><p><a href="#15" class="mim-tip-reference" title="Levran, O., Desnick, R. J., Schuchman, E. H. &lt;strong&gt;Niemann-Pick disease: a frequent missense mutation in the acid sphingomyelinase gene of Ashkenazi Jewish type A and B patients.&lt;/strong&gt; Proc. Nat. Acad. Sci. 88: 3748-3752, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2023926/&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;2023926&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.88.9.3748&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="2023926">Levran et al. (1991)</a> identified a homozygous point mutation in the SMPD1 gene (<a href="/entry/607608#0001">607608.0001</a>) in an Ashkenazi Jewish patient with type A Niemann-Pick disease. <a href="#29" class="mim-tip-reference" title="Takahashi, T., Suchi, M., Desnick, R. J., Takada, G., Schuchman, E. H. &lt;strong&gt;Identification and expression of five mutations in the human acid sphingomyelinase gene causing types A and B Niemann-Pick disease: molecular evidence for genetic heterogeneity in the neuronopathic and non-neuronopathic forms.&lt;/strong&gt; J. Biol. Chem. 267: 12552-12558, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1618760/&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;1618760&lt;/a&gt;]" pmid="1618760">Takahashi et al. (1992)</a> characterized 3 SMPD1 mutations (<a href="/entry/607608#0005">607608.0005</a>-<a href="/entry/607608#0007">607608.0007</a>) causing Niemann-Pick disease type A. <a href="#11" class="mim-tip-reference" title="Ida, H., Rennert, O. M., Maekawa, K., Eto, Y. &lt;strong&gt;Identification of three novel mutations in the acid sphingomyelinase gene of Japanese patients with Niemann-Pick disease type A and B.&lt;/strong&gt; Hum. Mutat. 7: 65-67, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8664904/&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;8664904&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(SICI)1098-1004(1996)7:1&lt;65::AID-HUMU10&gt;3.0.CO;2-Q&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8664904">Ida et al. (1996)</a> identified 3 novel mutations in the SMPD1 gene in Japanese patients with type A and type B Niemann-Pick disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2023926+8664904+1618760" 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></div>
<p><a href="#23" class="mim-tip-reference" title="Rodriguez-Pascau, L., Gort, L., Schuchman, E. H., Vilagelui, L., Grinberg, D., Chabas, A. &lt;strong&gt;Identification and characterization of SMPD1 mutations causing Niemann-Pick types A and B in Spanish patients.&lt;/strong&gt; Hum. Mutat. 30: 1117-1122, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19405096/&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;19405096&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=19405096[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.21018&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="19405096">Rodriguez-Pascau et al. (2009)</a> identified 17 different mutations in the SMPD1 gene, including 10 novel mutations (see, e.g., A482E; <a href="/entry/608607#0016">608607.0016</a> and Y467S; <a href="/entry/608607#0017">608607.0017</a>), in 19 Spanish patients and 2 patients from Maghreb in Northern Africa with Niemann-Pick disease type A (8 patients) or type B (13 patients). The most common mutations were R608del (<a href="/entry/607608#0002">607608.0002</a>), found in 38% of alleles, and the A482E mutation, found in 9% of alleles. The R608del mutation was always found in patients with type B disease; the A482E and Y467S mutations were found in type A patients. Functional expression studies of the mutant proteins in COS-7 cells showed decreased enzyme activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19405096" 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="genotypePhenotypeCorrelations" class="mim-anchor"></a>
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<p><a href="#29" class="mim-tip-reference" title="Takahashi, T., Suchi, M., Desnick, R. J., Takada, G., Schuchman, E. H. &lt;strong&gt;Identification and expression of five mutations in the human acid sphingomyelinase gene causing types A and B Niemann-Pick disease: molecular evidence for genetic heterogeneity in the neuronopathic and non-neuronopathic forms.&lt;/strong&gt; J. Biol. Chem. 267: 12552-12558, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1618760/&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;1618760&lt;/a&gt;]" pmid="1618760">Takahashi et al. (1992)</a> concluded that small deletions or nonsense mutations that result in truncated ASM polypeptide and missense mutations that render the enzyme noncatalytic cause type A Niemann-Pick disease, whereas missense mutations that produce a defective enzyme with residual catalytic activity cause a milder nonneuronopathic type B phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1618760" 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>Population Genetics</strong>
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<p>Despite considerable uncertainty about the demographic history of Ashkenazi Jews and their ancestors, <a href="#28" class="mim-tip-reference" title="Slatkin, M. &lt;strong&gt;A population-genetic test of founder effects and implications for Ashkenazi Jewish diseases.&lt;/strong&gt; Am. J. Hum. Genet. 75: 282-293, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15208782/&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;15208782&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=15208782[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/10.1086/423146&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="15208782">Slatkin (2004)</a> considered available genetic data to be consistent with a founder effect resulting from a severe bottleneck in population size between 1100 A.D. and 1400 A.D. and an earlier bottleneck in 75 A.D., at the beginning of the Jewish Diaspora. He concluded that a founder effect can account for the relatively high frequency of alleles causing 4 different lysosomal storage disorders, including Niemann-Pick disease, Tay-Sachs disease (TSD; <a href="/entry/272800">272800</a>), and Gaucher disease (<a href="/entry/230800">230800</a>), if the disease-associated alleles are recessive in their effects on reproductive fitness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15208782" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="animalModel" class="mim-anchor"></a>
<h4 href="#mimAnimalModelFold" id="mimAnimalModelToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>Animal Model</strong>
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<p>By homologous recombination in embryonic stem cells, <a href="#21" class="mim-tip-reference" title="Otterbach, B., Stoffel, W. &lt;strong&gt;Acid sphingomyelinase-deficient mice mimic the neurovisceral form of human lysosomal storage disease (Niemann-Pick disease).&lt;/strong&gt; Cell 81: 1053-1061, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7600574/&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;7600574&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0092-8674(05)80010-8&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="7600574">Otterbach and Stoffel (1995)</a> achieved targeted disruption of the SMPD1 gene in transgenic mice. Homozygous mice accumulated sphingomyelin extensively in the reticuloendothelial system of liver, spleen, bone marrow, and lung, as well as in the brain. Most strikingly, the ganglionic cell layer of Purkinje cells of the cerebellum degenerated completely, leading to severe impairment of neuromotor coordination. The picture resembled that of the neurovisceral form of Niemann-Pick disease (type A). <a href="#10" class="mim-tip-reference" title="Horinouchi, K., Erlich, S., Perl, D. P., Ferlinz, K., Bisgaier, C. L., Sandhoff, K., Desnick, R. J., Stewart, C. L., Schuchman, E. H. &lt;strong&gt;Acid sphingomyelinase deficient mice: a model of types A and B Niemann-Pick disease.&lt;/strong&gt; Nature Genet. 10: 288-293, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7670466/&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;7670466&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng0795-288&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="7670466">Horinouchi et al. (1995)</a> obtained similar results in Asm knockout mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7600574+7670466" 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="seeAlso" class="mim-anchor"></a>
<h4 href="#mimSeeAlsoFold" id="mimSeeAlsoToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimSeeAlsoToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<strong>See Also:</strong>
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<a href="#Brady1966" class="mim-tip-reference" title="Brady, R. O. &lt;strong&gt;The sphingolipidoses.&lt;/strong&gt; New Eng. J. Med. 275: 312-318, 1966.">Brady (1966)</a>; <a href="#Daloze1977" class="mim-tip-reference" title="Daloze, P., Delvin, E. E., Glorieux, F. H., Corman, J. L., Bettez, P., Toussi, T. &lt;strong&gt;Replacement therapy for inherited enzyme deficiency: liver orthotopic transplantation in Niemann-Pick type A.&lt;/strong&gt; Am. J. Med. Genet. 1: 229-239, 1977.">Daloze et al. (1977)</a>; <a href="#Elleder1983" class="mim-tip-reference" title="Elleder, M., Cihula, J. &lt;strong&gt;Niemann-Pick disease (variation in the sphingomyelinase deficient group): neurovisceral phenotype (A) with an abnormally protracted clinical course and variable expression of neurological symptomatology in three siblings.&lt;/strong&gt; Europ. J. Pediat. 140: 323-328, 1983.">Elleder and Cihula (1983)</a>; <a href="#Gal1975" class="mim-tip-reference" title="Gal, A. E., Brady, R. O., Hibbert, S. R., Pentchev, P. G. &lt;strong&gt;A practical chromogenic procedure for the detection of homozygotes and heterozygous carriers of Niemann-Pick disease.&lt;/strong&gt; New Eng. J. Med. 293: 632-636, 1975.">Gal et
al. (1975)</a>; <a href="#Kampine1967" class="mim-tip-reference" title="Kampine, J. P., Brady, R. O., Kanfer, J. N. &lt;strong&gt;Diagnosis of Gaucher&#x27;s disease and Niemann-Pick disease with small samples of venous blood.&lt;/strong&gt; Science 155: 86-88, 1967.">Kampine et al. (1967)</a>; <a href="#Miyawaki1986" class="mim-tip-reference" title="Miyawaki, S., Yoshida, H., Mitsuoka, S., Enomoto, H., Ikehara, S. &lt;strong&gt;A mouse model for Niemann-Pick disease: influence of genetic background on disease expression in spm/spm mice.&lt;/strong&gt; J. Hered. 77: 379-384, 1986.">Miyawaki et al. (1986)</a>; <a href="#Sakiyama1983" class="mim-tip-reference" title="Sakiyama, T., Kitagawa, T., Jhou, H., Miyawaki, S. &lt;strong&gt;Bone marrow transplantation for Niemann-Pick mice.&lt;/strong&gt; J. Inherit. Metab. Dis. 6: 129-130, 1983.">Sakiyama
et al. (1983)</a>; <a href="#Wenger1980" class="mim-tip-reference" title="Wenger, D. A., Sattler, M., Kudoh, T., Snyder, S. P., Kingston, R. S. &lt;strong&gt;Niemann-Pick disease: a genetic model in Siamese cats.&lt;/strong&gt; Science 208: 1471-1473, 1980.">Wenger et al. (1980)</a>; <a href="#Wenger1978" class="mim-tip-reference" title="Wenger, D. A., Wharton, C., Sattler, M., Clark, C. &lt;strong&gt;Niemann-Pick disease: prenatal diagnosis and studies of sphingomyelinase activities.&lt;/strong&gt; Am. J. Med. Genet. 2: 345-356, 1978.">Wenger et al. (1978)</a>
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<a id="references"class="mim-anchor"></a>
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<strong>REFERENCES</strong>
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<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
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<a id="1" class="mim-anchor"></a>
<a id="Barness1987" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Barness, L. A., Wiederhold, S., Chandra, S., Odell, G. B., Shahidi, N. T., Gilbert, E. F.
<strong>One-year-old infant with hepatosplenomegaly and developmental delay.</strong>
Am. J. Med. Genet. 28: 411-431, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2447773/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2447773</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2447773" 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.1320280220" target="_blank">Full Text</a>]
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<a id="2" class="mim-anchor"></a>
<a id="Brady1966" class="mim-anchor"></a>
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<p class="mim-text-font">
Brady, R. O., Kanfer, J. N., Mock, M. B., Fredrickson, D. S.
<strong>The metabolism of sphingomyelin. II. Evidence of an enzymatic deficiency in Niemann-Pick disease.</strong>
Proc. Nat. Acad. Sci. 55: 366-369, 1966.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5220952/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5220952</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5220952" 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.55.2.366" target="_blank">Full Text</a>]
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<a id="3" class="mim-anchor"></a>
<a id="Brady1966" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Brady, R. O.
<strong>The sphingolipidoses.</strong>
New Eng. J. Med. 275: 312-318, 1966.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5940695/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5940695</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5940695" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM196608112750606" target="_blank">Full Text</a>]
</p>
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<a id="4" class="mim-anchor"></a>
<a id="Crocker1958" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Crocker, A. C., Farber, S.
<strong>Niemann-Pick disease: a review of eighteen patients.</strong>
Medicine 37: 1-95, 1958.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13516139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13516139</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13516139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1097/00005792-195802000-00001" target="_blank">Full Text</a>]
</p>
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<a id="5" class="mim-anchor"></a>
<a id="Crocker1961" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Crocker, A. C.
<strong>The cerebral defect in Tay-Sachs disease and Niemann-Pick disease.</strong>
J. Neurochem. 7: 69-80, 1961.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13696518/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13696518</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13696518" 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.1471-4159.1961.tb13499.x" target="_blank">Full Text</a>]
</p>
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<a id="6" class="mim-anchor"></a>
<a id="Daloze1977" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Daloze, P., Delvin, E. E., Glorieux, F. H., Corman, J. L., Bettez, P., Toussi, T.
<strong>Replacement therapy for inherited enzyme deficiency: liver orthotopic transplantation in Niemann-Pick type A.</strong>
Am. J. Med. Genet. 1: 229-239, 1977.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/345809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">345809</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=345809" 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.1320010209" target="_blank">Full Text</a>]
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<a id="7" class="mim-anchor"></a>
<a id="Elleder1983" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Elleder, M., Cihula, J.
<strong>Niemann-Pick disease (variation in the sphingomyelinase deficient group): neurovisceral phenotype (A) with an abnormally protracted clinical course and variable expression of neurological symptomatology in three siblings.</strong>
Europ. J. Pediat. 140: 323-328, 1983.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6628453/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6628453</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6628453" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF00442673" target="_blank">Full Text</a>]
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<a id="8" class="mim-anchor"></a>
<a id="Forsythe1959" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Forsythe, W. I., McKeown, E. F., Neill, D. W.
<strong>Three cases of Niemann-Pick's disease in children.</strong>
Arch. Dis. Child. 34: 406-409, 1959.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13824052/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13824052</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13824052" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/adc.34.177.406" target="_blank">Full Text</a>]
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<a id="Gal1975" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gal, A. E., Brady, R. O., Hibbert, S. R., Pentchev, P. G.
<strong>A practical chromogenic procedure for the detection of homozygotes and heterozygous carriers of Niemann-Pick disease.</strong>
New Eng. J. Med. 293: 632-636, 1975.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/239343/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">239343</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=239343" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM197509252931304" target="_blank">Full Text</a>]
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<a id="10" class="mim-anchor"></a>
<a id="Horinouchi1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Horinouchi, K., Erlich, S., Perl, D. P., Ferlinz, K., Bisgaier, C. L., Sandhoff, K., Desnick, R. J., Stewart, C. L., Schuchman, E. H.
<strong>Acid sphingomyelinase deficient mice: a model of types A and B Niemann-Pick disease.</strong>
Nature Genet. 10: 288-293, 1995.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7670466/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7670466</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7670466" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/ng0795-288" target="_blank">Full Text</a>]
</p>
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<a id="11" class="mim-anchor"></a>
<a id="Ida1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Ida, H., Rennert, O. M., Maekawa, K., Eto, Y.
<strong>Identification of three novel mutations in the acid sphingomyelinase gene of Japanese patients with Niemann-Pick disease type A and B.</strong>
Hum. Mutat. 7: 65-67, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8664904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8664904</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8664904" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/(SICI)1098-1004(1996)7:1&lt;65::AID-HUMU10&gt;3.0.CO;2-Q" target="_blank">Full Text</a>]
</p>
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<a id="12" class="mim-anchor"></a>
<a id="Kampine1967" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kampine, J. P., Brady, R. O., Kanfer, J. N.
<strong>Diagnosis of Gaucher's disease and Niemann-Pick disease with small samples of venous blood.</strong>
Science 155: 86-88, 1967.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6015567/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6015567</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6015567" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1126/science.155.3758.86" target="_blank">Full Text</a>]
</p>
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<a id="13" class="mim-anchor"></a>
<a id="Kirkegaard2010" class="mim-anchor"></a>
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<p class="mim-text-font">
Kirkegaard, T., Roth, A. G., Petersen, N. H. T., Mahalka, A. K., Olsen, O. D., Moilanen, I., Zylicz, A., Knudsen, J., Sandhoff, K., Arenz, C., Kinnunen, P. K. J., Nylandsted, J., Jaattela, M.
<strong>Hsp70 stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal pathology.</strong>
Nature 463: 549-553, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20111001/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20111001</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20111001" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/nature08710" target="_blank">Full Text</a>]
</p>
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<a id="14" class="mim-anchor"></a>
<a id="Knudson1962" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Knudson, A. G., Jr., Kaplan, W. D.
<strong>Genetics of the sphingolipidoses. In: Aaronson, S. M.; Volk, B. W.: Cerebral Sphingolipidoses. A Symposium on Tay-Sachs Disease.</strong>
New York: Academic Press (pub.) 1962. Pp. 395-411.
</p>
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<a id="Levran1991" class="mim-anchor"></a>
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<p class="mim-text-font">
Levran, O., Desnick, R. J., Schuchman, E. H.
<strong>Niemann-Pick disease: a frequent missense mutation in the acid sphingomyelinase gene of Ashkenazi Jewish type A and B patients.</strong>
Proc. Nat. Acad. Sci. 88: 3748-3752, 1991.
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[<a href="https://doi.org/10.1073/pnas.88.9.3748" target="_blank">Full Text</a>]
</p>
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<div class="">
<p class="mim-text-font">
Lowden, J. A., Laramee, M. A., Wentworth, P.
<strong>The subacute form of Niemann-Pick disease.</strong>
Arch. Neurol. 17: 230-237, 1967.
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[<a href="https://doi.org/10.1001/archneur.1967.00470270008002" target="_blank">Full Text</a>]
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<div class="">
<p class="mim-text-font">
Lynn, R., Terry, R. D.
<strong>Lipid histochemistry and electron microscopy in adult Niemann-Pick disease.</strong>
Am. J. Med. 37: 987-994, 1964.
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[<a href="https://doi.org/10.1016/0002-9343(64)90139-1" target="_blank">Full Text</a>]
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<a id="McGovern2006" class="mim-anchor"></a>
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McGovern, M. M., Aron, A., Brodie, S. E., Desnick, R. J., Wasserstein, M. P.
<strong>Natural history of type A Niemann-Pick disease: possible endpoints for therapeutic trials.</strong>
Neurology 66: 228-232, 2006.
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[<a href="https://doi.org/10.1212/01.wnl.0000194208.08904.0c" target="_blank">Full Text</a>]
</p>
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<a id="19" class="mim-anchor"></a>
<a id="Miyawaki1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Miyawaki, S., Yoshida, H., Mitsuoka, S., Enomoto, H., Ikehara, S.
<strong>A mouse model for Niemann-Pick disease: influence of genetic background on disease expression in spm/spm mice.</strong>
J. Hered. 77: 379-384, 1986.
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[<a href="https://doi.org/10.1093/oxfordjournals.jhered.a110265" target="_blank">Full Text</a>]
</p>
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<a id="20" class="mim-anchor"></a>
<a id="Oliva2023" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Oliva, P., Schwarz, M., Mechtler, T. P., Sansen, S., Keutzer, J., Prusa, A. R., Streubel, B., Kasper, D. C.
<strong>Importance to include differential diagnostics for acid sphingomyelinase deficiency (ASMD) in patients suspected to have to Gaucher disease.</strong>
Molec. Genet. Metab. 139: 107563, 2023.
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[<a href="https://doi.org/10.1016/j.ymgme.2023.107563" target="_blank">Full Text</a>]
</p>
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<a id="21" class="mim-anchor"></a>
<a id="Otterbach1995" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Otterbach, B., Stoffel, W.
<strong>Acid sphingomyelinase-deficient mice mimic the neurovisceral form of human lysosomal storage disease (Niemann-Pick disease).</strong>
Cell 81: 1053-1061, 1995.
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[<a href="https://doi.org/10.1016/s0092-8674(05)80010-8" target="_blank">Full Text</a>]
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<a id="22" class="mim-anchor"></a>
<a id="Pavlu-Pereira2005" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Pavlu-Pereira, H., Asfaw, B., Poupetova, H., Ledvinova, J., Sikora, J., Vanier, M. T., Sandhoff, K., Zeman, J., Novotna, Z., Chudoba, D., Elleder, M.
<strong>Acid sphinogomyelinase deficiency. Phenotype variability with prevalence of intermediate phenotype in a series of twenty-five Czech and Slovak patients. A multi-approach study.</strong>
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[<a href="https://doi.org/10.1007/s10545-005-5671-5" target="_blank">Full Text</a>]
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<a id="23" class="mim-anchor"></a>
<a id="Rodriguez-Pascau2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Rodriguez-Pascau, L., Gort, L., Schuchman, E. H., Vilagelui, L., Grinberg, D., Chabas, A.
<strong>Identification and characterization of SMPD1 mutations causing Niemann-Pick types A and B in Spanish patients.</strong>
Hum. Mutat. 30: 1117-1122, 2009.
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[<a href="https://doi.org/10.1002/humu.21018" target="_blank">Full Text</a>]
</p>
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<a id="24" class="mim-anchor"></a>
<a id="Sakiyama1983" class="mim-anchor"></a>
<div class="">
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Sakiyama, T., Kitagawa, T., Jhou, H., Miyawaki, S.
<strong>Bone marrow transplantation for Niemann-Pick mice.</strong>
J. Inherit. Metab. Dis. 6: 129-130, 1983.
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[<a href="https://doi.org/10.1007/BF01800746" target="_blank">Full Text</a>]
</p>
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<a id="Schneider1978" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Schneider, E. L., Pentchev, P. G., Hibbert, S. R., Sawitsky, A., Brady, R. O.
<strong>A new form of Niemann-Pick disease characterized by temperature-labile sphingomyelinase.</strong>
J. Med. Genet. 15: 370-374, 1978.
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[<a href="https://doi.org/10.1136/jmg.15.5.370" target="_blank">Full Text</a>]
</p>
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<a id="Schneider1967" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Schneider, P. B., Kennedy, E. P.
<strong>Sphingomyelinase in normal human spleens and in spleens from subjects with Niemann-Pick disease.</strong>
J. Lipid Res. 8: 202-209, 1967.
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<a id="Schuchman2007" class="mim-anchor"></a>
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<p class="mim-text-font">
Schuchman, E. H.
<strong>The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease.</strong>
J. Inherit. Metab. Dis. 30: 654-663, 2007.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17632693/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17632693</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17632693" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/s10545-007-0632-9" target="_blank">Full Text</a>]
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Slatkin, M.
<strong>A population-genetic test of founder effects and implications for Ashkenazi Jewish diseases.</strong>
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[<a href="https://doi.org/10.1086/423146" target="_blank">Full Text</a>]
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<a id="Takahashi1992" class="mim-anchor"></a>
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<p class="mim-text-font">
Takahashi, T., Suchi, M., Desnick, R. J., Takada, G., Schuchman, E. H.
<strong>Identification and expression of five mutations in the human acid sphingomyelinase gene causing types A and B Niemann-Pick disease: molecular evidence for genetic heterogeneity in the neuronopathic and non-neuronopathic forms.</strong>
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<div class="">
<p class="mim-text-font">
Terry, R. D., Sperry, W. M., Brodoff, B.
<strong>Adult lipidosis resembling Niemann-Pick's disease.</strong>
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<a id="Uhlendorf1967" class="mim-anchor"></a>
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Uhlendorf, B. W., Holtz, A. I., Mock, M. B., Fredrickson, D. S.
<strong>Persistence of a metabolic defect in tissue cultures derived from patients with Niemann-Pick disease. In: Aronson, S. M.; Volk, B. W.: Inborn Disorders of Sphingolipid Metabolism.</strong>
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Walton, D. S., Robb, R. M., Crocker, A. C.
<strong>Ocular manifestations of group A Niemann-Pick disease.</strong>
Am. J. Ophthal. 85: 174-180, 1978.
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[<a href="https://doi.org/10.1016/s0002-9394(14)75945-8" target="_blank">Full Text</a>]
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<a id="Wang2011" class="mim-anchor"></a>
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<p class="mim-text-font">
Wang, R. Y., Bodamer, O. A., Watson, M. S., Wilcox, W. R.
<strong>Lysosomal storage diseases: diagnostic confirmation and management of presymptomatic individuals.</strong>
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[<a href="https://doi.org/10.1097/GIM.0b013e318211a7e1" target="_blank">Full Text</a>]
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<a id="Wenger1980" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wenger, D. A., Sattler, M., Kudoh, T., Snyder, S. P., Kingston, R. S.
<strong>Niemann-Pick disease: a genetic model in Siamese cats.</strong>
Science 208: 1471-1473, 1980.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7189903/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7189903</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7189903" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1126/science.7189903" target="_blank">Full Text</a>]
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<a id="Wenger1978" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wenger, D. A., Wharton, C., Sattler, M., Clark, C.
<strong>Niemann-Pick disease: prenatal diagnosis and studies of sphingomyelinase activities.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/233699/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">233699</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=233699" 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.1320020405" target="_blank">Full Text</a>]
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<a id="Wiedemann1965" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wiedemann, H. R., Gerken, H., Graucob, E., Hansen, H. G.
<strong>Recognition of heterozygosity in sphingolipidoses. (Letter)</strong>
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Hilary J. Vernon - updated : 05/25/2023
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Ada Hamosh - updated : 10/04/2012<br>Cassandra L. Kniffin - updated : 11/11/2009<br>Cassandra L. Kniffin - updated : 1/7/2009<br>Cassandra L. Kniffin - updated : 4/10/2006<br>Victor A. McKusick - updated : 8/17/2004<br>Cassandra L. Kniffin - reorganized : 3/13/2003<br>Victor A. McKusick - updated : 1/8/2003<br>Victor A. McKusick - updated : 4/29/2002<br>George E. Tiller - updated : 10/25/2000<br>Stylianos E. Antonarakis - updated : 1/16/1998
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Victor A. McKusick : 6/4/1986
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<h3>
<span class="mim-font">
<strong>#</strong> 257200
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<span class="mim-font">
NIEMANN-PICK DISEASE, TYPE A
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<span class="mim-font">
<em>Alternative titles; symbols</em>
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SPHINGOMYELIN LIPIDOSIS<br />
SPHINGOMYELINASE DEFICIENCY<br />
ACID SPHINGOMYELINASE DEFICIENCY, NEUROVISCERAL TYPE<br />
ASMD, NEUROVISCERAL TYPE
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Other entities represented in this entry:
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NIEMANN-PICK DISEASE, INTERMEDIATE, PROTRACTED NEUROVISCERAL, INCLUDED
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<strong>SNOMEDCT:</strong> 52165006; &nbsp;
<strong>ICD10CM:</strong> E75.240; &nbsp;
<strong>ORPHA:</strong> 77292; &nbsp;
<strong>DO:</strong> 0070111; &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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<span class="mim-font">
11p15.4
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Niemann-Pick disease, type A
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257200
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Autosomal recessive
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3
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SMPD1
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607608
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because Niemann-Pick disease type A is caused by homozygous or compound heterozygous mutation in the sphingomyelin phosphodiesterase-1 gene (SMPD1; 607608), which encodes acid sphingomyelinase (ASM), on chromosome 11p15.</p><p>Niemann-Pick disease type B (607616) is an allelic disorder characterized by visceral involvement only and survival into adulthood.</p>
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<strong>Description</strong>
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<p>Niemann-Pick disease types A and B are caused by an inherited deficiency of acid sphingomyelinase activity. The clinical phenotype ranges from a severe infantile form with neurologic degeneration resulting in death usually by 3 years of age (type A) to a later-onset nonneurologic form (type B) that is compatible with survival into adulthood. Since intermediate cases also have been reported, the disease is best regarded as a single entity with a clinical spectrum (summary by Schuchman, 2007). </p><p>Knudson and Kaplan (1962) suggested that 3 types of the disorder can be distinguished: infantile cerebral, juvenile cerebral, and noncerebral. Later, 5 forms of Niemann-Pick disease were distinguished. Four were delineated by Crocker (1961): the classical infantile form (type A), the visceral form (type B), the subacute or juvenile form (type C; 257220), and the Nova Scotian variant (type D; see 257220). The fifth, the adult form (type E; see 607616), was described by Terry et al. (1954) and Lynn and Terry (1964). Schneider et al. (1978) used the designation type F (see 607616) for a form characterized in 2 patients by a thermolabile enzyme. Most patients fall into Crocker's group A, with death before age 3 years. </p><p>Schuchman (2007) provided a detailed review of Niemann-Pick disease type A, including clinical management. </p>
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<strong>Clinical Features</strong>
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<p>In Niemann-Pick disease, lipid, mainly sphingomyelin, accumulates in reticuloendothelial and other cell types throughout the body. The accumulation in ganglion cells of the central nervous system leads to cell death. Crocker and Farber (1958) presented a detailed clinical and pathologic account of 18 patients with Niemann-Pick disease. Persistent early jaundice, enlarging abdomen, and poor nutritional and developmental progress were the most common initial complaints. Hepatosplenomegaly, retarded physical and mental growth and severe neurologic disturbances, including hypotonia, rigidity, and mental retardation, were features. Symptoms usually developed by 6 months and death occurred by 3 years of age. Crocker and Farber (1958), Forsythe et al. (1959), and others suggested that the biologic behavior can be widely variable. </p><p>Wiedemann et al. (1965) found large storage cells in the bone marrow of both clinically normal parents of a sibship with several affected children. The parents were first cousins. The authors noted that about 40% of cases were Jewish. Heterogeneity was emphasized by Lowden et al. (1967) who described non-Jewish sibs with both clinical and chemical differences from the usual disease. </p><p>In addition to a cherry red spot, Walton et al. (1978) found corneal opacification and brown discoloration of the anterior lens capsule in all of 4 infants with type A Niemann-Pick disease who were studied in their first year. </p><p>Barness et al. (1987) presented a well-studied case of Niemann-Pick disease type A at a clinicopathologic conference. </p><p>McGovern et al. (2006) reported the natural history of 10 unrelated patients with type A Niemann-Pick disease. All affected infants had a normal neonatal course and early development. The presenting symptom in all patients was hepatosplenomegaly, and the median age at diagnosis was 6 months. Median developmental age for all 10 did not progress beyond 12 months for developmental milestones. None achieved independent sitting, crawling, or walking; most had progressive hypotonia with loss of deep tendon reflexes. All patients had cherry red spots by age 12 months. Nonneurologic symptoms included vomiting, failure to thrive, respiratory infections, irritability, and sleep disturbances. The median time from diagnosis to death was 21 months. McGovern et al. (2006) concluded that type A Niemann-Pick disease shows a homogeneous, relentless, neurodegenerative clinical course with death within 3 years of onset. </p><p><strong><em>Clinical Variability</em></strong></p><p>
Pavlu-Pereira et al. (2005) described 25 Czech and Slovak patients with acid sphingomyelinase deficiency. Five could be clearly classified as having Niemann-Pick disease type A and 4 as having type B. However, 16 (64%) of 25 patients showed variable features, which the authors considered to be an intermediate form of the disease. Twelve of these patients had a combination of visceral storage with a protracted course of neurologic involvement and a general protracted disease course. Three patients had prominent visceral involvement with a rapid course and discrete neuronal storage observed at autopsy. One patient had a rapidly fatal course of visceral involvement without neuronal involvement; he died at age 8 years. The Q292K mutation (607608.0015) was strongly associated with a protracted neurovisceral phenotype in 10 of 12 patients. Pavlu-Pereira et al. (2005) concluded that a phenotypic continuum exists between the basic neurovisceral (type A) and purely visceral (type B) forms of Niemann-Pick disease, and that the intermediate type encompasses a cluster of variants combining clinical features of both types A and B. </p>
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<strong>Pathogenesis</strong>
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<p>In the classic infantile type (type A), Brady et al. (1966) demonstrated that the biochemical defect is deficient activity of the enzyme that catalyzes cleavage of sphingomyelin to phosphorylcholine and ceramide. Uhlendorf et al. (1967) found the metabolic defect in cell culture. Increased sphingomyelin was demonstrated in cells from bone marrow, skin, and amnion; the last makes prenatal diagnosis possible. </p><p>Schneider and Kennedy (1967) found that sphingomyelinase is deficient only in the infantile and visceral forms (type B). </p>
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<strong>Biochemical Features</strong>
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<p>Kirkegaard et al. (2010) showed that Hsp70 (140550) stabilizes lysosomes by binding to an endolysosomal anionic phospholipid bis(monoacylglycero)phosphate (BMP), an essential cofactor for lysosomal sphingomyelin metabolism. In acidic environments Hsp70 binds with high affinity and specificity to BMP, thereby facilitating the BMP binding and activity of acid sphingomyelinase (ASM). The inhibition of the Hsp70-BMP interaction by BMP antibodies or a point mutation in Hsp70 (trp90 to phe), as well as the pharmacologic and genetic inhibition of ASM, effectively reverted the Hsp70-mediated stabilization of lysosomes. Notably, the reduced ASM activity in cells from patients with Niemann-Pick disease A and B (607616), severe lysosomal storage disorders caused by mutations in the sphingomyelin phosphodiesterase-1 gene (SMPD1; 607616) encoding ASM, is also associated with a marked decrease in lysosomal stability, and this phenotype could be effectively corrected by treatment with recombinant Hsp70. Kirkegaard et al. (2010) concluded that, taken together, their data opened exciting possibilities for the development of new treatments for lysosomal storage disorders and cancer with compounds that enter the lysosomal lumen by the endocytic delivery pathway. </p><p>Due to the phenotypic overlap between Gaucher disease (230800) and Niemann-Pick disease, Oliva et al. (2023) investigated the frequency of patients with Niemann-Pick disease in a cohort of 31,838 patients suspected of having Gaucher disease. Blood spot samples in this cohort were tested for both beta-glucocerebrosidase activity and acid sphingomyelinase activity, and those samples with abnormal enzyme activity were then referred for the appropriate gene sequencing. In the cohort of 31,838 patients, 1,171 blood samples had abnormal acid sphingomyelinase activity, and 551 of 1,171 patients had at least 2 SMPD1 mutations. The frequency of patients with Niemann-Pick disease in the suspected Gaucher disease cohort varied based on geographic region, with the highest frequency (1 in 2) in the Middle East and the lowest frequency (1 in 5) Europe. Oliva et al. (2023) concluded that potentially 1 in 4 patients suspected of having Gaucher disease actually has Niemann-Pick disease. </p>
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<strong>Clinical Management</strong>
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<p>Wang et al. (2011) described the ACMG standards and guidelines for the diagnostic confirmation and management of presymptomatic individuals with lysosomal storage diseases. </p>
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<strong>Inheritance</strong>
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<p>The transmission pattern of Niemann-Pick disease type A in the Ashkenazi family reported by Levran et al. (1991) was consistent with autosomal recessive inheritance. </p>
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<span class="mim-font">
<strong>Molecular Genetics</strong>
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<p>Levran et al. (1991) identified a homozygous point mutation in the SMPD1 gene (607608.0001) in an Ashkenazi Jewish patient with type A Niemann-Pick disease. Takahashi et al. (1992) characterized 3 SMPD1 mutations (607608.0005-607608.0007) causing Niemann-Pick disease type A. Ida et al. (1996) identified 3 novel mutations in the SMPD1 gene in Japanese patients with type A and type B Niemann-Pick disease. </p><p>Rodriguez-Pascau et al. (2009) identified 17 different mutations in the SMPD1 gene, including 10 novel mutations (see, e.g., A482E; 608607.0016 and Y467S; 608607.0017), in 19 Spanish patients and 2 patients from Maghreb in Northern Africa with Niemann-Pick disease type A (8 patients) or type B (13 patients). The most common mutations were R608del (607608.0002), found in 38% of alleles, and the A482E mutation, found in 9% of alleles. The R608del mutation was always found in patients with type B disease; the A482E and Y467S mutations were found in type A patients. Functional expression studies of the mutant proteins in COS-7 cells showed decreased enzyme activity. </p>
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<strong>Genotype/Phenotype Correlations</strong>
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<p>Takahashi et al. (1992) concluded that small deletions or nonsense mutations that result in truncated ASM polypeptide and missense mutations that render the enzyme noncatalytic cause type A Niemann-Pick disease, whereas missense mutations that produce a defective enzyme with residual catalytic activity cause a milder nonneuronopathic type B phenotype. </p>
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<strong>Population Genetics</strong>
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<p>Despite considerable uncertainty about the demographic history of Ashkenazi Jews and their ancestors, Slatkin (2004) considered available genetic data to be consistent with a founder effect resulting from a severe bottleneck in population size between 1100 A.D. and 1400 A.D. and an earlier bottleneck in 75 A.D., at the beginning of the Jewish Diaspora. He concluded that a founder effect can account for the relatively high frequency of alleles causing 4 different lysosomal storage disorders, including Niemann-Pick disease, Tay-Sachs disease (TSD; 272800), and Gaucher disease (230800), if the disease-associated alleles are recessive in their effects on reproductive fitness. </p>
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<strong>Animal Model</strong>
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<p>By homologous recombination in embryonic stem cells, Otterbach and Stoffel (1995) achieved targeted disruption of the SMPD1 gene in transgenic mice. Homozygous mice accumulated sphingomyelin extensively in the reticuloendothelial system of liver, spleen, bone marrow, and lung, as well as in the brain. Most strikingly, the ganglionic cell layer of Purkinje cells of the cerebellum degenerated completely, leading to severe impairment of neuromotor coordination. The picture resembled that of the neurovisceral form of Niemann-Pick disease (type A). Horinouchi et al. (1995) obtained similar results in Asm knockout mice. </p>
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<span class="mim-font">
<strong>See Also:</strong>
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Brady (1966); Daloze et al. (1977); Elleder and Cihula (1983); Gal et
al. (1975); Kampine et al. (1967); Miyawaki et al. (1986); Sakiyama
et al. (1983); Wenger et al. (1980); Wenger et al. (1978)
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<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
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<ol>
<li>
<p class="mim-text-font">
Barness, L. A., Wiederhold, S., Chandra, S., Odell, G. B., Shahidi, N. T., Gilbert, E. F.
<strong>One-year-old infant with hepatosplenomegaly and developmental delay.</strong>
Am. J. Med. Genet. 28: 411-431, 1987.
[PubMed: 2447773]
[Full Text: https://doi.org/10.1002/ajmg.1320280220]
</p>
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<li>
<p class="mim-text-font">
Brady, R. O., Kanfer, J. N., Mock, M. B., Fredrickson, D. S.
<strong>The metabolism of sphingomyelin. II. Evidence of an enzymatic deficiency in Niemann-Pick disease.</strong>
Proc. Nat. Acad. Sci. 55: 366-369, 1966.
[PubMed: 5220952]
[Full Text: https://doi.org/10.1073/pnas.55.2.366]
</p>
</li>
<li>
<p class="mim-text-font">
Brady, R. O.
<strong>The sphingolipidoses.</strong>
New Eng. J. Med. 275: 312-318, 1966.
[PubMed: 5940695]
[Full Text: https://doi.org/10.1056/NEJM196608112750606]
</p>
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<li>
<p class="mim-text-font">
Crocker, A. C., Farber, S.
<strong>Niemann-Pick disease: a review of eighteen patients.</strong>
Medicine 37: 1-95, 1958.
[PubMed: 13516139]
[Full Text: https://doi.org/10.1097/00005792-195802000-00001]
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<li>
<p class="mim-text-font">
Crocker, A. C.
<strong>The cerebral defect in Tay-Sachs disease and Niemann-Pick disease.</strong>
J. Neurochem. 7: 69-80, 1961.
[PubMed: 13696518]
[Full Text: https://doi.org/10.1111/j.1471-4159.1961.tb13499.x]
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<li>
<p class="mim-text-font">
Daloze, P., Delvin, E. E., Glorieux, F. H., Corman, J. L., Bettez, P., Toussi, T.
<strong>Replacement therapy for inherited enzyme deficiency: liver orthotopic transplantation in Niemann-Pick type A.</strong>
Am. J. Med. Genet. 1: 229-239, 1977.
[PubMed: 345809]
[Full Text: https://doi.org/10.1002/ajmg.1320010209]
</p>
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<li>
<p class="mim-text-font">
Elleder, M., Cihula, J.
<strong>Niemann-Pick disease (variation in the sphingomyelinase deficient group): neurovisceral phenotype (A) with an abnormally protracted clinical course and variable expression of neurological symptomatology in three siblings.</strong>
Europ. J. Pediat. 140: 323-328, 1983.
[PubMed: 6628453]
[Full Text: https://doi.org/10.1007/BF00442673]
</p>
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<li>
<p class="mim-text-font">
Forsythe, W. I., McKeown, E. F., Neill, D. W.
<strong>Three cases of Niemann-Pick&#x27;s disease in children.</strong>
Arch. Dis. Child. 34: 406-409, 1959.
[PubMed: 13824052]
[Full Text: https://doi.org/10.1136/adc.34.177.406]
</p>
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<li>
<p class="mim-text-font">
Gal, A. E., Brady, R. O., Hibbert, S. R., Pentchev, P. G.
<strong>A practical chromogenic procedure for the detection of homozygotes and heterozygous carriers of Niemann-Pick disease.</strong>
New Eng. J. Med. 293: 632-636, 1975.
[PubMed: 239343]
[Full Text: https://doi.org/10.1056/NEJM197509252931304]
</p>
</li>
<li>
<p class="mim-text-font">
Horinouchi, K., Erlich, S., Perl, D. P., Ferlinz, K., Bisgaier, C. L., Sandhoff, K., Desnick, R. J., Stewart, C. L., Schuchman, E. H.
<strong>Acid sphingomyelinase deficient mice: a model of types A and B Niemann-Pick disease.</strong>
Nature Genet. 10: 288-293, 1995.
[PubMed: 7670466]
[Full Text: https://doi.org/10.1038/ng0795-288]
</p>
</li>
<li>
<p class="mim-text-font">
Ida, H., Rennert, O. M., Maekawa, K., Eto, Y.
<strong>Identification of three novel mutations in the acid sphingomyelinase gene of Japanese patients with Niemann-Pick disease type A and B.</strong>
Hum. Mutat. 7: 65-67, 1996.
[PubMed: 8664904]
[Full Text: https://doi.org/10.1002/(SICI)1098-1004(1996)7:1&lt;65::AID-HUMU10&gt;3.0.CO;2-Q]
</p>
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<li>
<p class="mim-text-font">
Kampine, J. P., Brady, R. O., Kanfer, J. N.
<strong>Diagnosis of Gaucher&#x27;s disease and Niemann-Pick disease with small samples of venous blood.</strong>
Science 155: 86-88, 1967.
[PubMed: 6015567]
[Full Text: https://doi.org/10.1126/science.155.3758.86]
</p>
</li>
<li>
<p class="mim-text-font">
Kirkegaard, T., Roth, A. G., Petersen, N. H. T., Mahalka, A. K., Olsen, O. D., Moilanen, I., Zylicz, A., Knudsen, J., Sandhoff, K., Arenz, C., Kinnunen, P. K. J., Nylandsted, J., Jaattela, M.
<strong>Hsp70 stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal pathology.</strong>
Nature 463: 549-553, 2010.
[PubMed: 20111001]
[Full Text: https://doi.org/10.1038/nature08710]
</p>
</li>
<li>
<p class="mim-text-font">
Knudson, A. G., Jr., Kaplan, W. D.
<strong>Genetics of the sphingolipidoses. In: Aaronson, S. M.; Volk, B. W.: Cerebral Sphingolipidoses. A Symposium on Tay-Sachs Disease.</strong>
New York: Academic Press (pub.) 1962. Pp. 395-411.
</p>
</li>
<li>
<p class="mim-text-font">
Levran, O., Desnick, R. J., Schuchman, E. H.
<strong>Niemann-Pick disease: a frequent missense mutation in the acid sphingomyelinase gene of Ashkenazi Jewish type A and B patients.</strong>
Proc. Nat. Acad. Sci. 88: 3748-3752, 1991.
[PubMed: 2023926]
[Full Text: https://doi.org/10.1073/pnas.88.9.3748]
</p>
</li>
<li>
<p class="mim-text-font">
Lowden, J. A., Laramee, M. A., Wentworth, P.
<strong>The subacute form of Niemann-Pick disease.</strong>
Arch. Neurol. 17: 230-237, 1967.
[PubMed: 6053566]
[Full Text: https://doi.org/10.1001/archneur.1967.00470270008002]
</p>
</li>
<li>
<p class="mim-text-font">
Lynn, R., Terry, R. D.
<strong>Lipid histochemistry and electron microscopy in adult Niemann-Pick disease.</strong>
Am. J. Med. 37: 987-994, 1964.
[PubMed: 14246098]
[Full Text: https://doi.org/10.1016/0002-9343(64)90139-1]
</p>
</li>
<li>
<p class="mim-text-font">
McGovern, M. M., Aron, A., Brodie, S. E., Desnick, R. J., Wasserstein, M. P.
<strong>Natural history of type A Niemann-Pick disease: possible endpoints for therapeutic trials.</strong>
Neurology 66: 228-232, 2006.
[PubMed: 16434659]
[Full Text: https://doi.org/10.1212/01.wnl.0000194208.08904.0c]
</p>
</li>
<li>
<p class="mim-text-font">
Miyawaki, S., Yoshida, H., Mitsuoka, S., Enomoto, H., Ikehara, S.
<strong>A mouse model for Niemann-Pick disease: influence of genetic background on disease expression in spm/spm mice.</strong>
J. Hered. 77: 379-384, 1986.
[PubMed: 3559164]
[Full Text: https://doi.org/10.1093/oxfordjournals.jhered.a110265]
</p>
</li>
<li>
<p class="mim-text-font">
Oliva, P., Schwarz, M., Mechtler, T. P., Sansen, S., Keutzer, J., Prusa, A. R., Streubel, B., Kasper, D. C.
<strong>Importance to include differential diagnostics for acid sphingomyelinase deficiency (ASMD) in patients suspected to have to Gaucher disease.</strong>
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Pavlu-Pereira, H., Asfaw, B., Poupetova, H., Ledvinova, J., Sikora, J., Vanier, M. T., Sandhoff, K., Zeman, J., Novotna, Z., Chudoba, D., Elleder, M.
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<strong>Bone marrow transplantation for Niemann-Pick mice.</strong>
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<strong>A new form of Niemann-Pick disease characterized by temperature-labile sphingomyelinase.</strong>
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Terry, R. D., Sperry, W. M., Brodoff, B.
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