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Entry
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- #607616 - NIEMANN-PICK DISEASE, TYPE B
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- OMIM
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<p>
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<span class="h4">#607616</span>
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<br />
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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/607616"><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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<a href="#diagnosis">Diagnosis</a>
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<a href="#clinicalManagement">Clinical Management</a>
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<a href="#biochemicalFeatures">Biochemical Features</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<a href="#populationGenetics">Population Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#seeAlso"><strong>See Also</strong></a>
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<li role="presentation">
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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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<a href="#editHistory"><strong>Edit History</strong></a>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div><a href="https://clinicaltrials.gov/search?cond=NIEMANN-PICK DISEASE, TYPE B" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=11106&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.ncbi.nlm.nih.gov/books/NBK1370/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/5227" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=607616[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</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><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=77293" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/disease/DOID:0070112" 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>
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<div><a href="http://www.informatics.jax.org/disease/607616" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0070112" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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<div style="display: table-row">
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</div>
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</a>
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</span>
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<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://catalog.coriell.org/Search?q=OmimNum:607616" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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<span>
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<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.">
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 39390005<br />
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<strong>ICD10CM:</strong> E75.241<br />
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<strong>ORPHA:</strong> 77293<br />
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<strong>DO:</strong> 0070112<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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607616
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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NIEMANN-PICK DISEASE, TYPE B
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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ACID SPHINGOMYELINASE DEFICIENCY, VISCERAL TYPE<br />
|
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ASMD, VISCERAL TYPE
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="includedTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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Other entities represented in this entry:
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</p>
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<div>
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<span class="h3 mim-font">
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NIEMANN-PICK DISEASE, TYPE E, INCLUDED
|
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</span>
|
|
</div>
|
|
|
|
<div>
|
|
<span class="h4 mim-font">
|
|
|
|
NIEMANN-PICK DISEASE, TYPE F, INCLUDED<br />
|
|
NIEMANN-PICK DISEASE, INTERMEDIATE, WITH VISCERAL INVOLVEMENT AND RAPID PROGRESSION, 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 B
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607616"> 607616 </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/607616" 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>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<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/607616" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/607616" 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 (less common) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422065006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422065006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237836003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237836003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237837007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237837007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E34.31" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E34.31</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R62.52" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R62.52</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.43" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.43</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0349588&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0349588</a>, <a href="https://bioportal.bioontology.org/search?q=C0013336&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013336</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003510</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Eyes </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Cherry-red maculae (less common) <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 />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> RESPIRATORY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Lung </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Dyspnea <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/267036007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">267036007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/230145002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">230145002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R06.02" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R06.02</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R06.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R06.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R06.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R06.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/786.05" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">786.05</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013404&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013404</a>, <a href="https://bioportal.bioontology.org/search?q=C2024878&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2024878</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002094" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002094</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002094" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002094</a>]</span><br /> -
|
|
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 /> -
|
|
Decreased pulmonary diffusion secondary to alveolar infiltration <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843427&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843427</a>]</span><br /> -
|
|
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> Liver </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Hepatomegaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80515008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80515008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019209&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019209</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Spleen </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Splenomegaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16294009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16294009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038002&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038002</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001744" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001744</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001744" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001744</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> NEUROLOGIC </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
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<em> Central Nervous System </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Absence of neurologic manifestations <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843419&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843419</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> HEMATOLOGY </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- 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 /> -
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'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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Decreased platelets <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/415116008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">415116008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0392386&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0392386</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> LABORATORY ABNORMALITIES </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Decreased acid sphingomyelinase activity <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 /> -
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Multiple visceral organs (lung, liver, spleen, kidney) contain foamy resident cells and histiocytes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1843423&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1843423</a>]</span><br /> -
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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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Increased LDL cholesterol <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0549399&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0549399</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003141" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003141</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003141" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003141</a>]</span><br /> -
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Increased triglycerides <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/302870006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">302870006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/166848004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">166848004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020557&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020557</a>, <a href="https://bioportal.bioontology.org/search?q=C0813230&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0813230</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002155" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002155</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002155" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002155</a>]</span><br /> -
|
|
Decreased HDL cholesterol <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151691&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151691</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003233" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003233</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003233" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003233</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MISCELLANEOUS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Onset in infancy or childhood<br /> -
|
|
Variable phenotype <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837514&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837514</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003812" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003812</a>]</span><br /> -
|
|
More common in Ashkenazi Jews<br /> -
|
|
Allelic disorder to Niemann-Pick disease type A (<a href="/entry/257200">257200</a>)<br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
|
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<strong> MOLECULAR BASIS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Caused by mutations in the acid lysosomal sphingomyelin phosphodiesterase-1 gene (SMPD1, <a href="/entry/607608#0002">607608.0002</a>)<br />
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</span>
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</div>
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</div>
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</div>
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<div class="text-right">
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
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</div>
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</div>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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</span>
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</span>
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</h4>
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<div id="mimTextFold" class="collapse in ">
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because Niemann-Pick disease type B, known as the 'visceral' form, 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 A (<a href="/entry/257200">257200</a>) is an allelic disorder characterized by onset in infancy of a primarily neurodegenerative disorder with death by age 3 years.</p><p>See also Niemann-Pick disease types C1 (<a href="/entry/257220">257220</a>) and C2 (<a href="/entry/607625">607625</a>).</p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="description" class="mim-anchor"></a>
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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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 a single entity with a clinical spectrum (summary by <a href="#21" class="mim-tip-reference" title="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://doi.org/10.1007/s10545-007-0632-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" 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="#21" class="mim-tip-reference" title="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://doi.org/10.1007/s10545-007-0632-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17632693">Schuchman (2007)</a> provided a detailed review of Niemann-Pick disease type B, 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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<div>
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<br />
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</div>
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<div>
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<a id="clinicalFeatures" class="mim-anchor"></a>
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<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Clinical Features</strong>
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</span>
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</h4>
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</div>
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<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
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<span class="mim-text-font">
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<p>In contrast to patients with Niemann-Pick disease type A, patients with type B have involvement of the spleen, liver, and lungs, and remain free of neurologic manifestations despite the massive visceral involvement. Patients with type B often survive into adulthood.</p><p><a href="#17" class="mim-tip-reference" title="Pfaendler, U. <strong>Nouvelles conceptions sur l'heredite et la pathogenie de la maladie de Niemann-Pick.</strong> Helv. Med. Acta 20: 216-241, 1953.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13095869/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13095869</a>]" pmid="13095869">Pfaendler (1953)</a> described non-Jewish Swiss brothers (out of 14 sibs) with Niemann-Pick disease who died at ages 29 and 33 years; they most likely had type B. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13095869" 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="#3" class="mim-tip-reference" title="Blankenship, R. M., Greenburg, B. R., Lucas, R. N., Reynolds, R. D., Beutler, E. <strong>Familial sea-blue histiocytes with acid phosphatemia: a syndrome resembling Gaucher disease: the Lewis variant.</strong> JAMA 225: 54-56, 1973.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4123476/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4123476</a>]" pmid="4123476">Blankenship et al. (1973)</a> reported a family with sea-blue histiocytosis with acid phosphatemia and suggested that it represented a syndrome similar to Gaucher disease (<a href="/entry/230800">230800</a>). <a href="#7" class="mim-tip-reference" title="Golde, D. W., Schneider, E. L., Bainton, D. F., Pentchev, P. G., Brady, R. O., Epstein, C. J., Cline, M. J. <strong>Pathogenesis of one variant of sea-blue histiocytosis.</strong> Lab. Invest. 33: 371-378, 1975.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1081167/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1081167</a>]" pmid="1081167">Golde et al. (1975)</a> described a second family with sea-blue histiocytosis, lamellar inclusions, and decreased sphingomyelinase activity. <a href="#6" class="mim-tip-reference" title="Fried, K., Beer, S., Krespin, H. I., Leiba, H., Djaldetti, M., Zitman, D., Klibansky, C. <strong>Biochemical, genetic and ultrastructural study of a family with the sea-blue histiocyte syndrome--chronic and non-neuropathic Niemann-Pick disease.</strong> Europ. J. Clin. Invest. 8: 249-253, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/100330/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">100330</a>] [<a href="https://doi.org/10.1111/j.1365-2362.1978.tb00860.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="100330">Fried et al. (1978)</a> presented evidence that primary sea-blue histiocyte disease (<a href="/entry/269600">269600</a>) and Niemann-Pick disease type B are the same. Deficiency of sphingomyelinase could be demonstrated in leukocytes and an intermediate level in heterozygotes. Despite the lack of neurologic symptoms in type B, <a href="#32" class="mim-tip-reference" title="Wenger, D. A., Kudoh, T., Sattler, M., Palmieri, M., Yudkoff, M. <strong>Niemann-Pick disease type B: prenatal diagnosis and enzymatic and chemical studies on fetal brain and liver.</strong> Am. J. Hum. Genet. 33: 337-344, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6264784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6264784</a>]" pmid="6264784">Wenger et al. (1981)</a> were unable to demonstrate lysosomal sphingomyelinase in brain tissue of a fetus affected with type B. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=100330+6264784+4123476+1081167" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Landas, S., Foucar, K., Sando, G. N., Ellefson, R., Hamilton, H. E. <strong>Adult Niemann-Pick disease masquerading as sea blue histiocyte syndrome: report of a case confirmed by lipid analysis and enzyme assays.</strong> Am. J. Hemat. 20: 391-400, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4073013/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4073013</a>] [<a href="https://doi.org/10.1002/ajh.2830200411" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4073013">Landas et al. (1985)</a> reported a 48-year-old woman with debilitating and eventually fatal coronary artery disease and hepatosplenomegaly in whom multiorgan infiltration by sea-blue histiocytes was the consequence of Niemann-Pick disease type B. <a href="#24" class="mim-tip-reference" title="Strisciuglio, P., Di Maio, S., Parenti, G., Franzese, A., Lubrano, P., Mariano, A., Andria, G. <strong>Evidence of polyglandular involvement in Niemann-Pick disease type B.</strong> Europ. J. Pediat. 146: 431-433, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2820735/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2820735</a>] [<a href="https://doi.org/10.1007/BF00444957" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2820735">Strisciuglio et al. (1987)</a> found evidence of involvement of multiple endocrine glands in a patient with type B Niemann-Pick disease and growth failure. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4073013+2820735" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#29" class="mim-tip-reference" title="Viana, M. B., Giugliani, R., Leite, V. H. R., Barth, M. L., Lekhwani, C., Slade, C. M., Fensom, A. <strong>Very low levels of high density lipoprotein cholesterol in four sibs of a family with non-neuropathic Niemann-Pick disease and sea-blue histiocytosis.</strong> J. Med. Genet. 27: 499-504, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2120445/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2120445</a>] [<a href="https://doi.org/10.1136/jmg.27.8.499" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2120445">Viana et al. (1990)</a> reported a Brazilian family in which 4 sibs had sea-blue histiocytosis and nonneuropathic Niemann-Pick disease, presumably type B. The kindred was ascertained through a 7-year-old boy who was found to have massive hepatosplenomegaly since infancy. Four of 12 sibs were similarly affected with short stature, bilateral interstitial pulmonary infiltration, and high levels of serum acid phosphatase. Leukocyte acid sphingomyelinase activity ranged from 3.6 to 6.5% of mean control values, and fibroblast activity from 9 to 13% of mean controls. The parents had low-normal levels. The 4 sibs also had very low levels of low density lipoprotein (LDL) cholesterol, very low levels of high density lipoprotein (HDL) cholesterol, and low levels of apoAI. <a href="#29" class="mim-tip-reference" title="Viana, M. B., Giugliani, R., Leite, V. H. R., Barth, M. L., Lekhwani, C., Slade, C. M., Fensom, A. <strong>Very low levels of high density lipoprotein cholesterol in four sibs of a family with non-neuropathic Niemann-Pick disease and sea-blue histiocytosis.</strong> J. Med. Genet. 27: 499-504, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2120445/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2120445</a>] [<a href="https://doi.org/10.1136/jmg.27.8.499" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2120445">Viana et al. (1990)</a> pointed out that low levels of serum HDL cholesterol have been reported in other patients with Niemann-Pick disease and may be a secondary manifestation of the lysosomal storage disease since low serum HDL cholesterol has been found in at least 2 other diseases in this category, namely, Gaucher disease and cholesteryl ester storage disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2120445" 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="#30" class="mim-tip-reference" title="Volders, P., Van Hove, J., Lories, R. J. U., Vandekerckhove, P., Matthijs, G., De Vos, R., Vanier, M. T., Vincent, M. F., Westhovens, R., Luyten, F. P. <strong>Niemann-Pick disease type B: an unusual clinical presentation with multiple vertebral fractures.</strong> Am. J. Med. Genet. 109: 42-51, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11932991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11932991</a>] [<a href="https://doi.org/10.1002/ajmg.10278" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11932991">Volders et al. (2002)</a> reported a unique case of a 55-year-old woman who presented with a clinical picture of Parkinson disease, severe back pain, splenomegaly, and pronounced dyspnea. Radiographic examination of the spine showed multiple vertebral fractures. Niemann-Pick disease type B was diagnosed by the finding of lipid-loaded histiocytes and strongly reduced sphingomyelinase activity. She was found to be homozygous for a mutation in the SMPD1 gene (<a href="/entry/607608#0002">607608.0002</a>); see MOLECULAR GENETICS. In this patient, <a href="#30" class="mim-tip-reference" title="Volders, P., Van Hove, J., Lories, R. J. U., Vandekerckhove, P., Matthijs, G., De Vos, R., Vanier, M. T., Vincent, M. F., Westhovens, R., Luyten, F. P. <strong>Niemann-Pick disease type B: an unusual clinical presentation with multiple vertebral fractures.</strong> Am. J. Med. Genet. 109: 42-51, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11932991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11932991</a>] [<a href="https://doi.org/10.1002/ajmg.10278" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11932991">Volders et al. (2002)</a> screened for polymorphisms previously described as possibly associated with increased risk for osteoporosis and fractures and found that the patient was heterozygous for polymorphisms of the vitamin D receptor gene (VDR; <a href="/entry/601769">601769</a>), the estrogen receptor gene (ESR1; <a href="/entry/133430">133430</a>), and the alpha-1 chain of type I collagen (COL1A1; <a href="/entry/120150">120150</a>). The dramatic presentation of the patient was thought to be explained by increased physical activity after treatment of Parkinson disease, a genetic predisposition, and worsening of the disease due to interfering medication. She was treated with cholesterol-lowering drugs such as statins to decrease sphingomyelin synthesis, avoidance of drugs that can inhibit sphingomyelinase, and bisphosphonates. No new fractures occurred, but the interstitial lung disease progressed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11932991" 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="McGovern, M. M., Lippa, N., Bagiella, E., Schuchman, E. H., Desnick, R. J., Wasserstein, M. P. <strong>Morbidity and mortality in type B Niemann-Pick disease.</strong> Genet. Med. 15: 618-623, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23412609/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23412609</a>] [<a href="https://doi.org/10.1038/gim.2013.4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23412609">McGovern et al. (2013)</a> performed a systematic evaluation of morbidity and mortality in Niemann-Pick type B disease in a total of 103 patients (49 males, 54 females, age range 1-72 years) studied between 1992 and 2012. Serious morbidities included significant neurologic, hepatic, and cardiac disease. Thirteen patients had some degree of neurologic impairment. Nine had cirrhosis or liver failure requiring transplantation. Coronary artery and valvular heart disease were present in 9 patients. Of note, only 4 patients were oxygen-dependent, although progressive pulmonary disease is a well-described feature of Niemann-Pick disease. During the follow-up period 18 deaths occurred. Median age of death was 15.5 years (range 1-72). Causes of death included pneumonia, liver failure, and hemorrhage. The majority of deaths (12 of the 18) occurred in patients younger than 21 years, yielding a mortality rate of 19% in the pediatric population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23412609" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Cassiman, D., Packman, S., Bembi, B., Ben Turkia, H., Al-Sayed, M., Schiff, M., Imrie, J., Mabe, P., Takahashi, T., Mengel, K. E., Giugliani, R., Cox, G. F. <strong>Cause of death in patients with chronic visceral and chronic neurovisceral acid sphingomyelinase deficiency (Niemann-Pick disease type B and B variant): literature review and report of new cases.</strong> Molec. Genet. Metab. 118: 206-213, 2016. Note: Erratum: Molec. Genet. Metab. 125: 360 only, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27198631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27198631</a>] [<a href="https://doi.org/10.1016/j.ymgme.2016.05.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27198631">Cassiman et al. (2016)</a> reviewed the cause of death in 85 patients with Niemann-Pick B and B variant. Of these, 27 were newly reported and 58 were abstracted from the literature. Common disease-related morbidities included splenomegaly (97%), hepatomegaly (91%), liver dysfunction (83%), and pulmonary disease (75%). Among those with symptom onset after 18 years of age, respiratory disease was the primary cause of death in 44%, with bleeding and cardiac disease each accounting for 22%. Among those with symptom onset before 18 years of age, respiratory disease and liver disease each accounted for 28% of deaths and neurodegenerative disease accounted for 15% of deaths. Among those with chronic visceral acid sphingomyelinase deficiency (ASMD), respiratory disease and liver disease accounted for 31% and 29% of deaths, respectively. Among those with chronic neurovisceral ASMD, respiratory and neurodegenerative disease each accounted for 23% of deaths and were followed by liver disease at 19%. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27198631" 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>
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<a href="#16" 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. <strong>Acid sphingomyelinase deficiency. Phenotype variability with prevalence of intermediate phenotype in a series of twenty-five Czech and Slovak patients. A multi-approach study.</strong> J. Inherit. Metab. Dis. 28: 203-227, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15877209/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15877209</a>] [<a href="https://doi.org/10.1007/s10545-005-5671-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" 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="#16" 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. <strong>Acid sphingomyelinase deficiency. Phenotype variability with prevalence of intermediate phenotype in a series of twenty-five Czech and Slovak patients. A multi-approach study.</strong> J. Inherit. Metab. Dis. 28: 203-227, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15877209/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15877209</a>] [<a href="https://doi.org/10.1007/s10545-005-5671-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" 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><p><strong><em>Niemann-Pick Disease, Types E and F</em></strong></p><p>
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<a href="#27" class="mim-tip-reference" title="Terry, R. D., Sperry, W. M., Brodoff, B. <strong>Adult lipidosis resembling Niemann-Pick's disease.</strong> Am. J. Path. 30: 263-285, 1954.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13138710/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13138710</a>]" pmid="13138710">Terry et al. (1954)</a> and <a href="#12" class="mim-tip-reference" title="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: <a href="https://pubmed.ncbi.nlm.nih.gov/14246098/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14246098</a>] [<a href="https://doi.org/10.1016/0002-9343(64)90139-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14246098">Lynn and Terry (1964)</a> described an indeterminate adult form of Niemann-Pick disease, type E. Type E patients are adults with moderate hepatosplenomegaly and some increase in sphingomyelin in the liver, spleen, and bone marrow. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=13138710+14246098" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#20" class="mim-tip-reference" title="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.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/216805/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">216805</a>] [<a href="https://doi.org/10.1136/jmg.15.5.370" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="216805">Schneider et al. (1978)</a> used the designation type F for a form characterized in 2 patients by childhood onset of splenomegaly, lack of neurologic involvement, diminished sphingomyelinase activity, and thermolabile enzyme. Niemann-Pick disease types E and F have not been well-characterized. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=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>
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<p><a href="#22" class="mim-tip-reference" title="Simonaro, C. M., Desnick, R. J., McGovern, M. M., Wasserstein, M. P., Schuchman, E. H. <strong>The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations.</strong> Am. J. Hum. Genet. 71: 1413-1419, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12369017/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12369017</a>] [<a href="https://doi.org/10.1086/345074" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12369017">Simonaro et al. (2002)</a> commented that type B Niemann-Pick disease is a particularly difficult disorder to diagnose clinically. They suggested that it might be useful to screen in heart disease clinics for patients with very low HDL cholesterol levels, since this is a common finding in almost all patients with type B Niemann-Pick disease, or in endocrinology clinics where patients may be seen for growth retardation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12369017" 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="#15" class="mim-tip-reference" title="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.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/37086570/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">37086570</a>] [<a href="https://doi.org/10.1016/j.ymgme.2023.107563" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" 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="#15" class="mim-tip-reference" title="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.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/37086570/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">37086570</a>] [<a href="https://doi.org/10.1016/j.ymgme.2023.107563" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" 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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<p>Following the lead of <a href="#1" class="mim-tip-reference" title="Adinolfi, M., Akle, C. A., McColl, I., Fensom, A. H., Tansley, L., Connolly, P., Hsi, B.-L., Faulk, W. P., Travers, P., Bodmer, W. F. <strong>Expression of HLA antigens, beta-2-microglobulin and enzymes by human amniotic epithelial cells.</strong> Nature 295: 325-327, 1982.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6173762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6173762</a>] [<a href="https://doi.org/10.1038/295325a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6173762">Adinolfi et al. (1982)</a>, who proposed the transplantation of amniotic membrane in the treatment of patients with lysosomal storage disorders, <a href="#2" class="mim-tip-reference" title="Bembi, B., Comelli, M., Scaggiante, B., Pineschi, A., Rapelli, S., Gornati, R., Montorfano, G., Berra, B., Agosti, E., Romeo, D. <strong>Treatment of sphingomyelinase deficiency by repeated implantations of amniotic epithelial cells.</strong> Am. J. Med. Genet. 44: 527-533, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1442900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1442900</a>] [<a href="https://doi.org/10.1002/ajmg.1320440430" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1442900">Bembi et al. (1992)</a> treated 5 young patients with Niemann-Pick disease type B with repeated implantations of amniotic epithelial cells as a source of exogenous sphingomyelinase. They concluded that the treatment abolished recurrent infections, mainly of the respiratory tract, and led to other improvements in the general condition of the patients. In 2 cases with increased sphingomyelin in urinary sediments, a single implantation caused a sustained normalization of sphingomyelin and total phospholipids in the urine. Furthermore, a rise in sphingomyelinase activity in peripheral leukocytes to values in the heterozygous range were observed. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1442900+6173762" 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="#19" class="mim-tip-reference" title="Scaggiante, B., Pineschi, A., Sustersich, M., Andolina, M., Agosti, E., Romeo, D. <strong>Successful therapy of Niemann-Pick disease by implantation of human amniotic membrane.</strong> Transplantation 44: 59-61, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3037739/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3037739</a>] [<a href="https://doi.org/10.1097/00007890-198707000-00014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3037739">Scaggiante et al. (1987)</a> used repeated subcutaneous implantations of amniotic membrane to restore enzyme in a 14-year-old boy with Niemann-Pick disease type B. The patient had massive hepatosplenomegaly and diffuse infiltration of the lungs. Decrease in hepatomegaly was observed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3037739" 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="#31" class="mim-tip-reference" title="Wang, R. Y., Bodamer, O. A., Watson, M. S., Wilcox, W. R. <strong>Lysosomal storage diseases: diagnostic confirmation and management of presymptomatic individuals.</strong> Genet. Med. 13: 457-484, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21502868/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21502868</a>] [<a href="https://doi.org/10.1097/GIM.0b013e318211a7e1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" 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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<p><a href="#9" 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. <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://doi.org/10.1038/nature08710" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" 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 (<a href="/entry/257200">257200</a>) and B, 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="#9" 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. <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://doi.org/10.1038/nature08710" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" 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>
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<p>In an Ashkenazi Jewish patient with Niemann-Pick disease type B, <a href="#11" class="mim-tip-reference" title="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: <a href="https://pubmed.ncbi.nlm.nih.gov/2023926/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2023926</a>] [<a href="https://doi.org/10.1073/pnas.88.9.3748" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2023926">Levran et al. (1991)</a> identified a mutation in the acid lysosomal sphingomyelinase phosphodiesterase-1 gene (<a href="/entry/607608#0002">607608.0002</a>). <a href="#25" class="mim-tip-reference" title="Takahashi, T., Desnick, R. J., Takada, G., Schuchman, E. H. <strong>Identification of a missense mutation (S436R) in the acid sphingomyelinase gene from a Japanese patient with type B Niemann-Pick disease.</strong> Hum. Mutat. 1: 70-71, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1301192/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1301192</a>] [<a href="https://doi.org/10.1002/humu.1380010111" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1301192">Takahashi et al. (1992)</a> identified 3 SMPD1 mutations (<a href="/entry/607608#0008">607608.0008</a>-<a href="/entry/607608#0009">607608.0009</a>) causing Niemann-Pick disease type B. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2023926+1301192" 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="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.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19405096/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19405096</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=19405096[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/humu.21018" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" 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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<p><a href="#26" class="mim-tip-reference" title="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> J. Biol. Chem. 267: 12552-12558, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1618760/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1618760</a>]" 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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<p><a href="#22" class="mim-tip-reference" title="Simonaro, C. M., Desnick, R. J., McGovern, M. M., Wasserstein, M. P., Schuchman, E. H. <strong>The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations.</strong> Am. J. Hum. Genet. 71: 1413-1419, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12369017/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12369017</a>] [<a href="https://doi.org/10.1086/345074" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12369017">Simonaro et al. (2002)</a> collected demographic and/or mutation information on a worldwide sample of 394 patients with type B Niemann-Pick disease. They found that the disorder is panethnic, with the highest incidence occurring in individuals of Turkish, Arab, and North African descent. Only 5 of the 394 patients were Ashkenazi Jewish, revealing that, unlike the type A form of Niemann-Pick disease, type B does not occur frequently within this population. Mutation analysis of the SMPD1 gene was performed on 228 patients and several novel 'common' mutations were found. The previously reported arg608-to-del mutation (<a href="/entry/607608#0002">607608.0002</a>) occurred in approximately 12% of the alleles studied. Overall, a total of 45 novel mutations were found, and several new genotype/phenotype correlations were identified. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12369017" 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>Using a novel transgenic/knockout strategy to manipulate the intracellular targeting of a hydrolase, <a href="#13" class="mim-tip-reference" title="Marathe, S., Miranda, S. R. P., Devlin, C., Johns, A., Kuriakose, G., Williams, K. J., Schuchman, E. H., Tabas, I. <strong>Creation of a mouse model for non-neurological (type B) Niemann-Pick disease by stable, low level expression of lysosomal sphingomyelinase in the absence of secretory sphingomyelinase: relationship between brain intra-lysosomal enzyme activity and central nervous system function.</strong> Hum. Molec. Genet. 9: 1967-1976, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10942425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10942425</a>] [<a href="https://doi.org/10.1093/hmg/9.13.1967" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10942425">Marathe et al. (2000)</a> created a mouse that stably expresses low levels of lysosomal sphingomyelinase (L-SMase) in the complete absence of secretory sphingomyelinase (S-SMase). The brains of these mice exhibited 11.5 to 18.2% of wildtype L-SMase activity, but the cerebellar Purkinje cell layer, which is lost by 4 months of age in mice completely lacking L- and S-SMase, was preserved for at least 8 months. The L-SMase activities in other organs were 1 to 14% of wildtype levels, and by 8 months of age all peripheral organs had accumulated sphingomyelin and demonstrated pathologic intracellular inclusions. Most importantly, L-SMase-expressing mice showed no signs of the severe neurologic disease observed in completely deficient mice, and their life span and general health were essentially normal. The authors concluded that stable, continuous, low level expression of intralysosomal enzyme activity in the brain may preserve CNS function in the absence of secretory enzyme or other confounding factors. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10942425" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#Breen1981" class="mim-tip-reference" title="Breen, L., Morris, H. H., Alperin, J. B., Schochet, S. S., Jr. <strong>Juvenile Niemann-Pick disease with vertical supranuclear ophthalmoplegia: two case reports and review of the literature.</strong> Arch. Neurol. 38: 388-390, 1981.">Breen et al. (1981)</a>; <a href="#Kampine1967" class="mim-tip-reference" title="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.">Kampine et al. (1967)</a>; <a href="#Sogawa1978" class="mim-tip-reference" title="Sogawa, H., Horino, K., Nakamura, F., Kudoh, T., Oyanagi, K., Yamanouchi, T., Minami, R., Nakao, T., Watanabe, A., Matsuura, Y. <strong>Chronic Niemann-Pick disease with sphingomyelinase deficiency in two brothers with mental retardation.</strong> Europ. J. Pediat. 128: 235-240, 1978.">Sogawa et al. (1978)</a>; <a href="#Vanier1985" class="mim-tip-reference" title="Vanier, M. T., Boue, J., Dumez, Y. <strong>Niemann-Pick disease type B: first-trimester prenatal diagnosis on chorionic villi and biochemical study of a foetus at 12 weeks of development.</strong> Clin. Genet. 28: 348-354, 1985.">Vanier et al. (1985)</a>
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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.
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[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>]
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[<a href="https://doi.org/10.1002/ajh.2830200411" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2023926/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2023926</a>, <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'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.88.9.3748" target="_blank">Full Text</a>]
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Marathe, S., Miranda, S. R. P., Devlin, C., Johns, A., Kuriakose, G., Williams, K. J., Schuchman, E. H., Tabas, I.
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<strong>Creation of a mouse model for non-neurological (type B) Niemann-Pick disease by stable, low level expression of lysosomal sphingomyelinase in the absence of secretory sphingomyelinase: relationship between brain intra-lysosomal enzyme activity and central nervous system function.</strong>
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Hum. Molec. Genet. 9: 1967-1976, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10942425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10942425</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10942425" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/9.13.1967" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/gim.2013.4" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2023.107563" target="_blank">Full Text</a>]
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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 href="https://doi.org/10.1136/jmg.15.5.370" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s10545-007-0632-9" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1086/345074" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00444957" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/humu.1380010111" target="_blank">Full Text</a>]
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Genet. Med. 13: 457-484, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21502868/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21502868</a>, <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'})">related citations</a>]
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[<a href="https://doi.org/10.1097/GIM.0b013e318211a7e1" target="_blank">Full Text</a>]
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Wenger, D. A., Kudoh, T., Sattler, M., Palmieri, M., Yudkoff, M.
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<strong>Niemann-Pick disease type B: prenatal diagnosis and enzymatic and chemical studies on fetal brain and liver.</strong>
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Am. J. Hum. Genet. 33: 337-344, 1981.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6264784/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6264784</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6264784" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Hilary J. Vernon - updated : 05/25/2023
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Ada Hamosh - updated : 12/14/2016<br>Ada Hamosh - updated : 11/12/2013<br>Ada Hamosh - updated : 10/4/2012<br>Ada Hamosh - updated : 3/9/2010<br>Cassandra L. Kniffin - updated : 11/11/2009<br>Cassandra L. Kniffin - updated : 1/7/2009
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Cassandra L. Kniffin : 3/7/2003
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carol : 05/25/2023
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carol : 01/20/2022<br>carol : 02/26/2021<br>carol : 02/15/2021<br>alopez : 04/09/2019<br>alopez : 12/14/2016<br>carol : 10/19/2016<br>alopez : 11/12/2013<br>alopez : 10/4/2012<br>alopez : 3/10/2010<br>terry : 3/9/2010<br>wwang : 12/3/2009<br>ckniffin : 11/11/2009<br>terry : 6/3/2009<br>wwang : 1/21/2009<br>ckniffin : 1/7/2009<br>ckniffin : 3/13/2003<br>carol : 3/13/2003<br>ckniffin : 3/13/2003
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<strong>#</strong> 607616
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NIEMANN-PICK DISEASE, TYPE B
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ACID SPHINGOMYELINASE DEFICIENCY, VISCERAL TYPE<br />
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ASMD, VISCERAL TYPE
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Other entities represented in this entry:
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NIEMANN-PICK DISEASE, TYPE E, INCLUDED
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NIEMANN-PICK DISEASE, TYPE F, INCLUDED<br />
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NIEMANN-PICK DISEASE, INTERMEDIATE, WITH VISCERAL INVOLVEMENT AND RAPID PROGRESSION, INCLUDED
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<strong>SNOMEDCT:</strong> 39390005;
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<strong>ICD10CM:</strong> E75.241;
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<strong>ORPHA:</strong> 77293;
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<strong>DO:</strong> 0070112;
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11p15.4
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Niemann-Pick disease, type B
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607616
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Autosomal recessive
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607608
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<p>A number sign (#) is used with this entry because Niemann-Pick disease type B, known as the 'visceral' form, 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 A (257200) is an allelic disorder characterized by onset in infancy of a primarily neurodegenerative disorder with death by age 3 years.</p><p>See also Niemann-Pick disease types C1 (257220) and C2 (607625).</p>
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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 a single entity with a clinical spectrum (summary by Schuchman, 2007). </p><p>Schuchman (2007) provided a detailed review of Niemann-Pick disease type B, including clinical management. </p>
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<p>In contrast to patients with Niemann-Pick disease type A, patients with type B have involvement of the spleen, liver, and lungs, and remain free of neurologic manifestations despite the massive visceral involvement. Patients with type B often survive into adulthood.</p><p>Pfaendler (1953) described non-Jewish Swiss brothers (out of 14 sibs) with Niemann-Pick disease who died at ages 29 and 33 years; they most likely had type B. </p><p>Blankenship et al. (1973) reported a family with sea-blue histiocytosis with acid phosphatemia and suggested that it represented a syndrome similar to Gaucher disease (230800). Golde et al. (1975) described a second family with sea-blue histiocytosis, lamellar inclusions, and decreased sphingomyelinase activity. Fried et al. (1978) presented evidence that primary sea-blue histiocyte disease (269600) and Niemann-Pick disease type B are the same. Deficiency of sphingomyelinase could be demonstrated in leukocytes and an intermediate level in heterozygotes. Despite the lack of neurologic symptoms in type B, Wenger et al. (1981) were unable to demonstrate lysosomal sphingomyelinase in brain tissue of a fetus affected with type B. </p><p>Landas et al. (1985) reported a 48-year-old woman with debilitating and eventually fatal coronary artery disease and hepatosplenomegaly in whom multiorgan infiltration by sea-blue histiocytes was the consequence of Niemann-Pick disease type B. Strisciuglio et al. (1987) found evidence of involvement of multiple endocrine glands in a patient with type B Niemann-Pick disease and growth failure. </p><p>Viana et al. (1990) reported a Brazilian family in which 4 sibs had sea-blue histiocytosis and nonneuropathic Niemann-Pick disease, presumably type B. The kindred was ascertained through a 7-year-old boy who was found to have massive hepatosplenomegaly since infancy. Four of 12 sibs were similarly affected with short stature, bilateral interstitial pulmonary infiltration, and high levels of serum acid phosphatase. Leukocyte acid sphingomyelinase activity ranged from 3.6 to 6.5% of mean control values, and fibroblast activity from 9 to 13% of mean controls. The parents had low-normal levels. The 4 sibs also had very low levels of low density lipoprotein (LDL) cholesterol, very low levels of high density lipoprotein (HDL) cholesterol, and low levels of apoAI. Viana et al. (1990) pointed out that low levels of serum HDL cholesterol have been reported in other patients with Niemann-Pick disease and may be a secondary manifestation of the lysosomal storage disease since low serum HDL cholesterol has been found in at least 2 other diseases in this category, namely, Gaucher disease and cholesteryl ester storage disease. </p><p>Volders et al. (2002) reported a unique case of a 55-year-old woman who presented with a clinical picture of Parkinson disease, severe back pain, splenomegaly, and pronounced dyspnea. Radiographic examination of the spine showed multiple vertebral fractures. Niemann-Pick disease type B was diagnosed by the finding of lipid-loaded histiocytes and strongly reduced sphingomyelinase activity. She was found to be homozygous for a mutation in the SMPD1 gene (607608.0002); see MOLECULAR GENETICS. In this patient, Volders et al. (2002) screened for polymorphisms previously described as possibly associated with increased risk for osteoporosis and fractures and found that the patient was heterozygous for polymorphisms of the vitamin D receptor gene (VDR; 601769), the estrogen receptor gene (ESR1; 133430), and the alpha-1 chain of type I collagen (COL1A1; 120150). The dramatic presentation of the patient was thought to be explained by increased physical activity after treatment of Parkinson disease, a genetic predisposition, and worsening of the disease due to interfering medication. She was treated with cholesterol-lowering drugs such as statins to decrease sphingomyelin synthesis, avoidance of drugs that can inhibit sphingomyelinase, and bisphosphonates. No new fractures occurred, but the interstitial lung disease progressed. </p><p>McGovern et al. (2013) performed a systematic evaluation of morbidity and mortality in Niemann-Pick type B disease in a total of 103 patients (49 males, 54 females, age range 1-72 years) studied between 1992 and 2012. Serious morbidities included significant neurologic, hepatic, and cardiac disease. Thirteen patients had some degree of neurologic impairment. Nine had cirrhosis or liver failure requiring transplantation. Coronary artery and valvular heart disease were present in 9 patients. Of note, only 4 patients were oxygen-dependent, although progressive pulmonary disease is a well-described feature of Niemann-Pick disease. During the follow-up period 18 deaths occurred. Median age of death was 15.5 years (range 1-72). Causes of death included pneumonia, liver failure, and hemorrhage. The majority of deaths (12 of the 18) occurred in patients younger than 21 years, yielding a mortality rate of 19% in the pediatric population. </p><p>Cassiman et al. (2016) reviewed the cause of death in 85 patients with Niemann-Pick B and B variant. Of these, 27 were newly reported and 58 were abstracted from the literature. Common disease-related morbidities included splenomegaly (97%), hepatomegaly (91%), liver dysfunction (83%), and pulmonary disease (75%). Among those with symptom onset after 18 years of age, respiratory disease was the primary cause of death in 44%, with bleeding and cardiac disease each accounting for 22%. Among those with symptom onset before 18 years of age, respiratory disease and liver disease each accounted for 28% of deaths and neurodegenerative disease accounted for 15% of deaths. Among those with chronic visceral acid sphingomyelinase deficiency (ASMD), respiratory disease and liver disease accounted for 31% and 29% of deaths, respectively. Among those with chronic neurovisceral ASMD, respiratory and neurodegenerative disease each accounted for 23% of deaths and were followed by liver disease at 19%. </p><p><strong><em>Clinical Variability</em></strong></p><p>
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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><p><strong><em>Niemann-Pick Disease, Types E and F</em></strong></p><p>
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Terry et al. (1954) and Lynn and Terry (1964) described an indeterminate adult form of Niemann-Pick disease, type E. Type E patients are adults with moderate hepatosplenomegaly and some increase in sphingomyelin in the liver, spleen, and bone marrow. </p><p>Schneider et al. (1978) used the designation type F for a form characterized in 2 patients by childhood onset of splenomegaly, lack of neurologic involvement, diminished sphingomyelinase activity, and thermolabile enzyme. Niemann-Pick disease types E and F have not been well-characterized. </p>
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<h4>
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<span class="mim-font">
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<strong>Diagnosis</strong>
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<p>Simonaro et al. (2002) commented that type B Niemann-Pick disease is a particularly difficult disorder to diagnose clinically. They suggested that it might be useful to screen in heart disease clinics for patients with very low HDL cholesterol levels, since this is a common finding in almost all patients with type B Niemann-Pick disease, or in endocrinology clinics where patients may be seen for growth retardation. </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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<p>Following the lead of Adinolfi et al. (1982), who proposed the transplantation of amniotic membrane in the treatment of patients with lysosomal storage disorders, Bembi et al. (1992) treated 5 young patients with Niemann-Pick disease type B with repeated implantations of amniotic epithelial cells as a source of exogenous sphingomyelinase. They concluded that the treatment abolished recurrent infections, mainly of the respiratory tract, and led to other improvements in the general condition of the patients. In 2 cases with increased sphingomyelin in urinary sediments, a single implantation caused a sustained normalization of sphingomyelin and total phospholipids in the urine. Furthermore, a rise in sphingomyelinase activity in peripheral leukocytes to values in the heterozygous range were observed. </p><p>Scaggiante et al. (1987) used repeated subcutaneous implantations of amniotic membrane to restore enzyme in a 14-year-old boy with Niemann-Pick disease type B. The patient had massive hepatosplenomegaly and diffuse infiltration of the lungs. Decrease in hepatomegaly was observed. </p><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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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Biochemical Features</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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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 (257200) and B, 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>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>In an Ashkenazi Jewish patient with Niemann-Pick disease type B, Levran et al. (1991) identified a mutation in the acid lysosomal sphingomyelinase phosphodiesterase-1 gene (607608.0002). Takahashi et al. (1992) identified 3 SMPD1 mutations (607608.0008-607608.0009) causing Niemann-Pick disease type B. </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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</span>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Genotype/Phenotype Correlations</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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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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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Population Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Simonaro et al. (2002) collected demographic and/or mutation information on a worldwide sample of 394 patients with type B Niemann-Pick disease. They found that the disorder is panethnic, with the highest incidence occurring in individuals of Turkish, Arab, and North African descent. Only 5 of the 394 patients were Ashkenazi Jewish, revealing that, unlike the type A form of Niemann-Pick disease, type B does not occur frequently within this population. Mutation analysis of the SMPD1 gene was performed on 228 patients and several novel 'common' mutations were found. The previously reported arg608-to-del mutation (607608.0002) occurred in approximately 12% of the alleles studied. Overall, a total of 45 novel mutations were found, and several new genotype/phenotype correlations were identified. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Using a novel transgenic/knockout strategy to manipulate the intracellular targeting of a hydrolase, Marathe et al. (2000) created a mouse that stably expresses low levels of lysosomal sphingomyelinase (L-SMase) in the complete absence of secretory sphingomyelinase (S-SMase). The brains of these mice exhibited 11.5 to 18.2% of wildtype L-SMase activity, but the cerebellar Purkinje cell layer, which is lost by 4 months of age in mice completely lacking L- and S-SMase, was preserved for at least 8 months. The L-SMase activities in other organs were 1 to 14% of wildtype levels, and by 8 months of age all peripheral organs had accumulated sphingomyelin and demonstrated pathologic intracellular inclusions. Most importantly, L-SMase-expressing mice showed no signs of the severe neurologic disease observed in completely deficient mice, and their life span and general health were essentially normal. The authors concluded that stable, continuous, low level expression of intralysosomal enzyme activity in the brain may preserve CNS function in the absence of secretory enzyme or other confounding factors. </p>
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>See Also:</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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Breen et al. (1981); Kampine et al. (1967); Sogawa et al. (1978);
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Vanier et al. (1985)
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</h4>
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<strong>Expression of HLA antigens, beta-2-microglobulin and enzymes by human amniotic epithelial cells.</strong>
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Nature 295: 325-327, 1982.
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<strong>Treatment of sphingomyelinase deficiency by repeated implantations of amniotic epithelial cells.</strong>
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Science 155: 86-88, 1967.
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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.
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<strong>Hsp70 stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal pathology.</strong>
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<strong>Creation of a mouse model for non-neurological (type B) Niemann-Pick disease by stable, low level expression of lysosomal sphingomyelinase in the absence of secretory sphingomyelinase: relationship between brain intra-lysosomal enzyme activity and central nervous system function.</strong>
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<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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[PubMed: 13095869]
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Rodriguez-Pascau, L., Gort, L., Schuchman, E. H., Vilagelui, L., Grinberg, D., Chabas, A.
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Scaggiante, B., Pineschi, A., Sustersich, M., Andolina, M., Agosti, E., Romeo, D.
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<strong>Successful therapy of Niemann-Pick disease by implantation of human amniotic membrane.</strong>
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Transplantation 44: 59-61, 1987.
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[PubMed: 3037739]
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<p class="mim-text-font">
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Schneider, E. L., Pentchev, P. G., Hibbert, S. R., Sawitsky, A., Brady, R. O.
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<strong>A new form of Niemann-Pick disease characterized by temperature-labile sphingomyelinase.</strong>
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J. Med. Genet. 15: 370-374, 1978.
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[PubMed: 216805]
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[Full Text: https://doi.org/10.1136/jmg.15.5.370]
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</p>
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<li>
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<p class="mim-text-font">
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Schuchman, E. H.
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<strong>The pathogenesis and treatment of acid sphingomyelinase-deficient Niemann-Pick disease.</strong>
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J. Inherit. Metab. Dis. 30: 654-663, 2007.
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[PubMed: 17632693]
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[Full Text: https://doi.org/10.1007/s10545-007-0632-9]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Simonaro, C. M., Desnick, R. J., McGovern, M. M., Wasserstein, M. P., Schuchman, E. H.
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<strong>The demographics and distribution of type B Niemann-Pick disease: novel mutations lead to new genotype/phenotype correlations.</strong>
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Am. J. Hum. Genet. 71: 1413-1419, 2002.
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[PubMed: 12369017]
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Takahashi, T., Suchi, M., Desnick, R. J., Takada, G., Schuchman, E. H.
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<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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<strong>Adult lipidosis resembling Niemann-Pick's disease.</strong>
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Vanier, M. T., Boue, J., Dumez, Y.
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Volders, P., Van Hove, J., Lories, R. J. U., Vandekerckhove, P., Matthijs, G., De Vos, R., Vanier, M. T., Vincent, M. F., Westhovens, R., Luyten, F. P.
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<strong>Niemann-Pick disease type B: an unusual clinical presentation with multiple vertebral fractures.</strong>
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Wang, R. Y., Bodamer, O. A., Watson, M. S., Wilcox, W. R.
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Wenger, D. A., Kudoh, T., Sattler, M., Palmieri, M., Yudkoff, M.
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<strong>Niemann-Pick disease type B: prenatal diagnosis and enzymatic and chemical studies on fetal brain and liver.</strong>
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Hilary J. Vernon - updated : 05/25/2023<br>Ada Hamosh - updated : 12/14/2016<br>Ada Hamosh - updated : 11/12/2013<br>Ada Hamosh - updated : 10/4/2012<br>Ada Hamosh - updated : 3/9/2010<br>Cassandra L. Kniffin - updated : 11/11/2009<br>Cassandra L. Kniffin - updated : 1/7/2009
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