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Entry
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- #606812 - FUMARASE DEFICIENCY; FMRD
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- OMIM
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<p>
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<span class="h4">#606812</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<li role="presentation">
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<a href="/clinicalSynopsis/606812"><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="#inheritance">Inheritance</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="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div style="display: table-cell;">External Links</div>
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</a>
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</h4>
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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=FUMARASE DEFICIENCY" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=3376&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1506/" 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/2963" 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/fumarase-deficiency" 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=606812[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=24" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/69a6140d-e66e-41f2-8b62-a1d11171761f/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/disease/DOID:0111261" 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/606812" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0111261" 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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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 237983002<br />
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<strong>ORPHA:</strong> 24<br />
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<strong>DO:</strong> 0111261<br />
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">ICD+</a>
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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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606812
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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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FUMARASE DEFICIENCY; FMRD
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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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FUMARIC ACIDURIA
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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="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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<tbody>
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<td>
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<span class="mim-font">
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<a href="/geneMap/1/1836?start=-3&limit=10&highlight=1836">
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1q43
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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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Fumarase deficiency
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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/606812"> 606812 </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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</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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</td>
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<td>
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<span class="mim-font">
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FH
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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/136850"> 136850 </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/606812" 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')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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</div>
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<div class="btn-group">
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
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</button>
|
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<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/606812" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/606812" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<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> 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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<div>
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<span class="mim-font">
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- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
|
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<span class="h5 mim-font">
|
|
<strong> GROWTH </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
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|
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<div>
|
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<div>
|
|
<span class="h5 mim-font">
|
|
<em> Other </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Failure to thrive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/432788009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">432788009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/54840006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">54840006</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0015544&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015544</a>, <a href="https://bioportal.bioontology.org/search?q=C2315100&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2315100</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span><br />
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|
</span>
|
|
</div>
|
|
</div>
|
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|
|
</div>
|
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|
|
</div>
|
|
|
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|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Head </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Macrocephaly, relative <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/3961000119101" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">3961000119101</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849075&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849075</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004482" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004482</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004482" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004482</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> <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 />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Face </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Frontal bossing <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/90145001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">90145001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221354&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221354</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002007</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=3ab8802347404fb5ebf087fa6440bb25" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Frontal_Bossing-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=3ab8802347404fb5ebf087fa6440bb25" 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 />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Eyes </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Hypertelorism <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22006008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22006008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q75.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q75.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/376.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">376.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020534&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020534</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000316" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000316</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000316" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000316</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=593a4d488f00bb03351a0ddffaf4ac9a" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Eyes,Widely_Spaced-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=593a4d488f00bb03351a0ddffaf4ac9a" 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 /> -
|
|
Optic pallor <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2675976&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2675976</a>]</span><br /> -
|
|
Optic atrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/76976005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">76976005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.2</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.20</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/377.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.10</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/377.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0029124&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029124</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</a>]</span><br /> -
|
|
Visual impairment <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246635007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246635007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/7973008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">7973008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/397540003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">397540003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042798&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042798</a>, <a href="https://bioportal.bioontology.org/search?q=C3665347&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3665347</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000505" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000505</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000505" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000505</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Nose </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Depressed nasal bridge <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836542&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836542</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005280</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005280" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005280</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=7043769fd21a78a413fd758918cdda17" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Nasal_Bridge,Depressed-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=7043769fd21a78a413fd758918cdda17" 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 /> -
|
|
Anteverted nares <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/708670007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">708670007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1840077&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1840077</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000463" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000463</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000463" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000463</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=656ef0aca7742d97c5769f51f0dd56de" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Nares,Anteverted-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=656ef0aca7742d97c5769f51f0dd56de" 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 />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Mouth </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
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|
- High-arched palate <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/27272007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">27272007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q38.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q38.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0240635&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0240635</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000218" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000218</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000218" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000218</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
|
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<span class="h5 mim-font">
|
|
<strong> ABDOMEN </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
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<div>
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<div>
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<span class="h5 mim-font">
|
|
<em> Liver </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
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|
|
- Liver failure <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/59927004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">59927004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K72.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K72.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0085605&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085605</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001399" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001399</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001399" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001399</a>]</span><br /> -
|
|
Cholestasis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/30144000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">30144000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/33688009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">33688009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/197446008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">197446008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K83.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K83.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/576.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">576.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0008370&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0008370</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001396" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001396</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001396" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001396</a>]</span><br /> -
|
|
Hepatic fibrosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/62484002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">62484002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K74.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K74.00</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K74.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K74.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0239946&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239946</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001395" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001395</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001395" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001395</a>]</span><br /> -
|
|
Iron deposition <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/84182002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">84182002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0333596&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0333596</a>]</span><br /> -
|
|
Abnormal swollen mitochondria with flat, haphazardly arranged cristae <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3276832&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3276832</a>]</span><br />
|
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</span>
|
|
</div>
|
|
</div>
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</div>
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</div>
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|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> SKIN, NAILS, & HAIR </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
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|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Skin </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Cutaneous leiomyomata (heterozygote carriers) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1847442&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1847442</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/254767008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">254767008</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007620" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007620</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
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|
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</div>
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</div>
|
|
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|
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|
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|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MUSCLE, SOFT TISSUES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Hypotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398151007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398151007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398152000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398152000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026827&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026827</a>, <a href="https://bioportal.bioontology.org/search?q=C1858120&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858120</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001290</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span><br /> -
|
|
Decreased muscle bulk <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2675977&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2675977</a>]</span><br /> -
|
|
Decreased subcutaneous fat <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248316006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248316006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1857657&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1857657</a>, <a href="https://bioportal.bioontology.org/search?q=C0424631&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424631</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003758" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003758</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003758" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003758</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
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|
|
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|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEUROLOGIC </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Central Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Mental retardation, profound <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/31216003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">31216003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F73" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F73</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020796&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020796</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002187" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002187</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002187" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002187</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/317-319.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">317-319.99</a>]</span><br /> -
|
|
Developmental delay <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248290002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248290002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/224958001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">224958001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F88</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/315.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">315.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0557874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0557874</a>, <a href="https://bioportal.bioontology.org/search?q=C0424605&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424605</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span><br /> -
|
|
No language development <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2677327&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2677327</a>]</span><br /> -
|
|
Cerebral atrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/278849000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">278849000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0235946&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0235946</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002059" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002059</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002059" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002059</a>]</span><br /> -
|
|
Seizures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91175000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91175000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span><br /> -
|
|
Status epilepticus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/230456007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">230456007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038220&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038220</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002133" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002133</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002133" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002133</a>]</span><br /> -
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Hypotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398151007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398151007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398152000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398152000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026827&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026827</a>, <a href="https://bioportal.bioontology.org/search?q=C1858120&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858120</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001290</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span><br /> -
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Most patients do not achieve independent sitting or walking <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2675971&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2675971</a>]</span><br /> -
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Ventricular enlargement <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2675972&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2675972</a>]</span><br /> -
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Polymicrogyria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/4945003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">4945003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0266464&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0266464</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002126" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002126</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002126" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002126</a>]</span><br /> -
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Open operculum <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2675973&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2675973</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100954" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100954</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100954" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100954</a>]</span><br /> -
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Choroid plexus cysts <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/230790004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">230790004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0338597&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0338597</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002190" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002190</a>]</span><br /> -
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Decreased white matter volume <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2675974&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2675974</a>]</span><br /> -
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Angulation of the frontal horns <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2675975&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2675975</a>]</span><br /> -
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Small brainstem <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1842688&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1842688</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002365" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002365</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002365" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002365</a>]</span><br /> -
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Agenesis of the corpus callosum <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/5102002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">5102002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q04.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q04.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0175754&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0175754</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001274" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001274</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001274" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001274</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> METABOLIC FEATURES </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Metabolic acidosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/59455009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">59455009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E87.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E87.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0220981&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0220981</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001942" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001942</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001942" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001942</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> HEMATOLOGY </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Polycythemia, neonatal <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/32984002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">32984002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/P61.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">P61.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/776.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">776.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0272153&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0272153</a>]</span><br /> -
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Coagulopathy in those with liver failure <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3276838&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3276838</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> LABORATORY ABNORMALITIES </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Lactic acidemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/190882007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">190882007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0347959&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0347959</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003128" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003128</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003128" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003128</a>]</span><br /> -
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Pyruvic acidemia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1847440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1847440</a>]</span><br /> -
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Fumaric aciduria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237983002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237983002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0342770&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0342770</a>, <a href="https://bioportal.bioontology.org/search?q=C2936826&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2936826</a>]</span><br /> -
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Fumarase activity (mitochondrial and cytosolic) is decreased <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1847441&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1847441</a>]</span><br /> -
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Increased urinary citric acid cycle intermediates <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3276833&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3276833</a>]</span><br /> -
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Increased urinary fumaric acid <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3276834&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3276834</a>]</span><br /> -
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Increased urinary malic acid <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3276835&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3276835</a>]</span><br /> -
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Increased urinary succinic acid <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3276836&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3276836</a>]</span><br /> -
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Hyperbilirubinemia in those with liver failure <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3276837&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3276837</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MISCELLANEOUS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Allelic to hereditary multiple leiomyoma of skin (see <a href="/entry/150800">150800</a>) and hereditary leiomyomatosis and renal cell cancer (<a href="/entry/150800">150800</a>)<br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MOLECULAR BASIS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Caused by mutation in the fumarate hydratase gene (FH, <a href="/entry/136850#0001">136850.0001</a>)<br />
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</span>
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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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<br />
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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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</h4>
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because fumarase deficiency (FMRD) is caused by homozygous or compound heterozygous mutation in the fumarate hydratase gene (FH; <a href="/entry/136850">136850</a>) on chromosome 1q43.</p><p>Heterozygous mutation in the FH gene can cause hereditary leiomyomatosis and renal cell cancer (HLRCC; <a href="/entry/150800">150800</a>).</p>
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<br />
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<a id="description" class="mim-anchor"></a>
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<p>Fumarase deficiency (FMRD) is a severe autosomal recessive metabolic disorder characterized by early-onset hypotonia, profound psychomotor retardation, and brain abnormalities, such as agenesis of the corpus callosum, gyral defects, and ventriculomegaly. Many patients show neonatal distress, metabolic acidosis, and/or encephalopathy (summary by <a href="#7" class="mim-tip-reference" title="Kerrigan, J. F., Aleck, K. A., Tarby, T. J., Bird, C. R., Heidenreich, R. A. <strong>Fumaric aciduria: clinical and imaging features.</strong> Ann. Neurol. 47: 583-588, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10805328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10805328</a>]" pmid="10805328">Kerrigan et al., 2000</a> and <a href="#8" class="mim-tip-reference" title="Mroch, A. R., Laudenschlager, M., Flanagan, J. D. <strong>Detection of a novel FH whole gene deletion in the propositus leading to subsequent prenatal diagnosis in a sibship with fumarase deficiency.</strong> Am. J. Med. Genet. 158A: 155-158, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22069215/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22069215</a>] [<a href="https://doi.org/10.1002/ajmg.a.34344" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22069215">Mroch et al., 2012</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10805328+22069215" 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="#13" class="mim-tip-reference" title="Zinn, A. B., Kerr, D. S., Hoppel, C. L. <strong>Fumarase deficiency: a new cause of mitochondrial encephalomyopathy.</strong> New Eng. J. Med. 315: 469-475, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3736629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3736629</a>] [<a href="https://doi.org/10.1056/NEJM198608213150801" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3736629">Zinn et al. (1986)</a> reported the case of a male infant with mitochondrial encephalopathy who presented at 1 month of age with failure to thrive, developmental delay, hypotonia, cerebral atrophy, lactic and pyruvic acidemia, and fumaric aciduria. The patient died at 8 months of age. Mitochondria isolated from skeletal muscle showed selective defects in the oxidation of glutamate and succinate, whereas isolated liver mitochondria oxidized these normally. Fumarase activity was virtually absent in mitochondria of both sources. Homogenates of liver and muscle also showed very much reduced fumarase activity, indicating that the cytosolic form of the enzyme was also deficient. Organ differences in intramitochondrial accumulation of fumarase were thought to account for the selective oxidative defects observed in skeletal muscle and not in liver mitochondria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3736629" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#12" class="mim-tip-reference" title="Whelan, D. T., Hill, R. E., McClorry, S. <strong>Fumaric aciduria: a new organic aciduria, associated with mental retardation and speech improvement.</strong> Clin. Chim. Acta 132: 301-308, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6616883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6616883</a>] [<a href="https://doi.org/10.1016/0009-8981(83)90008-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6616883">Whelan et al. (1983)</a> reported isolated fumaric aciduria in 2 adult sibs with mental retardation and speech impairment. The authors attributed the increased urinary excretion to a defect in renal clearance; fumarase activity was not assessed. <a href="#9" class="mim-tip-reference" title="Petrova-Benedict, R., Robinson, B. H., Stacey, T. E., Mistry, J., Chalmers, R. A. <strong>Deficient fumarase activity in an infant with fumaricacidemia and its distribution between the different forms of the enzyme seen on isoelectric focusing.</strong> Am. J. Hum. Genet. 40: 257-266, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3578275/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3578275</a>]" pmid="3578275">Petrova-Benedict et al. (1987)</a> reported a case of fumarase deficiency in a mentally retarded child who presented at 6 months of age with hypotonia, microcephaly, and delayed development. Fumarase was deficient in both the mitochondrial and the cytosolic compartments, but the cytosolic enzyme appeared to be more severely affected. <a href="#11" class="mim-tip-reference" title="Snodgrass, P. J. <strong>Fumarase deficiency. (Letter)</strong> New Eng. J. Med. 316: 345 only, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3807970/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3807970</a>]" pmid="3807970">Snodgrass (1987)</a> commented on the occurrence of mild hyperammonemia in fumarase deficiency. <a href="#5" class="mim-tip-reference" title="Gellera, C., Uziel, G., Rimoldi, M., Zeviani, M., Laverda, A., Carrara, F., DiDonato, S. <strong>Fumarase deficiency is an autosomal recessive encephalopathy affecting both the mitochondrial and the cytosolic enzymes.</strong> Neurology 40: 495-499, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2314594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2314594</a>] [<a href="https://doi.org/10.1212/wnl.40.3_part_1.495" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2314594">Gellera et al. (1990)</a> described the clinical features of fumarase deficiency. A 7-month old boy died in a demented state after a clinical course characterized by generalized seizures, psychomotor deterioration, and fumaric aciduria. Marked deficiency of both mitochondrial and cytosolic fumarases was found in skeletal muscle, brain, cerebellum, heart, kidney, liver, and cultured fibroblasts. Anti-fumarase crossreacting material was present in negligible amounts in these tissues. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3578275+2314594+3807970+6616883" 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="Kerrigan, J. F., Aleck, K. A., Tarby, T. J., Bird, C. R., Heidenreich, R. A. <strong>Fumaric aciduria: clinical and imaging features.</strong> Ann. Neurol. 47: 583-588, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10805328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10805328</a>]" pmid="10805328">Kerrigan et al. (2000)</a> reported the clinical features of 8 affected members of a large consanguineous family with fumarase deficiency living in an isolated community in the southwestern United States. The ages of the patients ranged from 20 months to 12 years. All patients were profoundly developmentally retarded and had no language development. Only 1 child had achieved independent walking; all the others were unable to sit. All patients had relative macrocephaly and ventricular enlargement. Other common features included hypotonia, seizures, and status epilepticus. Dysmorphic features included frontal bossing, hypertelorism, depressed nasal bridge, anteverted nares, and high-arched palate. Five of 8 had polycythemia at birth. Neuroimaging showed striking abnormalities of the brain, including polymicrogyria, angulation of the frontal horns, decreased periventricular white matter, and small brainstem. Four patients had optic nerve hypoplasia or pallor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10805328" 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="Mroch, A. R., Laudenschlager, M., Flanagan, J. D. <strong>Detection of a novel FH whole gene deletion in the propositus leading to subsequent prenatal diagnosis in a sibship with fumarase deficiency.</strong> Am. J. Med. Genet. 158A: 155-158, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22069215/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22069215</a>] [<a href="https://doi.org/10.1002/ajmg.a.34344" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22069215">Mroch et al. (2012)</a> reported 2 brothers, born of unrelated parents, with genetically confirmed FH deficiency resulting in death in infancy. The first boy was born prematurely from a pregnancy complicated by polyhydramnios, and showed hypotonia and respiratory insufficiency after birth. An ultrasound at 20 weeks' gestation had shown agenesis of the corpus callosum, ventriculomegaly, bilateral renal pyelectasis, and a ventriculoseptal defect. Postmortem imaging showed lissencephaly. He developed severe metabolic acidosis, necrotizing enterocolitis, liver failure associated with coagulopathy and hyperbilirubinemia, and encephalopathy, resulting in death at age 22 days. Biochemical studies showed increased urinary tyrosine metabolites, citric cycle intermediates, citrulline, fumaric, malic, and succinic acids, and skin biopsy showed fumarase deficiency. Postmortem examination showed a distended abdomen, and the liver showed intrahepatic bile stasis. Electron microscopy of the liver revealed multiple swollen mitochondria with flat, plate-like, haphazardly arranged cristae. Genetic analysis identified compound heterozygosity for mutations in the FH gene: a point mutation (P174R; <a href="/entry/136850#0010">136850.0010</a>) and a whole gene deletion (<a href="/entry/136850#0011">136850.0011</a>). Prenatal diagnosis confirming the deficiency was performed on the subsequent pregnancy by genetic testing of amniocytes. Ultrasound at 20 weeks' gestation showed ventriculomegaly, dangling choroid plexus, and possible agenesis of the corpus callosum. The parents elected to continue with the pregnancy, but the infant died on day 26. Postmortem examination again showed hepatic involvement, with fibrosis, iron deposition, and bile stasis. Electron microscopy showed abnormal mitochondria similar to that observed in his affected brother. Each unaffected parent was heterozygous for one of the mutations, and neither showed cancer or abnormal cutaneous findings suggesting HLRCC. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22069215" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Prasad, C., Napier, M. P., Rupar, C. A., Prasad, C. <strong>Fumarase deficiency: a rare disorder on the crossroads of clinical and metabolic genetics, neurology and cancer.</strong> Clin. Dysmorph. 26: 117-120, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27541980/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27541980</a>] [<a href="https://doi.org/10.1097/MCD.0000000000000148" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27541980">Prasad et al. (2017)</a> reported 2 sisters with an attenuated form of FMRD, including absence of encephalopathy and near-normal urine fumaric acid levels. At age 2.5 years, the older sib was evaluated for failure to thrive and developmental delays. She had a history of constipation and required a gastrostomy tube for feeding issues. She had facial dysmorphisms, including microcephaly, epicanthal folds, bilateral strabismus, low-set ears, a broad nasal bridge, and a tented upper lip. Neurologic examination showed mild ataxia and hypotonia. Before the age of 10 years, she developed focal seizures with secondary generalization. At age 10, she was reported to have appropriate development but unusual behaviors including putting objects in her mouth and causing self-injury. The younger sib was reported to have developmental delay, feeding issues, and dysmorphisms similar to her sister. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27541980" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Grocott, O., Phanor, S. K., Fung, F., Thibert, R. L., Berkmen, M. B. <strong>Clinical report and biochemical analysis of a patient with fumarate hydratase deficiency.</strong> Am. J. Med. Genet. 182A: 504-507, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31746132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31746132</a>] [<a href="https://doi.org/10.1002/ajmg.a.61415" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31746132">Grocott et al. (2020)</a> reported a patient who was diagnosed with dysphagia, gastrointestinal reflux, and poor weight gain at 18 months of age. At 21 months of age she was nonverbal and could not sit or crawl. Urine organic acid analysis demonstrated increased fumaric acid. She developed myoclonic jerks at 3 years of age, and tonic-clonic seizures at 5 years of age. Seizures persisted despite treatment with multiple antiepileptics. At 12 years of age she had seizures, constipation, developmental delay, truncal hypotonia, joint pain, muscle contractures, and scoliosis. She was nonverbal and nonambulatory. Seizure frequency was decreased after lacosamide was added to her therapeutic regimen. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31746132" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In the case reported by <a href="#9" class="mim-tip-reference" title="Petrova-Benedict, R., Robinson, B. H., Stacey, T. E., Mistry, J., Chalmers, R. A. <strong>Deficient fumarase activity in an infant with fumaricacidemia and its distribution between the different forms of the enzyme seen on isoelectric focusing.</strong> Am. J. Hum. Genet. 40: 257-266, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3578275/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3578275</a>]" pmid="3578275">Petrova-Benedict et al. (1987)</a>, the parents of the affected child were first cousins, supporting autosomal recessive inheritance. In the case reported by <a href="#5" class="mim-tip-reference" title="Gellera, C., Uziel, G., Rimoldi, M., Zeviani, M., Laverda, A., Carrara, F., DiDonato, S. <strong>Fumarase deficiency is an autosomal recessive encephalopathy affecting both the mitochondrial and the cytosolic enzymes.</strong> Neurology 40: 495-499, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2314594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2314594</a>] [<a href="https://doi.org/10.1212/wnl.40.3_part_1.495" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2314594">Gellera et al. (1990)</a>, autosomal recessive inheritance was supported by the finding of fumarase activities 30 to 50% of normal in both mitochondria and cytosol from cultured fibroblasts of the parents. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3578275+2314594" 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="#3" class="mim-tip-reference" title="Coughlin, E. M., Chalmers, R. A., Slaugenhaupt, S. A., Gusella, J. F., Shih, V. E., Ramesh, V. <strong>Identification of a molecular defect in a fumarase deficient patient and mapping of the fumarase gene. (Abstract)</strong> Am. J. Hum. Genet. 53 (suppl.): A896 only, 1993."None>Coughlin et al. (1993)</a> identified a homozygous mutation in the FH gene (<a href="/entry/136850#0001">136850.0001</a>) in a patient with fumarase deficiency. Bourgeron et al. (<a href="#2" class="mim-tip-reference" title="Bourgeron, T., Chretien, D., Rotig, A., Munnich, A., Landrieu, P., Rustin, P. <strong>Molecular characterization of fumarase deficiency in two children with progressive encephalopathy. (Abstract)</strong> Am. J. Hum. Genet. 53 (suppl.): A891 only, 1993."None>1993</a>, <a href="#1" class="mim-tip-reference" title="Bourgeron, T., Chretien, D., Poggi-Bach, J., Doonan, S., Rabier, D., Letouze, P., Munnich, A., Rotig, A., Landrieu, P., Rustin, P. <strong>Mutation of the fumarase gene in two siblings with progressive encephalopathy and fumarase deficiency.</strong> J. Clin. Invest. 93: 2514-2518, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8200987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8200987</a>] [<a href="https://doi.org/10.1172/JCI117261" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8200987">1994</a>) identified a homozygous mutation in the FH gene (<a href="/entry/136850#0002">136850.0002</a>) in 2 patients with progressive encephalopathy associated with fumarase deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8200987" 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 2 brothers with infantile-lethal fumarase deficiency, <a href="#8" class="mim-tip-reference" title="Mroch, A. R., Laudenschlager, M., Flanagan, J. D. <strong>Detection of a novel FH whole gene deletion in the propositus leading to subsequent prenatal diagnosis in a sibship with fumarase deficiency.</strong> Am. J. Med. Genet. 158A: 155-158, 2012.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22069215/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22069215</a>] [<a href="https://doi.org/10.1002/ajmg.a.34344" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22069215">Mroch et al. (2012)</a> identified compound heterozygous mutations in the FH gene (<a href="/entry/136850#0010">136850.0010</a>-<a href="/entry/136850#0011">136850.0011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22069215" 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 2 sisters with an attenuated form of FMRD, <a href="#10" class="mim-tip-reference" title="Prasad, C., Napier, M. P., Rupar, C. A., Prasad, C. <strong>Fumarase deficiency: a rare disorder on the crossroads of clinical and metabolic genetics, neurology and cancer.</strong> Clin. Dysmorph. 26: 117-120, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27541980/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27541980</a>] [<a href="https://doi.org/10.1097/MCD.0000000000000148" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="27541980">Prasad et al. (2017)</a> identified compound heterozygous mutations in the FH gene: a duplication (K477dup; <a href="/entry/136850#0012">136850.0012</a>) and a splice site mutation (<a href="/entry/136850#0013">136850.0013</a>). The sibs had no encephalopathy and near-normal urine fumaric acid levels. The mutations segregated with the disorder in the family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27541980" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with FMRD, <a href="#6" class="mim-tip-reference" title="Grocott, O., Phanor, S. K., Fung, F., Thibert, R. L., Berkmen, M. B. <strong>Clinical report and biochemical analysis of a patient with fumarate hydratase deficiency.</strong> Am. J. Med. Genet. 182A: 504-507, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31746132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31746132</a>] [<a href="https://doi.org/10.1002/ajmg.a.61415" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31746132">Grocott et al. (2020)</a> identified compound heterozygous mutations in the FH gene (D65G, <a href="/entry/136850#0014">136850.0014</a>; c.1293delA, <a href="/entry/136850#0015">136850.0015</a>). Fumarase enzyme was purified from plasmids containing FH with each of the patient's mutations. Fumarase with the c.1293delA mutation had defective enzyme activity and oligomerization. Fumarase with the D65G mutation had a lower catalytic activity compared to wildtype. Urine organic acids in the patient demonstrated elevated fumaric acid, and cytosolic and mitochondrial fumarase enzyme activity were decreased in patient fibroblasts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31746132" 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>There is an unusually high incidence of fumarase deficiency in the southwestern United States among members of the Fundamentalist Church of Jesus Christ of Latter Day Saints, a religious community that practices inbreeding and polygamy. The genetic defect was traced to one of the community's founding patriarchs, the late Joseph Smith Jessop, and the first of his plural wives, who had 14 children together (<a href="#4" class="mim-tip-reference" title="Dougherty, J. <strong>Forbidden fruit: inbreeding among polygamists along the Arizona-Utah border is producing a caste of severely retarded and deformed children.</strong> Phoenix New Times, December 29, 2005."None>Dougherty, 2005</a>).</p>
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<a id="Bourgeron1994" class="mim-anchor"></a>
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Bourgeron, T., Chretien, D., Poggi-Bach, J., Doonan, S., Rabier, D., Letouze, P., Munnich, A., Rotig, A., Landrieu, P., Rustin, P.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8200987/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8200987</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8200987" 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/10.1172/JCI117261" target="_blank">Full Text</a>]
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Bourgeron, T., Chretien, D., Rotig, A., Munnich, A., Landrieu, P., Rustin, P.
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<strong>Molecular characterization of fumarase deficiency in two children with progressive encephalopathy. (Abstract)</strong>
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Am. J. Hum. Genet. 53 (suppl.): A891 only, 1993.
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Coughlin, E. M., Chalmers, R. A., Slaugenhaupt, S. A., Gusella, J. F., Shih, V. E., Ramesh, V.
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<strong>Identification of a molecular defect in a fumarase deficient patient and mapping of the fumarase gene. (Abstract)</strong>
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Am. J. Hum. Genet. 53 (suppl.): A896 only, 1993.
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Dougherty, J.
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<strong>Forbidden fruit: inbreeding among polygamists along the Arizona-Utah border is producing a caste of severely retarded and deformed children.</strong>
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Phoenix New Times, December 29, 2005.
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Gellera, C., Uziel, G., Rimoldi, M., Zeviani, M., Laverda, A., Carrara, F., DiDonato, S.
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<strong>Fumarase deficiency is an autosomal recessive encephalopathy affecting both the mitochondrial and the cytosolic enzymes.</strong>
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Neurology 40: 495-499, 1990.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2314594/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2314594</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2314594" 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/10.1212/wnl.40.3_part_1.495" target="_blank">Full Text</a>]
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Grocott, O., Phanor, S. K., Fung, F., Thibert, R. L., Berkmen, M. B.
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<strong>Clinical report and biochemical analysis of a patient with fumarate hydratase deficiency.</strong>
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Am. J. Med. Genet. 182A: 504-507, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31746132/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31746132</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31746132" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.61415" target="_blank">Full Text</a>]
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Kerrigan, J. F., Aleck, K. A., Tarby, T. J., Bird, C. R., Heidenreich, R. A.
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<strong>Fumaric aciduria: clinical and imaging features.</strong>
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Ann. Neurol. 47: 583-588, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10805328/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10805328</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10805328" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Mroch, A. R., Laudenschlager, M., Flanagan, J. D.
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<strong>Detection of a novel FH whole gene deletion in the propositus leading to subsequent prenatal diagnosis in a sibship with fumarase deficiency.</strong>
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Am. J. Med. Genet. 158A: 155-158, 2012.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22069215/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22069215</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22069215" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.34344" target="_blank">Full Text</a>]
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Petrova-Benedict, R., Robinson, B. H., Stacey, T. E., Mistry, J., Chalmers, R. A.
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<strong>Deficient fumarase activity in an infant with fumaricacidemia and its distribution between the different forms of the enzyme seen on isoelectric focusing.</strong>
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Am. J. Hum. Genet. 40: 257-266, 1987.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3578275/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3578275</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3578275" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Prasad, C., Napier, M. P., Rupar, C. A., Prasad, C.
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<strong>Fumarase deficiency: a rare disorder on the crossroads of clinical and metabolic genetics, neurology and cancer.</strong>
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Clin. Dysmorph. 26: 117-120, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/27541980/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">27541980</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=27541980" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1097/MCD.0000000000000148" target="_blank">Full Text</a>]
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Snodgrass, P. J.
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<strong>Fumarase deficiency. (Letter)</strong>
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New Eng. J. Med. 316: 345 only, 1987.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3807970/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3807970</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3807970" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Whelan, D. T., Hill, R. E., McClorry, S.
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<strong>Fumaric aciduria: a new organic aciduria, associated with mental retardation and speech improvement.</strong>
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Clin. Chim. Acta 132: 301-308, 1983.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6616883/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6616883</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6616883" 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(83)90008-6" target="_blank">Full Text</a>]
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Zinn, A. B., Kerr, D. S., Hoppel, C. L.
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<strong>Fumarase deficiency: a new cause of mitochondrial encephalomyopathy.</strong>
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New Eng. J. Med. 315: 469-475, 1986.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3736629/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3736629</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3736629" 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/10.1056/NEJM198608213150801" target="_blank">Full Text</a>]
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Hilary J. Vernon - updated : 11/18/2022
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Hilary J. Vernon - updated : 08/06/2020<br>Cassandra L. Kniffin - updated : 2/16/2012<br>Cassandra L. Kniffin - updated : 5/20/2008
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Cassandra L. Kniffin : 4/1/2002
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carol : 11/21/2022
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carol : 11/18/2022<br>carol : 10/24/2022<br>carol : 08/06/2020<br>carol : 03/09/2017<br>carol : 10/10/2016<br>carol : 03/12/2015<br>terry : 3/21/2012<br>carol : 2/21/2012<br>ckniffin : 2/16/2012<br>ckniffin : 8/11/2011<br>wwang : 5/23/2008<br>ckniffin : 5/20/2008<br>terry : 4/21/2005<br>carol : 4/4/2002<br>ckniffin : 4/4/2002<br>ckniffin : 4/4/2002
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<strong>#</strong> 606812
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FUMARASE DEFICIENCY; FMRD
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<em>Alternative titles; symbols</em>
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FUMARIC ACIDURIA
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<strong>SNOMEDCT:</strong> 237983002;
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<strong>ORPHA:</strong> 24;
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<strong>DO:</strong> 0111261;
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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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1q43
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Fumarase deficiency
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606812
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Autosomal recessive
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<span class="mim-font">
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3
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FH
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136850
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<p>A number sign (#) is used with this entry because fumarase deficiency (FMRD) is caused by homozygous or compound heterozygous mutation in the fumarate hydratase gene (FH; 136850) on chromosome 1q43.</p><p>Heterozygous mutation in the FH gene can cause hereditary leiomyomatosis and renal cell cancer (HLRCC; 150800).</p>
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<strong>Description</strong>
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<p>Fumarase deficiency (FMRD) is a severe autosomal recessive metabolic disorder characterized by early-onset hypotonia, profound psychomotor retardation, and brain abnormalities, such as agenesis of the corpus callosum, gyral defects, and ventriculomegaly. Many patients show neonatal distress, metabolic acidosis, and/or encephalopathy (summary by Kerrigan et al., 2000 and Mroch et al., 2012). </p>
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<strong>Clinical Features</strong>
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<p>Zinn et al. (1986) reported the case of a male infant with mitochondrial encephalopathy who presented at 1 month of age with failure to thrive, developmental delay, hypotonia, cerebral atrophy, lactic and pyruvic acidemia, and fumaric aciduria. The patient died at 8 months of age. Mitochondria isolated from skeletal muscle showed selective defects in the oxidation of glutamate and succinate, whereas isolated liver mitochondria oxidized these normally. Fumarase activity was virtually absent in mitochondria of both sources. Homogenates of liver and muscle also showed very much reduced fumarase activity, indicating that the cytosolic form of the enzyme was also deficient. Organ differences in intramitochondrial accumulation of fumarase were thought to account for the selective oxidative defects observed in skeletal muscle and not in liver mitochondria. </p><p>Whelan et al. (1983) reported isolated fumaric aciduria in 2 adult sibs with mental retardation and speech impairment. The authors attributed the increased urinary excretion to a defect in renal clearance; fumarase activity was not assessed. Petrova-Benedict et al. (1987) reported a case of fumarase deficiency in a mentally retarded child who presented at 6 months of age with hypotonia, microcephaly, and delayed development. Fumarase was deficient in both the mitochondrial and the cytosolic compartments, but the cytosolic enzyme appeared to be more severely affected. Snodgrass (1987) commented on the occurrence of mild hyperammonemia in fumarase deficiency. Gellera et al. (1990) described the clinical features of fumarase deficiency. A 7-month old boy died in a demented state after a clinical course characterized by generalized seizures, psychomotor deterioration, and fumaric aciduria. Marked deficiency of both mitochondrial and cytosolic fumarases was found in skeletal muscle, brain, cerebellum, heart, kidney, liver, and cultured fibroblasts. Anti-fumarase crossreacting material was present in negligible amounts in these tissues. </p><p>Kerrigan et al. (2000) reported the clinical features of 8 affected members of a large consanguineous family with fumarase deficiency living in an isolated community in the southwestern United States. The ages of the patients ranged from 20 months to 12 years. All patients were profoundly developmentally retarded and had no language development. Only 1 child had achieved independent walking; all the others were unable to sit. All patients had relative macrocephaly and ventricular enlargement. Other common features included hypotonia, seizures, and status epilepticus. Dysmorphic features included frontal bossing, hypertelorism, depressed nasal bridge, anteverted nares, and high-arched palate. Five of 8 had polycythemia at birth. Neuroimaging showed striking abnormalities of the brain, including polymicrogyria, angulation of the frontal horns, decreased periventricular white matter, and small brainstem. Four patients had optic nerve hypoplasia or pallor. </p><p>Mroch et al. (2012) reported 2 brothers, born of unrelated parents, with genetically confirmed FH deficiency resulting in death in infancy. The first boy was born prematurely from a pregnancy complicated by polyhydramnios, and showed hypotonia and respiratory insufficiency after birth. An ultrasound at 20 weeks' gestation had shown agenesis of the corpus callosum, ventriculomegaly, bilateral renal pyelectasis, and a ventriculoseptal defect. Postmortem imaging showed lissencephaly. He developed severe metabolic acidosis, necrotizing enterocolitis, liver failure associated with coagulopathy and hyperbilirubinemia, and encephalopathy, resulting in death at age 22 days. Biochemical studies showed increased urinary tyrosine metabolites, citric cycle intermediates, citrulline, fumaric, malic, and succinic acids, and skin biopsy showed fumarase deficiency. Postmortem examination showed a distended abdomen, and the liver showed intrahepatic bile stasis. Electron microscopy of the liver revealed multiple swollen mitochondria with flat, plate-like, haphazardly arranged cristae. Genetic analysis identified compound heterozygosity for mutations in the FH gene: a point mutation (P174R; 136850.0010) and a whole gene deletion (136850.0011). Prenatal diagnosis confirming the deficiency was performed on the subsequent pregnancy by genetic testing of amniocytes. Ultrasound at 20 weeks' gestation showed ventriculomegaly, dangling choroid plexus, and possible agenesis of the corpus callosum. The parents elected to continue with the pregnancy, but the infant died on day 26. Postmortem examination again showed hepatic involvement, with fibrosis, iron deposition, and bile stasis. Electron microscopy showed abnormal mitochondria similar to that observed in his affected brother. Each unaffected parent was heterozygous for one of the mutations, and neither showed cancer or abnormal cutaneous findings suggesting HLRCC. </p><p>Prasad et al. (2017) reported 2 sisters with an attenuated form of FMRD, including absence of encephalopathy and near-normal urine fumaric acid levels. At age 2.5 years, the older sib was evaluated for failure to thrive and developmental delays. She had a history of constipation and required a gastrostomy tube for feeding issues. She had facial dysmorphisms, including microcephaly, epicanthal folds, bilateral strabismus, low-set ears, a broad nasal bridge, and a tented upper lip. Neurologic examination showed mild ataxia and hypotonia. Before the age of 10 years, she developed focal seizures with secondary generalization. At age 10, she was reported to have appropriate development but unusual behaviors including putting objects in her mouth and causing self-injury. The younger sib was reported to have developmental delay, feeding issues, and dysmorphisms similar to her sister. </p><p>Grocott et al. (2020) reported a patient who was diagnosed with dysphagia, gastrointestinal reflux, and poor weight gain at 18 months of age. At 21 months of age she was nonverbal and could not sit or crawl. Urine organic acid analysis demonstrated increased fumaric acid. She developed myoclonic jerks at 3 years of age, and tonic-clonic seizures at 5 years of age. Seizures persisted despite treatment with multiple antiepileptics. At 12 years of age she had seizures, constipation, developmental delay, truncal hypotonia, joint pain, muscle contractures, and scoliosis. She was nonverbal and nonambulatory. Seizure frequency was decreased after lacosamide was added to her therapeutic regimen. </p>
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<span class="mim-font">
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<strong>Inheritance</strong>
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<p>In the case reported by Petrova-Benedict et al. (1987), the parents of the affected child were first cousins, supporting autosomal recessive inheritance. In the case reported by Gellera et al. (1990), autosomal recessive inheritance was supported by the finding of fumarase activities 30 to 50% of normal in both mitochondria and cytosol from cultured fibroblasts of the parents. </p>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<p>Coughlin et al. (1993) identified a homozygous mutation in the FH gene (136850.0001) in a patient with fumarase deficiency. Bourgeron et al. (1993, 1994) identified a homozygous mutation in the FH gene (136850.0002) in 2 patients with progressive encephalopathy associated with fumarase deficiency. </p><p>In 2 brothers with infantile-lethal fumarase deficiency, Mroch et al. (2012) identified compound heterozygous mutations in the FH gene (136850.0010-136850.0011). </p><p>In 2 sisters with an attenuated form of FMRD, Prasad et al. (2017) identified compound heterozygous mutations in the FH gene: a duplication (K477dup; 136850.0012) and a splice site mutation (136850.0013). The sibs had no encephalopathy and near-normal urine fumaric acid levels. The mutations segregated with the disorder in the family. </p><p>In a patient with FMRD, Grocott et al. (2020) identified compound heterozygous mutations in the FH gene (D65G, 136850.0014; c.1293delA, 136850.0015). Fumarase enzyme was purified from plasmids containing FH with each of the patient's mutations. Fumarase with the c.1293delA mutation had defective enzyme activity and oligomerization. Fumarase with the D65G mutation had a lower catalytic activity compared to wildtype. Urine organic acids in the patient demonstrated elevated fumaric acid, and cytosolic and mitochondrial fumarase enzyme activity were decreased in patient fibroblasts. </p>
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<strong>Population Genetics</strong>
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<p>There is an unusually high incidence of fumarase deficiency in the southwestern United States among members of the Fundamentalist Church of Jesus Christ of Latter Day Saints, a religious community that practices inbreeding and polygamy. The genetic defect was traced to one of the community's founding patriarchs, the late Joseph Smith Jessop, and the first of his plural wives, who had 14 children together (Dougherty, 2005).</p>
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<strong>REFERENCES</strong>
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<p />
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Bourgeron, T., Chretien, D., Poggi-Bach, J., Doonan, S., Rabier, D., Letouze, P., Munnich, A., Rotig, A., Landrieu, P., Rustin, P.
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<strong>Mutation of the fumarase gene in two siblings with progressive encephalopathy and fumarase deficiency.</strong>
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J. Clin. Invest. 93: 2514-2518, 1994.
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[PubMed: 8200987]
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[Full Text: https://doi.org/10.1172/JCI117261]
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Bourgeron, T., Chretien, D., Rotig, A., Munnich, A., Landrieu, P., Rustin, P.
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<strong>Molecular characterization of fumarase deficiency in two children with progressive encephalopathy. (Abstract)</strong>
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Am. J. Hum. Genet. 53 (suppl.): A891 only, 1993.
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<p class="mim-text-font">
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Coughlin, E. M., Chalmers, R. A., Slaugenhaupt, S. A., Gusella, J. F., Shih, V. E., Ramesh, V.
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<strong>Identification of a molecular defect in a fumarase deficient patient and mapping of the fumarase gene. (Abstract)</strong>
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Am. J. Hum. Genet. 53 (suppl.): A896 only, 1993.
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<p class="mim-text-font">
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Dougherty, J.
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<strong>Forbidden fruit: inbreeding among polygamists along the Arizona-Utah border is producing a caste of severely retarded and deformed children.</strong>
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Phoenix New Times, December 29, 2005.
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<p class="mim-text-font">
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Gellera, C., Uziel, G., Rimoldi, M., Zeviani, M., Laverda, A., Carrara, F., DiDonato, S.
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<strong>Fumarase deficiency is an autosomal recessive encephalopathy affecting both the mitochondrial and the cytosolic enzymes.</strong>
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Neurology 40: 495-499, 1990.
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[PubMed: 2314594]
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[Full Text: https://doi.org/10.1212/wnl.40.3_part_1.495]
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<li>
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<p class="mim-text-font">
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Grocott, O., Phanor, S. K., Fung, F., Thibert, R. L., Berkmen, M. B.
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<strong>Clinical report and biochemical analysis of a patient with fumarate hydratase deficiency.</strong>
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Am. J. Med. Genet. 182A: 504-507, 2020.
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[PubMed: 31746132]
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[Full Text: https://doi.org/10.1002/ajmg.a.61415]
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</li>
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<li>
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<p class="mim-text-font">
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Kerrigan, J. F., Aleck, K. A., Tarby, T. J., Bird, C. R., Heidenreich, R. A.
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<strong>Fumaric aciduria: clinical and imaging features.</strong>
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Ann. Neurol. 47: 583-588, 2000.
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[PubMed: 10805328]
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<li>
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<p class="mim-text-font">
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Mroch, A. R., Laudenschlager, M., Flanagan, J. D.
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<strong>Detection of a novel FH whole gene deletion in the propositus leading to subsequent prenatal diagnosis in a sibship with fumarase deficiency.</strong>
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Am. J. Med. Genet. 158A: 155-158, 2012.
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[PubMed: 22069215]
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[Full Text: https://doi.org/10.1002/ajmg.a.34344]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Petrova-Benedict, R., Robinson, B. H., Stacey, T. E., Mistry, J., Chalmers, R. A.
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<strong>Deficient fumarase activity in an infant with fumaricacidemia and its distribution between the different forms of the enzyme seen on isoelectric focusing.</strong>
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Am. J. Hum. Genet. 40: 257-266, 1987.
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[PubMed: 3578275]
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<li>
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<p class="mim-text-font">
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Prasad, C., Napier, M. P., Rupar, C. A., Prasad, C.
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<strong>Fumarase deficiency: a rare disorder on the crossroads of clinical and metabolic genetics, neurology and cancer.</strong>
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Clin. Dysmorph. 26: 117-120, 2017.
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[PubMed: 27541980]
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[Full Text: https://doi.org/10.1097/MCD.0000000000000148]
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<li>
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<p class="mim-text-font">
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Snodgrass, P. J.
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<strong>Fumarase deficiency. (Letter)</strong>
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New Eng. J. Med. 316: 345 only, 1987.
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[PubMed: 3807970]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Whelan, D. T., Hill, R. E., McClorry, S.
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<strong>Fumaric aciduria: a new organic aciduria, associated with mental retardation and speech improvement.</strong>
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Clin. Chim. Acta 132: 301-308, 1983.
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[PubMed: 6616883]
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[Full Text: https://doi.org/10.1016/0009-8981(83)90008-6]
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Zinn, A. B., Kerr, D. S., Hoppel, C. L.
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<strong>Fumarase deficiency: a new cause of mitochondrial encephalomyopathy.</strong>
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New Eng. J. Med. 315: 469-475, 1986.
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[PubMed: 3736629]
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[Full Text: https://doi.org/10.1056/NEJM198608213150801]
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Hilary J. Vernon - updated : 11/18/2022<br>Hilary J. Vernon - updated : 08/06/2020<br>Cassandra L. Kniffin - updated : 2/16/2012<br>Cassandra L. Kniffin - updated : 5/20/2008
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