4311 lines
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Entry
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- #268800 - SANDHOFF DISEASE
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- OMIM
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<p>
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<span class="h4">#268800</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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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/268800"><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="#heterogeneity">Heterogeneity</a>
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<a href="#diagnosis">Diagnosis</a>
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<a href="#pathogenesis">Pathogenesis</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#populationGenetics">Population Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#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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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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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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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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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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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://clinicaltrials.gov/search?cond=SANDHOFF DISEASE" 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="#mimEuroGentestFold" id="mimEuroGentestToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A list of European laboratories that offer genetic testing."><span id="mimEuroGentestToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>EuroGentest</div>
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<div id="mimEuroGentestFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=21353&Typ=Pat" title="Sandhoff disease, infantile form" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Sandhoff disease, infantil… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=21354&Typ=Pat" title="Sandhoff disease, juvenile form" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Sandhoff disease, juvenile… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=21355&Typ=Pat" title="Sandhoff disease, adult form" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Sandhoff disease, adult fo… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=38&Typ=Pat" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Sandhoff disease </a></div>
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</div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK579484/" 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/6408" 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://medlineplus.gov/genetics/condition/sandhoff-disease" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=268800[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="#mimOrphanetFold" id="mimOrphanetToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="European reference portal for information on rare diseases and orphan drugs."><span id="mimOrphanetToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Orphanet</div>
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<div id="mimOrphanetFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=309155" title="Sandhoff disease, infantile form" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Sandhoff disease, infantil…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=309162" title="Sandhoff disease, juvenile form" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Sandhoff disease, juvenile…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=309169" title="Sandhoff disease, adult form" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Sandhoff disease, adult fo…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=796" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Sandhoff disease</a></div>
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</div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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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 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:3323" 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/268800" 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://omia.org/OMIA001462/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:3323" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" 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="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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</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="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:268800" 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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<a id="title" class="mim-anchor"></a>
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<a id="number" class="mim-anchor"></a>
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 23849003<br />
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<strong>ICD10CM:</strong> E75.01<br />
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<strong>ORPHA:</strong> 309155, 309162, 309169, 796<br />
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<strong>DO:</strong> 3323<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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268800
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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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SANDHOFF DISEASE
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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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GM2-GANGLIOSIDOSIS, TYPE II<br />
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HEXOSAMINIDASES A AND B DEFICIENCY
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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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</span>
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</p>
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</div>
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<div>
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<span class="h3 mim-font">
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SANDHOFF DISEASE, ADULT TYPE, INCLUDED
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</span>
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</div>
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<div>
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<span class="h4 mim-font">
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SANDHOFF DISEASE, JUVENILE TYPE, INCLUDED<br />
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SANDHOFF DISEASE, INFANTILE TYPE, INCLUDED
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</span>
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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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<div>
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<a id="phenotypeMap" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>Phenotype-Gene Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/5/253?start=-3&limit=10&highlight=253">
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5q13.3
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</a>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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Sandhoff disease, infantile, juvenile, and adult forms
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<a href="/entry/268800"> 268800 </a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
|
HEXB
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
|
<a href="/entry/606873"> 606873 </a>
|
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</span>
|
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</td>
|
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</tr>
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</tbody>
|
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group ">
|
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<a href="/clinicalSynopsis/268800" 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>
|
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</div>
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<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/268800" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/268800" 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>
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<div>
|
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<p />
|
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</div>
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
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<div class="small" style="margin: 5px">
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<div>
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<div>
|
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<span class="h5 mim-font">
|
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<strong> Muscle </strong>
|
|
</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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|
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- Infantile muscle weakness<br /> - Muscle wasting <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/88092000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">88092000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0541794&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0541794</a>, <a href="https://bioportal.bioontology.org/search?q=C0026846&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026846</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003202" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003202</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003202" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003202</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> Neuro </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Startle reaction <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038186&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038186</a>]</span><br /> - Progressive mental and motor deterioration <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1856565&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1856565</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007272" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007272</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007272" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007272</a>]</span><br /> - Cerebellar ataxia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/85102008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">85102008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0007758&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007758</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>]</span><br /> - Dysarthria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8011004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8011004</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.13" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.13</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/784.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">784.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span><br /> - Fasciculations <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/82470000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">82470000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R25.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R25.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0015644&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015644</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002380" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002380</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002380" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002380</a>]</span><br /> - Pyramidal tract dysfunction <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1504405&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1504405</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002493" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002493</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002493" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002493</a>]</span><br /> - Hyperreflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/86854008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">86854008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151889&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151889</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001347</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001347</a>]</span><br /> - Impaired thermal sensitivity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4021222&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4021222</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010829" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010829</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010829" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010829</a>]</span><br /> - Orthostatic hypotension <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/28651003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">28651003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I95.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I95.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/458.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">458.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020651&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020651</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001278" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001278</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001278" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001278</a>]</span><br /> - Postural dizziness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/103017008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">103017008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/407645004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">407645004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234987&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234987</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> Cranium </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Macrocephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/12138000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">12138000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1145403003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1145403003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q75.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q75.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221355&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221355</a>, <a href="https://bioportal.bioontology.org/search?q=C2243051&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2243051</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000256" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000256</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001355" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001355</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000256" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000256</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=dd989bb153739761147ef05dc870b050" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Macrocephaly-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=dd989bb153739761147ef05dc870b050" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></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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<span class="h5 mim-font">
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<strong> Facies </strong>
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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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- Doll-like face<br /> - Coarse facies <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1845847&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1845847</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000280</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000280</a>]</span><br />
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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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<span class="h5 mim-font">
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<strong> Eyes </strong>
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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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- Early blindness<br /> - Cherry red spots<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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<span class="h5 mim-font">
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<strong> Tongue </strong>
|
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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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- Macroglossia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/25273001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">25273001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/270516002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">270516002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K14.8" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K14.8</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q38.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q38.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/750.15" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">750.15</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0024421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0024421</a>, <a href="https://bioportal.bioontology.org/search?q=C0009677&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009677</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000158" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000158</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000158" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000158</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=ac5acf24e74116d49a4df85084887155" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Tongue,Large-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=ac5acf24e74116d49a4df85084887155" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></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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<span class="h5 mim-font">
|
|
<strong> Cardiac </strong>
|
|
</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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|
- Cardiomegaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8186001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8186001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I51.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I51.7</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/429.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">429.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018800&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018800</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001640" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001640</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001640" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001640</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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<span class="h5 mim-font">
|
|
<strong> Skel </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- High lumbar gibbus<br />
|
|
|
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</span>
|
|
</div>
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</div>
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|
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<div>
|
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<div>
|
|
<span class="h5 mim-font">
|
|
<strong> GI </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Chronic diarrhea <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/236071009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">236071009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0401151&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0401151</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002028" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002028</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002028" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002028</a>]</span><br /> - Episodic abdominal pain <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3808022&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3808022</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002574" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002574</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002574" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002574</a>]</span><br /> - Hepatosplenomegaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/36760000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">36760000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019214&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019214</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001433" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001433</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001433" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001433</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>
|
|
<span class="h5 mim-font">
|
|
<strong> Skin </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Impaired sweating <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4479296&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4479296</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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<span class="h5 mim-font">
|
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<strong> GU </strong>
|
|
</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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|
- Impotence <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/860914002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">860914002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N52.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N52.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/N52" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N52</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/F52.21" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F52.21</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2187990&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2187990</a>, <a href="https://bioportal.bioontology.org/search?q=C0242350&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0242350</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100639</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0000802" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000802</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000802" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000802</a>]</span><br /> - Mild urinary incontinence <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/165232002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">165232002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R32" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R32</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/788.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">788.30</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/788.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">788.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042024&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042024</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000020" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000020</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000020" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000020</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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<span class="h5 mim-font">
|
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<strong> Misc </strong>
|
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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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- Lethal usually by age 3 years<br /> - Intolerance to heat<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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<span class="h5 mim-font">
|
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<strong> Lab </strong>
|
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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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- Hexosaminidase B beta chain deficiency<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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<span class="h5 mim-font">
|
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<strong> Inheritance </strong>
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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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- Autosomal recessive with multiple alleles and compounds<br />
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</span>
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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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<p>A number sign (#) is used with this entry because Sandhoff disease is caused by mutation in the beta subunit of hexosaminidase (HEXB; <a href="/entry/606873">606873</a>) on chromosome 5q13.</p>
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<p>Sandhoff disease is a progressive neurodegenerative disorder characterized by an accumulation of GM2 gangliosides, particularly in neurons, and is clinically indistinguishable from Tay-Sachs disease (<a href="/entry/272800">272800</a>).</p>
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<p><a href="#39" class="mim-tip-reference" title="Sandhoff, K., Andreae, U., Jatzkewitz, H. <strong>Deficient hexosaminidase activity in an exceptional case of Tay-Sachs disease with additional storage of kidney globoside in visceral organs.</strong> Life Sci. 7: 283-288, 1968.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5651108/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5651108</a>] [<a href="https://doi.org/10.1016/0024-3205(68)90024-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5651108">Sandhoff et al. (1968)</a> gave the initial description of the disorder that bears his name. <a href="#30" class="mim-tip-reference" title="O'Brien, J. S. <strong>Ganglioside storage diseases. In: Harris, H.; Hirschhorn, K. (eds.): Advances in Human Genetics. Vol. 3.</strong> New York: Plenum Press (pub.) 1971. Pp. 39-98."None>O'Brien (1971)</a> studied 2 Mexican-American sisters and a boy of Anglo-Saxon extraction. Most patients have been non-Jewish; however, the clinical and pathologic picture is very similar to Tay-Sachs disease (<a href="/entry/272800">272800</a>). Weakness begins in the first 6 months of life. Startle reaction, early blindness, progressive mental and motor deterioration, doll-like face, cherry red spots, and macrocephaly are all present as in Tay-Sachs disease. Death usually occurs by age 3 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5651108" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In the case reported by <a href="#20" class="mim-tip-reference" title="Krivit, W., Desnick, R. J., Lee, J., Moller, J., Wright, F., Sweeley, C. C., Snyder, P. D., Jr., Sharp, H. L. <strong>Generalized accumulation of neutral glycosphingolipids with G(m2) ganglioside accumulation in the brain. Sandhoff's disease (variant of Tay-Sachs disease).</strong> Am. J. Med. 52: 763-770, 1972.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5030173/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5030173</a>] [<a href="https://doi.org/10.1016/0002-9343(72)90082-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5030173">Krivit et al. (1972)</a>, signs of heart involvement preceded those of nervous system change. A pansystolic murmur and cardiomegaly were discovered at 3 months. Neurologic deterioration was first noted at 8 months. Coarse facies, macroglossia, megalencephaly, minimal hepatosplenomegaly and high lumbar gibbus suggested Hurler syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5030173" 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="#8" class="mim-tip-reference" title="Der Kaloustian, V. M., Khoury, M. J., Hallal, R., Idriss, Z. H., Deeb, M. E., Wakid, N. W., Haddad, F. S. <strong>Sandhoff disease: a prevalent form of infantile Gm2 gangliosidosis in Lebanon.</strong> Am. J. Hum. Genet. 33: 85-89, 1981.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7468596/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7468596</a>]" pmid="7468596">Der Kaloustian et al. (1981)</a> described 7 cases in Lebanon. The largest collection of cases is represented by the 36 patients in 15 families described in a Creole population of Argentina (<a href="#9" class="mim-tip-reference" title="Dodelson de Kremer, R., Boldini, C. D., Capra, A. P., Levstein, I. M., Bainttein, N., Hidalgo, P. K., Hliba, H. <strong>Sandhoff disease: 36 cases from Cordoba, Argentina.</strong> J. Inherit. Metab. Dis. 8: 46, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3157833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3157833</a>] [<a href="https://doi.org/10.1007/BF01805485" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3157833">Dodelson de Kremer et al., 1985</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7468596+3157833" 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="#11" class="mim-tip-reference" title="Frey, L. C., Ringel, S. P., Filley, C. M. <strong>The natural history of cognitive dysfunction in late-onset GM2 gangliosidosis.</strong> Arch. Neurol. 62: 989-994, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15956171/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15956171</a>] [<a href="https://doi.org/10.1001/archneur.62.6.989" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15956171">Frey et al. (2005)</a> reported 3 adult patients, including 2 sisters, with late-onset GM2-gangliosidosis diagnosed in childhood. All had learning difficulties in school, and all had been hospitalized for either emotional lability, intermittent psychosis, or confusional state. As adults, neurologic evaluations showed variable features of muscle weakness, muscle atrophy, fasciculations, supranuclear gaze palsy, muscular atrophy, hyperreflexia, and extensor plantar responses. Serial neuropsychologic examination in 1 of the 2 sisters showed significant declines in cognitive and executive function over 10 years. In a literature review of 62 patients, <a href="#11" class="mim-tip-reference" title="Frey, L. C., Ringel, S. P., Filley, C. M. <strong>The natural history of cognitive dysfunction in late-onset GM2 gangliosidosis.</strong> Arch. Neurol. 62: 989-994, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15956171/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15956171</a>] [<a href="https://doi.org/10.1001/archneur.62.6.989" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15956171">Frey et al. (2005)</a> found that 44% had some degree of cognitive dysfunction, 62% of whom showed progressive dementia. Cerebellar and cortical atrophy were common. <a href="#11" class="mim-tip-reference" title="Frey, L. C., Ringel, S. P., Filley, C. M. <strong>The natural history of cognitive dysfunction in late-onset GM2 gangliosidosis.</strong> Arch. Neurol. 62: 989-994, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15956171/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15956171</a>] [<a href="https://doi.org/10.1001/archneur.62.6.989" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15956171">Frey et al. (2005)</a> concluded that patients with late-onset GM2 gangliosidosis have a high risk of dementia, and that patients with dementia often have other neurologic manifestations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15956171" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#43" class="mim-tip-reference" title="Santoro, M., Modoni, A., Sabatelli, M., Madia, F., Piemonte, F., Tozzi, G., Ricci, E., Tonali, P. A., Silvestri, G. <strong>Chronic GM2 gangliosidosis type Sandhoff associated with a novel missense HEXB gene mutation causing a double pathogenic effect.</strong> Molec. Genet. Metab. 91: 111-114, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17251047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17251047</a>] [<a href="https://doi.org/10.1016/j.ymgme.2006.12.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17251047">Santoro et al. (2007)</a> reported 2 sibs, aged 62 and 48 years, with the chronic, late-onset form of GM2 gangliosidosis. Both sibs had symptom onset in the fifth decade of life and had wasting and weakness of proximal limb muscles, absent deep tendon reflexes, and dysarthria. One sib became nonambulatory at age 60, and the other had an abnormal gait at age 48. EMG and nerve conduction studies showed a sensory axonal neuropathy, and brain MRI showed mild cerebellar atrophy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17251047" 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="#44" class="mim-tip-reference" title="Spence, M. W., Ripley, B. A., Embil, J. A., Tibbles, A. R. <strong>A new variant of Sandhoff's disease.</strong> Pediat. Res. 8: 628-637, 1974.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4134664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4134664</a>] [<a href="https://doi.org/10.1203/00006450-197406000-00003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4134664">Spence et al. (1974)</a> described a case of clinically, histologically, and chemically typical Sandhoff disease in a black male. Total hexosaminidase activity in the blood was 20 to 24% of normal (compared with the usual value of less than 5%), whereas in the liver the level was less than 2% of normal. This may be an allelic variant of Sandhoff disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4134664" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 10-year-old male with progressive cerebellar ataxia and psychomotor retardation, <a href="#48" class="mim-tip-reference" title="Wood, S., MacDougall, B. G. <strong>Juvenile Sandhoff disease: some properties of the residual hexosaminidase in cultured fibroblasts.</strong> Am. J. Hum. Genet. 28: 489-495, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10724</a>]" pmid="10724">Wood and MacDougall (1976)</a> found almost complete absence of total hexosaminidase activity in serum, leukocytes, and cultured skin fibroblasts. In spite of disparate clinical findings, this disorder may be allelic to the classic infantile form of Sandhoff disease in view of the similarity of the enzyme deficiency. Studies of residual hexosaminidase isozymes in the juvenile and infantile forms suggested that the defects may be different allelic modifications of the beta subunit common to Hex-A and Hex-B (<a href="#48" class="mim-tip-reference" title="Wood, S., MacDougall, B. G. <strong>Juvenile Sandhoff disease: some properties of the residual hexosaminidase in cultured fibroblasts.</strong> Am. J. Hum. Genet. 28: 489-495, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10724</a>]" pmid="10724">Wood and MacDougall, 1976</a>). <a href="#49" class="mim-tip-reference" title="Wood, S. <strong>Juvenile Sandhoff disease: complementation tests with Sandhoff and Tay-Sachs disease using polyethylene glycol-induced cell fusion.</strong> Hum. Genet. 41: 325-329, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/417993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">417993</a>] [<a href="https://doi.org/10.1007/BF00284766" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="417993">Wood (1978)</a> found no complementation of Sandhoff and juvenile Sandhoff cells, suggesting allelism. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=417993+10724" 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="#17" class="mim-tip-reference" title="Johnson, W. G., Chutorian, A. M. <strong>Inheritance of the enzyme defect in a new hexosaminidase deficiency disease.</strong> Ann. Neurol. 4: 399-403, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/104655/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">104655</a>] [<a href="https://doi.org/10.1002/ana.410040503" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="104655">Johnson and Chutorian (1978)</a> found a new form of hexosaminidase deficiency characterized clinically by mild, juvenile-onset, slowly progressive cerebellar ataxia, and macular cherry red spots. Hexosaminidase B appeared to be absent, resulting in a relative increase in Hex-A in screening tests. They suggested that this condition may be due to a mutation allelic to that for Sandhoff disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=104655" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In one of its mutant forms, Hex-A deficiency can lead to late-onset, progressive motor neuron disease. <a href="#5" class="mim-tip-reference" title="Cashman, N. R., Antel, J. P., Hancock, L. W., Dawson, G., Horwitz, A. L., Johnson, W. G., Huttenlocher, P. R., Wollmann, R. L. <strong>N-acetyl-beta-hexosaminidase beta locus defect and juvenile motor neuron disease: a case study.</strong> Ann. Neurol. 19: 568-572, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3014997/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3014997</a>] [<a href="https://doi.org/10.1002/ana.410190608" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3014997">Cashman et al. (1986)</a> presented a case demonstrating that the same is true for Hex-B deficiency. Their female patient had a progressive motor neuron syndrome that began at age 7 years and was characterized by dysarthria, muscle wasting, fasciculations, and pyramidal tract dysfunction. Rectal biopsy at age 24 showed membranous cytoplasmic bodies in submucosal ganglion cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3014997" 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="Lowden, J. A., Ives, E. J., Keene, D. L., Burton, A. L., Skomorowski, M. A., Howard, F. <strong>Carrier detection in Sandhoff disease.</strong> Am. J. Hum. Genet. 30: 38-45, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/414620/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">414620</a>]" pmid="414620">Lowden et al. (1978)</a> described Sandhoff disease in a Metis kindred of northern Saskatchewan and discussed carrier detection. <a href="#6" class="mim-tip-reference" title="Chamoles, N. A., Blanco, M., Gaggioli, D., Casentini, C. <strong>Tay-Sachs and Sandhoff diseases: enzymatic diagnosis in dried blood spots on filter paper: retrospective diagnoses in newborn-screening cards.</strong> Clin. Chim. Acta 318: 133-137, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11880123/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11880123</a>] [<a href="https://doi.org/10.1016/s0009-8981(02)00002-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11880123">Chamoles et al. (2002)</a> described methods for enzymatic detection of Tay-Sachs and Sandhoff disease in newborns using dried blood spots on filter paper. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=414620+11880123" 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>Differential Diagnosis</em></strong></p><p>
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<a href="#18" class="mim-tip-reference" title="Kaback, M. M. <strong>Personal Communication.</strong> Torrance, Calif. 10/11/1985."None>Kaback (1985)</a> knew of no case of Sandhoff disease in a Jewish child. It may be that the rare cases are confused with Tay-Sachs disease; however, the hepatosplenomegaly should distinguish them as it did in Sandhoff's original case.</p>
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<p>Tay-Sachs disease (<a href="/entry/272800">272800</a>) results from a mutation in the alpha subunit (HEXA; <a href="/entry/606869">606869</a>) of the hexosaminidase A enzyme, and Sandhoff disease results from mutation in the beta subunit (HEXB; <a href="/entry/606873">606873</a>) of the hexosaminidase A and B enzymes. Thus, hexosaminidases A and B are both deficient in Sandhoff disease. <a href="#45" class="mim-tip-reference" title="Srivastava, S. K., Beutler, E. <strong>Hexosaminidase-A and hexosaminidase-B: studies in Tay-Sachs' and Sandhoff's disease.</strong> Nature 241: 463, 1973.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4122341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4122341</a>] [<a href="https://doi.org/10.1038/241463a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4122341">Srivastava and Beutler (1973)</a> maintained that hexosaminidases A and B share a common subunit that is lacking in Sandhoff disease, whereas a subunit unique to hexosaminidase A is deficient in Tay-Sachs disease. <a href="#12" class="mim-tip-reference" title="Galjaard, H., Hoogeveen, A., de Wit-Verbeek, H. A., Rauser, A. J. J., Keijzer, W., Westerveld, A., Bootsma, D. <strong>Tay-Sachs and Sandhoff's disease: intergenic complementation after somatic cell hybridization.</strong> Exp. Cell Res. 87: 444-448, 1974.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4416048/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4416048</a>] [<a href="https://doi.org/10.1016/0014-4827(74)90515-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4416048">Galjaard et al. (1974)</a>, <a href="#47" class="mim-tip-reference" title="Thomas, G. H., Taylor, H. A., Miller, C. S., Axelman, J., Migeon, B. R. <strong>Genetic complementation after fusion of Tay-Sachs and Sandhoff cells.</strong> Nature 250: 580-582, 1974.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4367631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4367631</a>] [<a href="https://doi.org/10.1038/250580a0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4367631">Thomas et al. (1974)</a>, and <a href="#37" class="mim-tip-reference" title="Rattazzi, M. C., Brown, J. A., Davidson, R. G., Shows, T. B. <strong>Tay-Sachs and Sandhoff-Jatzkewitz diseases: complementation of hexosaminidase A deficiency by somatic cell hybridization.</strong> Birth Defects Orig. Art. Ser. XI(3): 232-235, 1975. Note: Alternate: Cytogenet. Cell Genet. 14: 402-405, 1975."None>Rattazzi et al. (1975)</a> showed that Hex-A activity appears after fusion of Tay-Sachs and Sandhoff cells, suggesting genetic complementation. Abnormal radioactive-sulfate kinetics and mucopolysacchariduria are observed in Sandhoff disease but not in Tay-Sachs disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4367631+4122341+4416048" 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>Through serial analysis of gene expression (SAGE), <a href="#27" class="mim-tip-reference" title="Myerowitz, R., Lawson, D., Mizukami, H., Mi, Y., Tifft, C. J., Proia, R. L. <strong>Molecular pathophysiology in Tay-Sachs and Sandhoff diseases as revealed by gene expression profiling.</strong> Hum. Molec. Genet. 11: 1343-1350, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12019216/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12019216</a>] [<a href="https://doi.org/10.1093/hmg/11.11.1343" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12019216">Myerowitz et al. (2002)</a> determined gene expression profiles in cerebral cortex from a Tay-Sachs patient, a Sandhoff disease patient, and a pediatric control. Examination of genes that showed altered expression in both patients revealed molecular details of the pathophysiology of the disorders relating to neuronal dysfunction and loss. A large fraction of the elevated genes in the patients could be attributed to activated macrophages/microglia and astrocytes, and included class II histocompatibility antigens, the proinflammatory cytokine osteopontin (SPP1; <a href="/entry/166490">166490</a>), complement components, proteinases and inhibitors, galectins, osteonectin (SPARC; <a href="/entry/182120">182120</a>), and prostaglandin D2 synthase (PTGDS; <a href="/entry/176803">176803</a>). The authors proposed a model of neurodegeneration that includes inflammation as a factor leading to the precipitous loss of neurons in individuals with these disorders. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12019216" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The HEXB locus (<a href="/entry/606873">606873</a>) has been assigned to chromosome 5 (<a href="#14" class="mim-tip-reference" title="Gilbert, F., Kucherlapati, R. S., Creagan, R. P., Murnane, M. J., Darlington, G. J., Ruddle, F. H. <strong>Tay-Sachs' and Sandhoff's diseases: the assignment of genes for hexosaminidase A and B to individual human chromosomes.</strong> Proc. Nat. Acad. Sci. 72: 263-267, 1975.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1054503/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1054503</a>] [<a href="https://doi.org/10.1073/pnas.72.1.263" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1054503">Gilbert et al., 1975</a>). In a child with a de novo balanced translocation t(5;13)(q11;p11), <a href="#25" class="mim-tip-reference" title="Mattei, J. F., Balestrazzi, P., Baeteman, M. A., Mattei, M. G. <strong>De novo balanced translocation (5;13)(q11;p11) in a child with Franceschetti syndrome and significant decrease of hexosaminidase B. (Abstract)</strong> Cytogenet. Cell Genet. 37: 532, 1984."None>Mattei et al. (1984)</a> found decreased levels of Hex-B, suggesting to these workers that the HEXB gene assignment can be narrowed to 5q11. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1054503" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Chern, C. J., Beutler, E., Kuhl, W., Gilbert, F., Mellman, W. J., Croce, C. M. <strong>Characterization of heteropolymeric hexosaminidase A in human X mouse hybrid cells.</strong> Proc. Nat. Acad. Sci. 73: 3637-3640, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/62363/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">62363</a>] [<a href="https://doi.org/10.1073/pnas.73.10.3637" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="62363">Chern et al. (1976)</a> studied heteropolymeric hexosaminidase A formed by human-mouse hybrid cells that contained an X;15 translocation chromosome but lacked human chromosome 5. Tests with specific antisera suggested that the hybrid molecule had human alpha units and mouse beta units. The findings are consistent with hexosaminidase A being composed of alpha and beta subunits coded by genes on chromosomes 15 and 5, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=62363" 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="#32" class="mim-tip-reference" title="O'Dowd, B. F., Klavins, M. H., Willard, H. F., Gravel, R., Lowden, J. A., Mahuran, D. J. <strong>Molecular heterogeneity in the infantile and juvenile forms of Sandhoff disease (0-variant G(M2) gangliosidosis).</strong> J. Biol. Chem. 261: 12680-12685, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3017984/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3017984</a>]" pmid="3017984">O'Dowd et al. (1986)</a> concluded that the primary gene defect in the majority of Sandhoff cases is in the HEXB gene itself. They studied 5 juvenile cell lines, all of which were found to have normal or reduced levels of pre-beta-chain mRNA and no gross abnormalities in the HEXB gene. Of the 11 infantile type cell lines examined, 4 were found to contain no detectable pre-beta-chain mRNA. Two of the 4 contained partial gene deletions located to the 5-prime end of the HEXB genes. One of these cell lines had previously been assigned to the single complementation group in Sandhoff disease. Thus, the clinical heterogeneity in Sandhoff disease appears to be related to different allelic HEXB mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3017984" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#34" class="mim-tip-reference" title="Oonk, J. G. W., Van der Helm, H. J., Martin, J. J. <strong>Spinocerebellar degeneration: hexosaminidase A and B deficiency in two adult sisters.</strong> Neurology 29: 380-384, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/571983/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">571983</a>] [<a href="https://doi.org/10.1212/wnl.29.3.380" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="571983">Oonk et al. (1979)</a> reported the cases of 2 adult sisters with spinocerebellar degeneration and very low activities of both Hex-A and Hex-B. <a href="#1" class="mim-tip-reference" title="Bolhuis, P. A., Oonk, J. G. W., Kamp, P. E., Ris, A. J., Michalski, J. C., Overdijk, B., Reuser, A. J. J. <strong>Ganglioside storage, hexosaminidase lability, and urinary oligosaccharides in adult Sandhoff's disease.</strong> Neurology 37: 75-81, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2948136/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2948136</a>] [<a href="https://doi.org/10.1212/wnl.37.1.75" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2948136">Bolhuis et al. (1987)</a> reported the autopsy findings of one of the sisters. She had suffered from progressive disabling spinocerebellar disease with motor neuron involvement, but had no dementia, seizures, or ophthalmologic abnormalities. She died of severe urosepsis at age 39. GM2-ganglioside storage was most pronounced in the cerebellum. Only very small amounts of mature beta chain were synthesized. <a href="#1" class="mim-tip-reference" title="Bolhuis, P. A., Oonk, J. G. W., Kamp, P. E., Ris, A. J., Michalski, J. C., Overdijk, B., Reuser, A. J. J. <strong>Ganglioside storage, hexosaminidase lability, and urinary oligosaccharides in adult Sandhoff's disease.</strong> Neurology 37: 75-81, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2948136/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2948136</a>] [<a href="https://doi.org/10.1212/wnl.37.1.75" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2948136">Bolhuis et al. (1987)</a> concluded that the disorder was the result of a 'destabilizing mutation' in the HEXB locus. <a href="#2" class="mim-tip-reference" title="Bolhuis, P. A., Ponne, N. J., Bikker, H., Baas, F., de Jong, J. M. B. V. <strong>Molecular basis of an adult form of Sandhoff disease: substitution of glutamine for arginine at position 505 of the beta-chain of beta-hexosaminidase results in a labile enzyme.</strong> Biochim. Biophys. Acta 1182: 142-146, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8357844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8357844</a>] [<a href="https://doi.org/10.1016/0925-4439(93)90134-m" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8357844">Bolhuis et al. (1993)</a> demonstrated that these 2 sisters were compound heterozygotes for an mRNA-negative allele on 1 chromosome 5 and an R505Q mutation (<a href="/entry/606873#0009">606873.0009</a>) on the homologous chromosome. Transfection of COS cells with a cDNA construct containing the R505Q mutation resulted in the expression of a labile form of beta-hexosaminidase, thus confirming their earlier conclusion. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2948136+8357844+571983" 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="Brown, C. A., McInnes, B., Dodelson de Kremer, R., Mahuran, D. J. <strong>Characterization of two HEXB gene mutations in Argentinian patients with Sandhoff disease.</strong> Biochim. Biophys. Acta 1180: 91-98, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1390948/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1390948</a>] [<a href="https://doi.org/10.1016/0925-4439(92)90031-h" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1390948">Brown et al. (1992)</a> and <a href="#19" class="mim-tip-reference" title="Kleiman, F. E., Dodelson de Kremer, R., Oller de Ramirez, A., Gravel, R. A., Argarana, C. E. <strong>Sandhoff disease in Argentina: high frequency of a splice site mutation in the HEXB gene and correlation between enzyme and DNA-based tests for heterozygote detection.</strong> Hum. Genet. 94: 279-282, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8076944/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8076944</a>] [<a href="https://doi.org/10.1007/BF00208283" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8076944">Kleiman et al. (1994)</a> gave updates on the HEXB mutations in the Argentinian deme described by <a href="#9" class="mim-tip-reference" title="Dodelson de Kremer, R., Boldini, C. D., Capra, A. P., Levstein, I. M., Bainttein, N., Hidalgo, P. K., Hliba, H. <strong>Sandhoff disease: 36 cases from Cordoba, Argentina.</strong> J. Inherit. Metab. Dis. 8: 46, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3157833/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3157833</a>] [<a href="https://doi.org/10.1007/BF01805485" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3157833">Dodelson de Kremer et al. (1985)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3157833+1390948+8076944" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#28" class="mim-tip-reference" title="Neufeld, E. F. <strong>Natural history and inherited disorders of a lysosomal enzyme, beta-hexosaminidase.</strong> J. Biol. Chem. 264: 10927-10930, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2525553/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2525553</a>]" pmid="2525553">Neufeld (1989)</a> provided a review of the disorders related to mutations in the HEXA and HEXB genes. <a href="#24" class="mim-tip-reference" title="Mahuran, D. J. <strong>Personal Communication.</strong> Toronto, Canada 9/17/1998."None>Mahuran (1998)</a> stated that he maintains a database of published hexosaminidase and GM2A (<a href="/entry/613109">613109</a>) mutations and that the database contains 23 HEXB mutations, 86 HEXA (<a href="/entry/606869">606869</a>) mutations, and 4 GM2A mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2525553" 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>Among 12 unrelated Italian patients with Sandhoff disease, 11 of whom had the infantile type, <a href="#51" class="mim-tip-reference" title="Zampieri, S., Filocamo, M., Buratti, E., Stroppiano, M., Vlahovicek, K., Rosso, N., Bignulin, E., Regis, S., Carnevale, F., Bembi, B., Dardis, A. <strong>Molecular and functional analysis of the HEXB gene in Italian patients affected with Sandhoff disease: identification of six novel alleles.</strong> Neurogenetics 10: 49-58, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18758829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18758829</a>] [<a href="https://doi.org/10.1007/s10048-008-0145-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18758829">Zampieri et al. (2009)</a> identified 11 different mutations in the HEXB gene, including 6 novel mutations (see, e.g., <a href="/entry/606873#0017">606873.0017</a> and <a href="/entry/606873#0018">606873.0018</a>). The common 16-kb deletion (<a href="/entry/606873#0001">606873.0001</a>) was not identified in this patient cohort. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18758829" 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="#4" class="mim-tip-reference" title="Cantor, R. M., Kaback, M. M. <strong>Sandhoff disease (SHD) heterozygote frequencies (HF) in North American (NA) Jewish (J) and non-Jewish (NJ) populations: implications for carrier (C) screening (Abstract)</strong> Am. J. Hum. Genet. 37: A48, 1985."None>Cantor and Kaback (1985)</a> stated that the gene frequency for Sandhoff disease was about 1/1000 in Jews and 1/600 in non-Jews.</p><p><a href="#10" class="mim-tip-reference" title="Drousiotou, A., Stylianidou, G., Anastasiadou, V., Christopoulos, G., Mavrikiou, E., Georgiou, T., Kalakoutis, G., Oladimeja, A., Hara, Y., Suzuki, K., Furihata, K., Ueno, I., Ioannou, P. A., Fensom, A. H. <strong>Sandhoff disease in Cyprus: population screening by biochemical and DNA analysis indicates a high frequency of carriers in the Maronite community.</strong> Hum. Genet. 107: 12-17, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10982028/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10982028</a>] [<a href="https://doi.org/10.1007/s004390000324" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10982028">Drousiotou et al. (2000)</a> noted that in the previous 15 years, 4 patients with the infantile form of Sandhoff disease had been identified in 4 different families in Cyprus (population, 703,000; birth rate, 1.7%). Three of these cases came from the Christian Maronite community (less than 1% of the population) and 1 from the Greek community (84% of the population). This relatively large number of patients prompted <a href="#10" class="mim-tip-reference" title="Drousiotou, A., Stylianidou, G., Anastasiadou, V., Christopoulos, G., Mavrikiou, E., Georgiou, T., Kalakoutis, G., Oladimeja, A., Hara, Y., Suzuki, K., Furihata, K., Ueno, I., Ioannou, P. A., Fensom, A. H. <strong>Sandhoff disease in Cyprus: population screening by biochemical and DNA analysis indicates a high frequency of carriers in the Maronite community.</strong> Hum. Genet. 107: 12-17, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10982028/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10982028</a>] [<a href="https://doi.org/10.1007/s004390000324" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10982028">Drousiotou et al. (2000)</a> to initiate an epidemiologic study to establish the frequency of the mutant gene in Cyprus. Measuring beta-hexosaminidases A and B in both leukocytes and serum, they identified 35 carriers among 244 random Maronite samples and 15 among 28 Maronites with a family history of Sandhoff disease, but only 1 carrier out of 115 random samples from the Greek community. Of 50 Maronite carriers examined, 42 were found to have deletion of adenine at nucleotide 76 (<a href="/entry/606873#0016">606873.0016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10982028" 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="#42" class="mim-tip-reference" title="Sango, K., Yamanaka, S., Hoffmann, A., Okuda, Y., Grinberg, A., Westphal, H., McDonald, M. P., Crawley, J. N., Sandhoff, K., Suzuki, K., Proia, R. L. <strong>Mouse models of Tay-Sachs and Sandhoff diseases differ in neurologic phenotype and ganglioside metabolism.</strong> Nature Genet. 11: 170-176, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7550345/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7550345</a>] [<a href="https://doi.org/10.1038/ng1095-170" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7550345">Sango et al. (1995)</a> found that mice generated through disruption of the HEXB gene have severe neurologic involvement, representing a satisfactory model of Sandhoff disease. In contrast, disruption of the HEXA gene with the intent of producing a model of Tay-Sachs disease resulted in no neurologic abnormality, although the mice exhibited biochemical and pathologic features of the disease. Differences in the ganglioside degradative pathway between mice and humans were revealed by the studies. <a href="#35" class="mim-tip-reference" title="Phaneuf, D., Wakamatsu, N., Huang, J.-Q., Borowski, A., Peterson, A. C., Fortunato, S. R., Ritter, G., Igdoura, S. A., Morales, C. R., Benoit, G., Akerman, B. R., Leclerc, D., Hanai, N., Marth, J. D., Trasler, J. M., Gravel, R. A. <strong>Dramatically different phenotypes in mouse models of human Tay-Sachs and Sandhoff disease.</strong> Hum. Molec. Genet. 5: 1-14, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8789434/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8789434</a>] [<a href="https://doi.org/10.1093/hmg/5.1.1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8789434">Phaneuf et al. (1996)</a> likewise found that mice with disruption of the Hexa gene suffered no obvious behavioral or neurologic deficit while those homozygous for a disruption of the Hexb gene developed a fatal neurodegenerative disease, with spasticity, muscle weakness, rigidity, tremor, and ataxia. They proposed that homozygous Hexa deficient mice escaped disease through particle catabolism of accumulated GM2 via GA2 through the combined action of sialidase and beta-hexosaminidase B. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8789434+7550345" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Huang, J.-Q., Trasler, J. M., Igdoura, S., Michaud, J., Hanai, N., Gravel, R. A. <strong>Apoptotic cell death in mouse models of GM2 gangliosidosis and observations on human Tay-Sachs and Sandhoff diseases.</strong> Hum. Molec. Genet. 6: 1879-1885, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9302266/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9302266</a>] [<a href="https://doi.org/10.1093/hmg/6.11.1879" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9302266">Huang et al. (1997)</a> found that neuron death in HEXB-/- mice is associated with apoptosis occurring throughout the central nervous system, while HEXA-/- mice were minimally involved at the same age. Studies of autopsy samples of brain and spinal cord from human Tay-Sachs and Sandhoff diseases revealed apoptosis in both instances, in keeping with the severe expression of both diseases. <a href="#15" class="mim-tip-reference" title="Huang, J.-Q., Trasler, J. M., Igdoura, S., Michaud, J., Hanai, N., Gravel, R. A. <strong>Apoptotic cell death in mouse models of GM2 gangliosidosis and observations on human Tay-Sachs and Sandhoff diseases.</strong> Hum. Molec. Genet. 6: 1879-1885, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9302266/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9302266</a>] [<a href="https://doi.org/10.1093/hmg/6.11.1879" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9302266">Huang et al. (1997)</a> suggested that neuron death is caused by unscheduled apoptosis, implicating accumulated GM2 ganglioside or a derivative in triggering of the apoptotic cascade. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9302266" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>The mucopolysaccharidosis phenotype is not seen in patients with either Tay-Sachs disease or Sandhoff disease and is also not seen in the knockout mice that have been created as a model of these 2 disorders by homozygosity for a defect in either HEXA or HEXB. However, double knockout mice lacking both subunits of lysosomal beta-hexosaminidase were found by <a href="#41" class="mim-tip-reference" title="Sango, K., McDonald, M. P., Crawley, J. N., Mack, M. L., Tifft, C. J., Skop, E., Starr, C. M., Hoffmann, A., Sandhoff, K., Suzuki, K., Proia, R. L. <strong>Mice lacking both subunits of lysosomal beta-hexosaminidase display gangliosidosis and mucopolysaccharidosis.</strong> Nature Genet. 14: 348-352, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8896570/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8896570</a>] [<a href="https://doi.org/10.1038/ng1196-348" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8896570">Sango et al. (1996)</a> to display both gangliosidosis and mucopolysaccharidosis. Lack of mucopolysaccharide storage in Tay-Sachs and Sandhoff diseases is presumably due to functional redundancy in the beta-hexosaminidase enzyme system. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8896570" 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="Liu, Y., Wada, R., Kawai, H., Sango, K., Deng, C., Tai, T., McDonald, M. P., Araujo, K., Crawley, J. N., Bierfreund, U., Sandhoff, K., Suzuki, K., Proia, R. L. <strong>A genetic model of substrate deprivation therapy for a glycosphingolipid storage disorder.</strong> J. Clin. Invest. 103: 497-505, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10021458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10021458</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10021458[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/10.1172/JCI5542" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10021458">Liu et al. (1999)</a> explored a new treatment paradigm for glycosphingolipid storage disorders, namely substrate depletion therapy, by constructing a genetic model in mice. Sandhoff disease mice, which abnormally accumulate glycosphingolipids, were bred with mice that were blocked in their synthesis of GSLs. The mice with simultaneous defects in GSL synthesis and degradation no longer accumulated GSLs, had improved neurologic function, and had a much longer life span; however, these mice eventually developed a late-onset neurologic disease because of accumulation of another class of substrate, oligosaccharides. The results supported the validity of substrate deprivation therapy, but also highlighted limitations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10021458" 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 possible therapeutic strategy for treating Sandhoff disease and related disorders is substrate deprivation. This would utilize an inhibitor of glycosphingolipid biosynthesis to balance synthesis with the impaired rate of catabolism, thus preventing storage. One such inhibitor is N-butyldeoxynojirimycin, which had been in clinical trials for the potential treatment of type I Gaucher disease (<a href="/entry/230800">230800</a>), a related disorder that involves glycosphingolipid storage in peripheral tissues but not in the central nervous system. It had also been used in the treatment of Tay-Sachs disease in mice (<a href="#36" class="mim-tip-reference" title="Platt, F. M., Neises, G. R., Reinkensmeier, G., Townsend, M. J., Perry, V. H., Proia, R. L., Winchester, B., Dwek, R. A., Butters, T. D. <strong>Prevention of lysosomal storage in Tay-Sachs mice treated with N-butyldeoxynojirimycin.</strong> Science 276: 428-431, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9103204/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9103204</a>] [<a href="https://doi.org/10.1126/science.276.5311.428" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9103204">Platt et al., 1997</a>). <a href="#16" class="mim-tip-reference" title="Jeyakumar, M., Butters, T. D., Cortina-Borja, M., Hunnam, V., Proia, R. L., Perry, V. H., Dwek, R. A., Platt, F. M. <strong>Delayed symptom onset and increased life expectancy in Sandhoff disease mice treated with N-butyldeoxynojirimycin.</strong> Proc. Nat. Acad. Sci. 96: 6388-6393, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10339597/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10339597</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10339597[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/10.1073/pnas.96.11.6388" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10339597">Jeyakumar et al. (1999)</a> evaluated whether this drug could also be applied to the treatment of diseases for central nervous system storage and pathology. They found that in the mouse model of Sandhoff disease there was delay of symptom onset, reduced storage in the brain and peripheral tissues, and increased life expectancy. Substrate deprivation therefore offered a potentially general therapy for this family of lysosomal storage diseases, including those with central nervous system disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9103204+10339597" 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="#50" class="mim-tip-reference" title="Yamaguchi, A., Katsuyama, K., Nagahama, K., Takai, T., Aoki, I., Yamanaka, S. <strong>Possible role of autoantibodies in the pathophysiology of GM2 gangliosidoses.</strong> J. Clin. Invest. 113: 200-208, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14722612/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14722612</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=14722612[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/10.1172/JCI19639" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="14722612">Yamaguchi et al. (2004)</a> found that the progressive neurologic disease induced in Hexb -/- mice, the animal model for Sandhoff disease, was associated with the appearance of antiganglioside autoantibodies. Both elevation of serum antiganglioside autoantibodies and IgG deposition to CNS neurons were found in the advanced stages of the disease in Hexb -/- mice; serum transfer from these mice showed IgG binding to neurons. To determine the role of these autoantibodies, the Fc receptor gamma gene (FCER1G; <a href="/entry/147139">147139</a>) was additionally disrupted in Hexb -/- mice, as it plays a key role in immune complex-mediated autoimmune diseases. Clinical symptoms were improved and life spans were extended in the double-null mice; the number of apoptotic cells was also decreased. The level of ganglioside accumulation, however, did not change. IgG deposition was also confirmed in the brain of an autopsied Sandhoff disease patient. Taken together, these findings suggested that the production of autoantibodies plays an important role in the pathogenesis of neuropathy in Sandhoff disease and therefore provides a target for therapy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14722612" 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="#George1978" class="mim-tip-reference" title="George, D. L., Francke, U. <strong>Evidence for localization of the gene for hexosaminidase B to the cen-q13 region of human chromosome 5 using mouse-human hybrid cells.</strong> Cytogenet. Cell Genet. 22: 408-411, 1978.">George and Francke (1978)</a>; <a href="#MacLeod1977" class="mim-tip-reference" title="MacLeod, P. M., Wood, S., Jan, J. E., Applegarth, D. A., Dolman, C. L. <strong>Progressive cerebellar ataxia, spasticity, psychomotor retardation, and hexosaminidase deficiency in a 10-year-old child: juvenile Sandhoff disease.</strong> Neurology 27: 571-573, 1977.">MacLeod et al. (1977)</a>; <a href="#Messer1980" class="mim-tip-reference" title="Messer, G., Harel, S., Erlich, B., Navon, R., Nemet, P., Sarnat, H., Shomrat, R., Legum, C. <strong>Ultrastructure of the conjunctiva, skin, and gingiva: a case of Sandhoff's disease in a Jewish patient.</strong> Arch. Path. Lab. Med. 104: 123-129, 1980.">Messer et al.
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(1980)</a>; <a href="#Neuwelt1985" class="mim-tip-reference" title="Neuwelt, E. A., Johnson, W. G., Blank, N. K., Pagel, M. A., Maslen-McClure, C., McClure, M. J., Wu, P. M. <strong>Characterization of a new model of G(M2)-gangliosidosis (Sandhoff's disease) in Korat cats.</strong> J. Clin. Invest. 76: 482-490, 1985.">Neuwelt et al. (1985)</a>; <a href="#O'Brien1978" class="mim-tip-reference" title="O'Brien, J. S. <strong>Suggestions for a nomenclature for the GM2 gangliosidoses making certain (possibly unwarranted) assumptions. (Comments)</strong> Am. J. Hum. Genet. 30: 672-675, 1978.">O'Brien (1978)</a>; <a href="#Okada1972" class="mim-tip-reference" title="Okada, S., McCrea, M., O'Brien, J. S. <strong>Sandhoff's disease (Gm2 gangliosidosis type 2): clinical, chemical, and enzyme studies in five patients.</strong> Pediat. Res. 6: 606-615, 1972.">Okada et al. (1972)</a>; <a href="#Rubin1988" class="mim-tip-reference" title="Rubin, M., Karpati, G., Wolfe, L. S., Carpenter, S., Klavins, M. H., Mahuran, D. J. <strong>Adult onset motor neuronopathy in the juvenile type of hexosaminidase A and B deficiency.</strong> J. Neurol. Sci. 87: 103-119, 1988.">Rubin et al. (1988)</a>; <a href="#Sandhoff1971" class="mim-tip-reference" title="Sandhoff, K., Harzer, K., Wassle, W., Jatzkewitz, H. <strong>Enzyme alterations and lipid storage in three variants of Tay-Sachs disease.</strong> J. Neurochem. 18: 2469-2489, 1971.">Sandhoff et al. (1971)</a>; <a href="#Suzuki1973" class="mim-tip-reference" title="Suzuki, Y., Koizumi, Y., Togari, H., Ogawam, Y. <strong>Sandhoff disease: diagnosis of heterozygous carriers.</strong> Clin. Chim. Acta 48: 153-158, 1973.">Suzuki et al. (1973)</a>
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<strong>Ganglioside storage, hexosaminidase lability, and urinary oligosaccharides in adult Sandhoff's disease.</strong>
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Neurology 37: 75-81, 1987.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2948136/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2948136</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2948136" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<strong>Molecular basis of an adult form of Sandhoff disease: substitution of glutamine for arginine at position 505 of the beta-chain of beta-hexosaminidase results in a labile enzyme.</strong>
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Biochim. Biophys. Acta 1182: 142-146, 1993.
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[<a href="https://doi.org/10.1016/0925-4439(93)90134-m" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0925-4439(92)90031-h" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ana.410190608" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0009-8981(02)00002-5" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.73.10.3637" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF01805485" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/s004390000324" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1001/archneur.62.6.989" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0014-4827(74)90515-1" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1159/000130984" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.72.1.263" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/hmg/6.11.1879" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ana.410040503" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00208283" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5651108/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5651108</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5651108" 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/10.1016/0024-3205(68)90024-6" target="_blank">Full Text</a>]
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<a id="Sandhoff1971" class="mim-anchor"></a>
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<strong>Enzyme alterations and lipid storage in three variants of Tay-Sachs disease.</strong>
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[<a href="https://doi.org/10.1111/j.1471-4159.1971.tb00204.x" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/ng1196-348" target="_blank">Full Text</a>]
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<a id="Sango1995" class="mim-anchor"></a>
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Sango, K., Yamanaka, S., Hoffmann, A., Okuda, Y., Grinberg, A., Westphal, H., McDonald, M. P., Crawley, J. N., Sandhoff, K., Suzuki, K., Proia, R. L.
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[<a href="https://doi.org/10.1038/ng1095-170" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17251047/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17251047</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17251047" 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/10.1016/j.ymgme.2006.12.004" target="_blank">Full Text</a>]
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<a id="Spence1974" class="mim-anchor"></a>
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[<a href="https://doi.org/10.1203/00006450-197406000-00003" target="_blank">Full Text</a>]
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<a id="Srivastava1973" class="mim-anchor"></a>
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Srivastava, S. K., Beutler, E.
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<strong>Hexosaminidase-A and hexosaminidase-B: studies in Tay-Sachs' and Sandhoff's disease.</strong>
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Nature 241: 463, 1973.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4122341/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4122341</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4122341" 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/10.1038/241463a0" target="_blank">Full Text</a>]
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<a id="Suzuki1973" class="mim-anchor"></a>
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Suzuki, Y., Koizumi, Y., Togari, H., Ogawam, Y.
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<strong>Sandhoff disease: diagnosis of heterozygous carriers.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4758879/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4758879</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4758879" 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/10.1016/0009-8981(73)90360-4" target="_blank">Full Text</a>]
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<a id="Thomas1974" class="mim-anchor"></a>
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<strong>Genetic complementation after fusion of Tay-Sachs and Sandhoff cells.</strong>
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Nature 250: 580-582, 1974.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4367631/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4367631</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4367631" 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/10.1038/250580a0" target="_blank">Full Text</a>]
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Wood, S., MacDougall, B. G.
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<strong>Juvenile Sandhoff disease: some properties of the residual hexosaminidase in cultured fibroblasts.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10724/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10724</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10724" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Wood1978" class="mim-anchor"></a>
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<strong>Juvenile Sandhoff disease: complementation tests with Sandhoff and Tay-Sachs disease using polyethylene glycol-induced cell fusion.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/417993/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">417993</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=417993" 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/10.1007/BF00284766" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1172/JCI19639" target="_blank">Full Text</a>]
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Zampieri, S., Filocamo, M., Buratti, E., Stroppiano, M., Vlahovicek, K., Rosso, N., Bignulin, E., Regis, S., Carnevale, F., Bembi, B., Dardis, A.
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<strong>Molecular and functional analysis of the HEXB gene in Italian patients affected with Sandhoff disease: identification of six novel alleles.</strong>
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Neurogenetics 10: 49-58, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18758829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18758829</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18758829" 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/10.1007/s10048-008-0145-1" target="_blank">Full Text</a>]
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Hilary J. Vernon - updated : 12/14/2021
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Cassandra L. Kniffin - updated : 3/25/2009<br>Cassandra L. Kniffin - updated : 9/1/2005<br>Victor A. McKusick - updated : 2/10/2004<br>George E. Tiller - updated : 2/24/2003<br>Cassandra L. Kniffin - reorganized : 5/7/2002<br>Cassandra L. Kniffin - updated : 5/7/2002<br>Victor A. McKusick - updated : 9/12/2000<br>Ada Hamosh - updated : 3/14/2000<br>Victor A. McKusick - updated : 7/14/1999<br>Victor A. McKusick - updated : 3/16/1999<br>Victor A. McKusick - updated : 1/25/1999<br>Victor A. McKusick - updated : 1/12/1999<br>Victor A. McKusick - updated : 8/13/1998<br>Perseveranda M. Cagas - updated : 11/6/1996
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Victor A. McKusick : 6/4/1986
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carol : 10/14/2016<br>joanna : 12/03/2013<br>carol : 11/4/2009<br>wwang : 4/10/2009<br>ckniffin : 3/25/2009<br>carol : 10/1/2007<br>terry : 10/12/2005<br>wwang : 9/19/2005<br>ckniffin : 9/1/2005<br>carol : 7/1/2004<br>tkritzer : 2/13/2004<br>terry : 2/10/2004<br>cwells : 2/24/2003<br>carol : 5/7/2002<br>ckniffin : 5/7/2002<br>carol : 5/7/2002<br>ckniffin : 5/6/2002<br>carol : 9/14/2000<br>terry : 9/12/2000<br>alopez : 3/20/2000<br>terry : 3/14/2000<br>mgross : 7/19/1999<br>terry : 7/14/1999<br>terry : 6/9/1999<br>terry : 3/16/1999<br>carol : 2/1/1999<br>terry : 1/25/1999<br>carol : 1/14/1999<br>terry : 1/12/1999<br>dkim : 9/21/1998<br>alopez : 9/16/1998<br>alopez : 9/16/1998<br>terry : 9/14/1998<br>carol : 8/17/1998<br>terry : 8/13/1998<br>terry : 7/31/1998<br>terry : 6/4/1998<br>joanna : 5/14/1998<br>dholmes : 1/26/1998<br>alopez : 1/13/1998<br>alopez : 1/12/1998<br>dholmes : 1/6/1998<br>mark : 6/10/1997<br>mark : 12/26/1996<br>mark : 11/6/1996<br>terry : 10/31/1996<br>terry : 10/29/1996<br>mark : 2/14/1996<br>terry : 2/8/1996<br>mark : 12/5/1995<br>mark : 10/6/1995<br>terry : 7/10/1995<br>davew : 6/7/1994<br>warfield : 4/20/1994<br>mimadm : 4/14/1994<br>carol : 11/17/1993
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<span class="mim-font">
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<strong>#</strong> 268800
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SANDHOFF DISEASE
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<em>Alternative titles; symbols</em>
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<h4>
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GM2-GANGLIOSIDOSIS, TYPE II<br />
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HEXOSAMINIDASES A AND B DEFICIENCY
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Other entities represented in this entry:
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SANDHOFF DISEASE, ADULT TYPE, INCLUDED
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SANDHOFF DISEASE, JUVENILE TYPE, INCLUDED<br />
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SANDHOFF DISEASE, INFANTILE TYPE, INCLUDED
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<strong>SNOMEDCT:</strong> 23849003;
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<strong>ICD10CM:</strong> E75.01;
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<strong>ORPHA:</strong> 309155, 309162, 309169, 796;
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<strong>DO:</strong> 3323;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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<span class="mim-font">
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5q13.3
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Sandhoff disease, infantile, juvenile, and adult forms
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268800
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Autosomal recessive
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<span class="mim-font">
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3
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HEXB
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606873
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because Sandhoff disease is caused by mutation in the beta subunit of hexosaminidase (HEXB; 606873) on chromosome 5q13.</p>
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<strong>Description</strong>
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<p>Sandhoff disease is a progressive neurodegenerative disorder characterized by an accumulation of GM2 gangliosides, particularly in neurons, and is clinically indistinguishable from Tay-Sachs disease (272800).</p>
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<strong>Clinical Features</strong>
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<p>Sandhoff et al. (1968) gave the initial description of the disorder that bears his name. O'Brien (1971) studied 2 Mexican-American sisters and a boy of Anglo-Saxon extraction. Most patients have been non-Jewish; however, the clinical and pathologic picture is very similar to Tay-Sachs disease (272800). Weakness begins in the first 6 months of life. Startle reaction, early blindness, progressive mental and motor deterioration, doll-like face, cherry red spots, and macrocephaly are all present as in Tay-Sachs disease. Death usually occurs by age 3 years. </p><p>In the case reported by Krivit et al. (1972), signs of heart involvement preceded those of nervous system change. A pansystolic murmur and cardiomegaly were discovered at 3 months. Neurologic deterioration was first noted at 8 months. Coarse facies, macroglossia, megalencephaly, minimal hepatosplenomegaly and high lumbar gibbus suggested Hurler syndrome. </p><p>Der Kaloustian et al. (1981) described 7 cases in Lebanon. The largest collection of cases is represented by the 36 patients in 15 families described in a Creole population of Argentina (Dodelson de Kremer et al., 1985). </p><p>Frey et al. (2005) reported 3 adult patients, including 2 sisters, with late-onset GM2-gangliosidosis diagnosed in childhood. All had learning difficulties in school, and all had been hospitalized for either emotional lability, intermittent psychosis, or confusional state. As adults, neurologic evaluations showed variable features of muscle weakness, muscle atrophy, fasciculations, supranuclear gaze palsy, muscular atrophy, hyperreflexia, and extensor plantar responses. Serial neuropsychologic examination in 1 of the 2 sisters showed significant declines in cognitive and executive function over 10 years. In a literature review of 62 patients, Frey et al. (2005) found that 44% had some degree of cognitive dysfunction, 62% of whom showed progressive dementia. Cerebellar and cortical atrophy were common. Frey et al. (2005) concluded that patients with late-onset GM2 gangliosidosis have a high risk of dementia, and that patients with dementia often have other neurologic manifestations. </p><p>Santoro et al. (2007) reported 2 sibs, aged 62 and 48 years, with the chronic, late-onset form of GM2 gangliosidosis. Both sibs had symptom onset in the fifth decade of life and had wasting and weakness of proximal limb muscles, absent deep tendon reflexes, and dysarthria. One sib became nonambulatory at age 60, and the other had an abnormal gait at age 48. EMG and nerve conduction studies showed a sensory axonal neuropathy, and brain MRI showed mild cerebellar atrophy. </p>
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<strong>Heterogeneity</strong>
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<p><strong><em>Clinical Heterogeneity</em></strong></p><p>
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Spence et al. (1974) described a case of clinically, histologically, and chemically typical Sandhoff disease in a black male. Total hexosaminidase activity in the blood was 20 to 24% of normal (compared with the usual value of less than 5%), whereas in the liver the level was less than 2% of normal. This may be an allelic variant of Sandhoff disease. </p><p>In a 10-year-old male with progressive cerebellar ataxia and psychomotor retardation, Wood and MacDougall (1976) found almost complete absence of total hexosaminidase activity in serum, leukocytes, and cultured skin fibroblasts. In spite of disparate clinical findings, this disorder may be allelic to the classic infantile form of Sandhoff disease in view of the similarity of the enzyme deficiency. Studies of residual hexosaminidase isozymes in the juvenile and infantile forms suggested that the defects may be different allelic modifications of the beta subunit common to Hex-A and Hex-B (Wood and MacDougall, 1976). Wood (1978) found no complementation of Sandhoff and juvenile Sandhoff cells, suggesting allelism. </p><p>Johnson and Chutorian (1978) found a new form of hexosaminidase deficiency characterized clinically by mild, juvenile-onset, slowly progressive cerebellar ataxia, and macular cherry red spots. Hexosaminidase B appeared to be absent, resulting in a relative increase in Hex-A in screening tests. They suggested that this condition may be due to a mutation allelic to that for Sandhoff disease. </p><p>In one of its mutant forms, Hex-A deficiency can lead to late-onset, progressive motor neuron disease. Cashman et al. (1986) presented a case demonstrating that the same is true for Hex-B deficiency. Their female patient had a progressive motor neuron syndrome that began at age 7 years and was characterized by dysarthria, muscle wasting, fasciculations, and pyramidal tract dysfunction. Rectal biopsy at age 24 showed membranous cytoplasmic bodies in submucosal ganglion cells. </p>
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<strong>Diagnosis</strong>
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<p>Lowden et al. (1978) described Sandhoff disease in a Metis kindred of northern Saskatchewan and discussed carrier detection. Chamoles et al. (2002) described methods for enzymatic detection of Tay-Sachs and Sandhoff disease in newborns using dried blood spots on filter paper. </p><p><strong><em>Differential Diagnosis</em></strong></p><p>
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Kaback (1985) knew of no case of Sandhoff disease in a Jewish child. It may be that the rare cases are confused with Tay-Sachs disease; however, the hepatosplenomegaly should distinguish them as it did in Sandhoff's original case.</p>
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<strong>Pathogenesis</strong>
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<p>Tay-Sachs disease (272800) results from a mutation in the alpha subunit (HEXA; 606869) of the hexosaminidase A enzyme, and Sandhoff disease results from mutation in the beta subunit (HEXB; 606873) of the hexosaminidase A and B enzymes. Thus, hexosaminidases A and B are both deficient in Sandhoff disease. Srivastava and Beutler (1973) maintained that hexosaminidases A and B share a common subunit that is lacking in Sandhoff disease, whereas a subunit unique to hexosaminidase A is deficient in Tay-Sachs disease. Galjaard et al. (1974), Thomas et al. (1974), and Rattazzi et al. (1975) showed that Hex-A activity appears after fusion of Tay-Sachs and Sandhoff cells, suggesting genetic complementation. Abnormal radioactive-sulfate kinetics and mucopolysacchariduria are observed in Sandhoff disease but not in Tay-Sachs disease. </p><p>Through serial analysis of gene expression (SAGE), Myerowitz et al. (2002) determined gene expression profiles in cerebral cortex from a Tay-Sachs patient, a Sandhoff disease patient, and a pediatric control. Examination of genes that showed altered expression in both patients revealed molecular details of the pathophysiology of the disorders relating to neuronal dysfunction and loss. A large fraction of the elevated genes in the patients could be attributed to activated macrophages/microglia and astrocytes, and included class II histocompatibility antigens, the proinflammatory cytokine osteopontin (SPP1; 166490), complement components, proteinases and inhibitors, galectins, osteonectin (SPARC; 182120), and prostaglandin D2 synthase (PTGDS; 176803). The authors proposed a model of neurodegeneration that includes inflammation as a factor leading to the precipitous loss of neurons in individuals with these disorders. </p>
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<strong>Mapping</strong>
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<p>The HEXB locus (606873) has been assigned to chromosome 5 (Gilbert et al., 1975). In a child with a de novo balanced translocation t(5;13)(q11;p11), Mattei et al. (1984) found decreased levels of Hex-B, suggesting to these workers that the HEXB gene assignment can be narrowed to 5q11. </p><p>Chern et al. (1976) studied heteropolymeric hexosaminidase A formed by human-mouse hybrid cells that contained an X;15 translocation chromosome but lacked human chromosome 5. Tests with specific antisera suggested that the hybrid molecule had human alpha units and mouse beta units. The findings are consistent with hexosaminidase A being composed of alpha and beta subunits coded by genes on chromosomes 15 and 5, respectively. </p>
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<strong>Molecular Genetics</strong>
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<p>O'Dowd et al. (1986) concluded that the primary gene defect in the majority of Sandhoff cases is in the HEXB gene itself. They studied 5 juvenile cell lines, all of which were found to have normal or reduced levels of pre-beta-chain mRNA and no gross abnormalities in the HEXB gene. Of the 11 infantile type cell lines examined, 4 were found to contain no detectable pre-beta-chain mRNA. Two of the 4 contained partial gene deletions located to the 5-prime end of the HEXB genes. One of these cell lines had previously been assigned to the single complementation group in Sandhoff disease. Thus, the clinical heterogeneity in Sandhoff disease appears to be related to different allelic HEXB mutations. </p><p>Oonk et al. (1979) reported the cases of 2 adult sisters with spinocerebellar degeneration and very low activities of both Hex-A and Hex-B. Bolhuis et al. (1987) reported the autopsy findings of one of the sisters. She had suffered from progressive disabling spinocerebellar disease with motor neuron involvement, but had no dementia, seizures, or ophthalmologic abnormalities. She died of severe urosepsis at age 39. GM2-ganglioside storage was most pronounced in the cerebellum. Only very small amounts of mature beta chain were synthesized. Bolhuis et al. (1987) concluded that the disorder was the result of a 'destabilizing mutation' in the HEXB locus. Bolhuis et al. (1993) demonstrated that these 2 sisters were compound heterozygotes for an mRNA-negative allele on 1 chromosome 5 and an R505Q mutation (606873.0009) on the homologous chromosome. Transfection of COS cells with a cDNA construct containing the R505Q mutation resulted in the expression of a labile form of beta-hexosaminidase, thus confirming their earlier conclusion. </p><p>Brown et al. (1992) and Kleiman et al. (1994) gave updates on the HEXB mutations in the Argentinian deme described by Dodelson de Kremer et al. (1985). </p><p>Neufeld (1989) provided a review of the disorders related to mutations in the HEXA and HEXB genes. Mahuran (1998) stated that he maintains a database of published hexosaminidase and GM2A (613109) mutations and that the database contains 23 HEXB mutations, 86 HEXA (606869) mutations, and 4 GM2A mutations. </p><p>Among 12 unrelated Italian patients with Sandhoff disease, 11 of whom had the infantile type, Zampieri et al. (2009) identified 11 different mutations in the HEXB gene, including 6 novel mutations (see, e.g., 606873.0017 and 606873.0018). The common 16-kb deletion (606873.0001) was not identified in this patient cohort. </p>
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<strong>Population Genetics</strong>
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<p>Cantor and Kaback (1985) stated that the gene frequency for Sandhoff disease was about 1/1000 in Jews and 1/600 in non-Jews.</p><p>Drousiotou et al. (2000) noted that in the previous 15 years, 4 patients with the infantile form of Sandhoff disease had been identified in 4 different families in Cyprus (population, 703,000; birth rate, 1.7%). Three of these cases came from the Christian Maronite community (less than 1% of the population) and 1 from the Greek community (84% of the population). This relatively large number of patients prompted Drousiotou et al. (2000) to initiate an epidemiologic study to establish the frequency of the mutant gene in Cyprus. Measuring beta-hexosaminidases A and B in both leukocytes and serum, they identified 35 carriers among 244 random Maronite samples and 15 among 28 Maronites with a family history of Sandhoff disease, but only 1 carrier out of 115 random samples from the Greek community. Of 50 Maronite carriers examined, 42 were found to have deletion of adenine at nucleotide 76 (606873.0016). </p>
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<strong>Animal Model</strong>
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<p>Sango et al. (1995) found that mice generated through disruption of the HEXB gene have severe neurologic involvement, representing a satisfactory model of Sandhoff disease. In contrast, disruption of the HEXA gene with the intent of producing a model of Tay-Sachs disease resulted in no neurologic abnormality, although the mice exhibited biochemical and pathologic features of the disease. Differences in the ganglioside degradative pathway between mice and humans were revealed by the studies. Phaneuf et al. (1996) likewise found that mice with disruption of the Hexa gene suffered no obvious behavioral or neurologic deficit while those homozygous for a disruption of the Hexb gene developed a fatal neurodegenerative disease, with spasticity, muscle weakness, rigidity, tremor, and ataxia. They proposed that homozygous Hexa deficient mice escaped disease through particle catabolism of accumulated GM2 via GA2 through the combined action of sialidase and beta-hexosaminidase B. </p><p>Huang et al. (1997) found that neuron death in HEXB-/- mice is associated with apoptosis occurring throughout the central nervous system, while HEXA-/- mice were minimally involved at the same age. Studies of autopsy samples of brain and spinal cord from human Tay-Sachs and Sandhoff diseases revealed apoptosis in both instances, in keeping with the severe expression of both diseases. Huang et al. (1997) suggested that neuron death is caused by unscheduled apoptosis, implicating accumulated GM2 ganglioside or a derivative in triggering of the apoptotic cascade. </p><p>The mucopolysaccharidosis phenotype is not seen in patients with either Tay-Sachs disease or Sandhoff disease and is also not seen in the knockout mice that have been created as a model of these 2 disorders by homozygosity for a defect in either HEXA or HEXB. However, double knockout mice lacking both subunits of lysosomal beta-hexosaminidase were found by Sango et al. (1996) to display both gangliosidosis and mucopolysaccharidosis. Lack of mucopolysaccharide storage in Tay-Sachs and Sandhoff diseases is presumably due to functional redundancy in the beta-hexosaminidase enzyme system. </p><p>Liu et al. (1999) explored a new treatment paradigm for glycosphingolipid storage disorders, namely substrate depletion therapy, by constructing a genetic model in mice. Sandhoff disease mice, which abnormally accumulate glycosphingolipids, were bred with mice that were blocked in their synthesis of GSLs. The mice with simultaneous defects in GSL synthesis and degradation no longer accumulated GSLs, had improved neurologic function, and had a much longer life span; however, these mice eventually developed a late-onset neurologic disease because of accumulation of another class of substrate, oligosaccharides. The results supported the validity of substrate deprivation therapy, but also highlighted limitations. </p><p>A possible therapeutic strategy for treating Sandhoff disease and related disorders is substrate deprivation. This would utilize an inhibitor of glycosphingolipid biosynthesis to balance synthesis with the impaired rate of catabolism, thus preventing storage. One such inhibitor is N-butyldeoxynojirimycin, which had been in clinical trials for the potential treatment of type I Gaucher disease (230800), a related disorder that involves glycosphingolipid storage in peripheral tissues but not in the central nervous system. It had also been used in the treatment of Tay-Sachs disease in mice (Platt et al., 1997). Jeyakumar et al. (1999) evaluated whether this drug could also be applied to the treatment of diseases for central nervous system storage and pathology. They found that in the mouse model of Sandhoff disease there was delay of symptom onset, reduced storage in the brain and peripheral tissues, and increased life expectancy. Substrate deprivation therefore offered a potentially general therapy for this family of lysosomal storage diseases, including those with central nervous system disease. </p><p>Yamaguchi et al. (2004) found that the progressive neurologic disease induced in Hexb -/- mice, the animal model for Sandhoff disease, was associated with the appearance of antiganglioside autoantibodies. Both elevation of serum antiganglioside autoantibodies and IgG deposition to CNS neurons were found in the advanced stages of the disease in Hexb -/- mice; serum transfer from these mice showed IgG binding to neurons. To determine the role of these autoantibodies, the Fc receptor gamma gene (FCER1G; 147139) was additionally disrupted in Hexb -/- mice, as it plays a key role in immune complex-mediated autoimmune diseases. Clinical symptoms were improved and life spans were extended in the double-null mice; the number of apoptotic cells was also decreased. The level of ganglioside accumulation, however, did not change. IgG deposition was also confirmed in the brain of an autopsied Sandhoff disease patient. Taken together, these findings suggested that the production of autoantibodies plays an important role in the pathogenesis of neuropathy in Sandhoff disease and therefore provides a target for therapy. </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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<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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George and Francke (1978); MacLeod et al. (1977); Messer et al.
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(1980); Neuwelt et al. (1985); O'Brien (1978); Okada et al. (1972);
|
|
Rubin et al. (1988); Sandhoff et al. (1971); Suzuki et al. (1973)
|
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</span>
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<div>
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<br />
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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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