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Entry
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- #616277 - MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 DEFICIENCY; ECHS1D
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- OMIM
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<p>
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<span class="h4">#616277</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<a href="#title"><strong>Title</strong></a>
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<li role="presentation">
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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</li>
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<li role="presentation">
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<a href="/clinicalSynopsis/616277"><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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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div style="display: table-cell;">External Links</div>
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</a>
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</h4>
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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<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=MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 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=31914&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/NBK542806/" 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.ncbi.nlm.nih.gov/gtr/all/tests/?term=616277[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=653880" 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 style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/disease/DOID:0070540" 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/616277" 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:0070540" 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>
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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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</span>
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</div>
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<div>
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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>ORPHA:</strong> 653880<br />
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<strong>DO:</strong> 0070540<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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616277
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</span>
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</span>
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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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MITOCHONDRIAL SHORT-CHAIN ENOYL-CoA HYDRATASE 1 DEFICIENCY; ECHS1D
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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="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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</tr>
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</thead>
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
|
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<a href="/geneMap/10/680?start=-3&limit=10&highlight=680">
|
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10q26.3
|
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</a>
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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Mitochondrial short-chain enoyl-CoA hydratase 1 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/616277"> 616277 </a>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</td>
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<td>
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<span class="mim-font">
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ECHS1
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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/602292"> 602292 </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 class="btn-group ">
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<a href="/clinicalSynopsis/616277" class="btn btn-warning" role="button"> Clinical Synopsis </a>
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<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="sr-only">Toggle Dropdown</span>
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
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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/616277" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/616277" 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">
|
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<strong> HEAD & NECK </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
|
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<em> Ears </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
|
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|
|
- Hearing impairment (1 patient) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/103276001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">103276001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/15188001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">15188001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H91.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H91.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/389.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.9</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/389" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1384666&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1384666</a>, <a href="https://bioportal.bioontology.org/search?q=C1550444&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1550444</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000365" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000365</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000365" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000365</a>]</span><br />
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</span>
|
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</div>
|
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</div>
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<div>
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<div>
|
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<span class="h5 mim-font">
|
|
<em> Eyes </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Nystagmus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/563001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">563001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/379.50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">379.50</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0028738&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0028738</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span><br />
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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>
|
|
<span class="h5 mim-font">
|
|
<strong> CARDIOVASCULAR </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> Heart </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Ventricular septal defect (in some patient) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/30288003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">30288003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253549006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253549006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/768552007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">768552007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/745.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">745.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018818&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018818</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001629" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001629</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001629" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001629</a>]</span><br /> -
|
|
Obstructive hypertrophic cardiomyopathy (1 patient) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/45227007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">45227007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I42.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/425.11" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">425.11</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551472&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551472</a>]</span><br />
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|
|
|
</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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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> RESPIRATORY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Apnea, episodic <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3806500&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3806500</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248583008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248583008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1023001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1023001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R06.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R06.81</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/786.03" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">786.03</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002104" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002104</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
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|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
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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 /> -
|
|
Secondarily decreased activities of mitochondrial respiratory enzymes (1 patient) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4229209&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4229209</a>]</span><br />
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|
|
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</span>
|
|
</div>
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</div>
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</div>
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEUROLOGIC </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
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|
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|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Central Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Delayed psychomotor development, severe <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1847696&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1847696</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/224958001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">224958001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F88</a>]</span> <span class="mim-feature-ids hidden">[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 /> -
|
|
Spasticity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/221360009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">221360009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/397790002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">397790002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026838&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026838</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001257" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001257</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001257" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001257</a>]</span><br /> -
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Dystonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/15802004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">15802004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G24.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G24.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/G24" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G24</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013421</a>, <a href="https://bioportal.bioontology.org/search?q=C0393593&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0393593</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001332" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001332</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001332" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001332</a>]</span><br /> -
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Abnormal T2-weighted hyperintensities in the basal ganglia consistent with Leigh syndrome <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4229210&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4229210</a>]</span><br />
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- Increased serum lactate <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5888306&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5888306</a>, <a href="https://bioportal.bioontology.org/search?q=C1836440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002151" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002151</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002151" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002151</a>]</span><br /> -
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Increased 3-methylglutaconic acid <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5436355&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5436355</a>]</span><br /> -
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Increased CSF lactate <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1167918&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1167918</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002490" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002490</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002490" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002490</a>]</span><br /> -
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Increased urinary glyoxylate (1 patient) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4229207&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4229207</a>]</span><br /> -
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Secondarily decreased activity of the pyruvate dehydrogenase complex (PDC) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4229206&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4229206</a>]</span><br /> -
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Increased urinary S-(2-carboxypropyl)cysteine <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4229205&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4229205</a>]</span><br /> -
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Increased 2-methyl-2,3-dihydroxybutyrate <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4229204&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4229204</a>]</span><br />
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<strong> MISCELLANEOUS </strong>
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- Onset at birth or infancy<br /> -
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Severe disorder <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/64572001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">64572001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0012634&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0012634</a>]</span><br /> -
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Exacerbation or regression during viral infection<br />
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<strong> MOLECULAR BASIS </strong>
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- Caused by mutation in the mitochondrial enoyl-CoA hydratase, short-chain, 1 gene (ECHS1, <a href="/entry/602292#0001">602292.0001</a>)<br />
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</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-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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<p>A number sign (#) is used with this entry because of evidence that mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D) is caused by homozygous or compound heterozygous mutation in the ECHS1 gene (<a href="/entry/602292">602292</a>) on chromosome 10q26.</p>
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<strong>Description</strong>
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<p>Mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D) is an autosomal recessive inborn error of metabolism characterized by severely delayed psychomotor development, neurodegeneration, increased lactic acid, and brain lesions in the basal ganglia (summary by <a href="#4" class="mim-tip-reference" title="Peters, H., Buck, N., Wanders, R., Ruiter, J., Waterham, H., Koster, J., Yaplito-Lee, J., Ferdinandusse, S., Pitt, J. <strong>ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism.</strong> Brain 137: 2903-2908, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25125611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25125611</a>] [<a href="https://doi.org/10.1093/brain/awu216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25125611">Peters et al., 2014</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25125611" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>Clinical Features</strong>
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<p><a href="#4" class="mim-tip-reference" title="Peters, H., Buck, N., Wanders, R., Ruiter, J., Waterham, H., Koster, J., Yaplito-Lee, J., Ferdinandusse, S., Pitt, J. <strong>ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism.</strong> Brain 137: 2903-2908, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25125611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25125611</a>] [<a href="https://doi.org/10.1093/brain/awu216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25125611">Peters et al. (2014)</a> reported 2 sibs, born of unrelated parents of Greek ancestry, with a severe neurologic disorder resulting in death from cardiorespiratory failure at ages 4 and 8 months. Both patients presented at birth with hypotonia, poor suck, and episodic apnea. One of the patients also had vertical nystagmus as well as cardiac abnormalities, including ventricular septal defect and severe progressive hypertrophic obstructive cardiomyopathy. The patients showed little developmental progress. Brain imaging showed progressive generalized atrophy of the cerebrum, brainstem, and cerebellum, thinning of the corpus callosum, and T2-weighted hyperintensities in the basal ganglia, consistent with a clinical diagnosis of Leigh syndrome. Laboratory studies revealed increased serum and cerebrospinal fluid lactate, and both patients had decreased activities of the pyruvate dehydrogenase complex (PDC). Skeletal muscle biopsy of 1 of the patients showed normal activities of mitochondrial respiratory chain enzymes. Urinary analysis showed increased levels of S-(2-carboxypropyl)cysteine, suggesting a defect in the valine catabolic pathway. The patients also had increased levels of 2-methyl-2,3-dihydroxybutyrate. Additional studies showed normal levels of 3-hydroxyisobutyryl-carnitine, suggesting a defect in ECHS1 rather than HIBCH (<a href="/entry/610690">610690</a>); sequencing of the HIBCH gene did not reveal any pathogenic mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25125611" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Sakai, C., Yamaguchi, S., Sasaki, M., Miyamoto, Y., Matsushima, Y., Goto, Y. <strong>ECHS1 mutations cause combined respiratory chain deficiency resulting in Leigh syndrome.</strong> Hum. Mutat. 36: 232-239, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25393721/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25393721</a>] [<a href="https://doi.org/10.1002/humu.22730" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25393721">Sakai et al. (2015)</a> reported a 4-year-old boy, born of unrelated parents, with a severe neurologic disorder apparent since early infancy. He had delayed psychomotor development with inability to sit unsupported as well as absence of speech, hearing impairment, nystagmus, hypotonia, spasticity, and athetotic movements. Brain imaging showed T2-weighted hyperintensities consistent with Leigh syndrome. Laboratory studies showed increased lactate and increased urinary glyoxylate. Skeletal muscle samples showed a combined deficiency of the activities of mitochondrial respiratory enzymes, including complex I (39% of controls), complex III (34% of controls), and complex IV (64% of controls), although electrophoresis studies showed that assembly of these complexes was normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25393721" 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="Yamada, K., Aiba, K., Kitaura, Y., Kondo, Y., Nomura, N., Nakamura, Y., Fukushi, D., Murayama, K., Shimomura, Y., Pitt, J., Yamaguchi, S., Yokochi, K., Wakamatsu, N. <strong>Clinical, biochemical and metabolic characterisation of a mild form of human short-chain enoyl-CoA hydratase deficiency: significance of increased N-acetyl-S-(2-carboxypropyl)cysteine excretion.</strong> J. Med. Genet. 52: 691-698, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26251176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26251176</a>] [<a href="https://doi.org/10.1136/jmedgenet-2015-103231" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26251176">Yamada et al. (2015)</a> reported a 7-year-old girl and her 5-year-old brother with ECHS1D, who were born of unrelated Japanese parents. Both sibs presented with dystonia between 7 and 10 months of age, after which regression of psychomotor development became apparent. Brain imaging showed T2-weighted hyperintensities in the putamen, globus pallidus, caudate nucleus, and substantia nigra. At examination, both patients bent backward forcefully and had no language. Neither patient had seizures. The condition worsened with viral infection, resulting in death in the 5-year-old boy. Analysis of mitochondrial respiratory chain activities was normal in the fibroblasts of the older sister, and blood and cerebrospinal fluid lactate were not increased, but urinary lactate was increased. There was also increased urinary N-acetyl-S-cysteine, a metabolite of methacrylyl-CoA, and mildly increased 2,3-dihydroxy-2-methylbutyrate. <a href="#8" class="mim-tip-reference" title="Yamada, K., Aiba, K., Kitaura, Y., Kondo, Y., Nomura, N., Nakamura, Y., Fukushi, D., Murayama, K., Shimomura, Y., Pitt, J., Yamaguchi, S., Yokochi, K., Wakamatsu, N. <strong>Clinical, biochemical and metabolic characterisation of a mild form of human short-chain enoyl-CoA hydratase deficiency: significance of increased N-acetyl-S-(2-carboxypropyl)cysteine excretion.</strong> J. Med. Genet. 52: 691-698, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26251176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26251176</a>] [<a href="https://doi.org/10.1136/jmedgenet-2015-103231" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26251176">Yamada et al. (2015)</a> concluded that the patients had a relatively milder form of ECHS1D with defective valine catabolic and beta-oxidation pathways, and suggested that N-acetyl-S-cysteine would be a good candidate metabolic marker for the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26251176" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Haack, T. B., Jackson, C. B., Murayama, K., Kremer, L. S., Schaller, A., Kotzaeridou, U., de Vries, M. C., Schottmann, G., Santra, S., Buchner, B., Wieland, T., Graf, E., and 28 others. <strong>Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac involvement.</strong> Ann. Clin. Transl. Neurol. 2: 492-509, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26000322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26000322</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26000322[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/acn3.189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26000322">Haack et al. (2015)</a> reported 10 unrelated individuals who presented with a combination of mitochondrial encephalopathy, deafness, epilepsy, optic nerve atrophy, and cardiomyopathy. Brain MRIs were performed in 9 patients and showed white matter changes in 5 early-onset, severely affected patients, and bilateral T2 hyperintensities in the basal ganglia in 4 less severely affected patients. MR spectroscopy of the basal ganglia showed elevated lactate in 3 of 7 individuals. 2-Methyl-2,3,-dihydroxybutyrate was elevated in the urine of 3 of 4 patients tested, and higher levels appeared to correlate with severe disease expression. Four patients died before the age of 7.5 (range, 4 months to 7.5 years) and 6 patients were alive at the time of reporting (range, 2-31 years). Analysis of enzymes involved in oxidative phosphorylation in muscle tissue and/or fibroblasts showed mild and inconsistent changes in 4 of 8 patients tested, including abnormalities in pyruvate oxidation or ATP production and decreased activity of complex I or complex IV, in 1 patient each. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26000322" 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="Tetreault, M., Fahiminiya, S., Antonicka, H., Mitchell, G. A., Geraghty, M. T., Lines, M., Boycott, K. M., Shoubridge, E. A., Mitchell, J. J., Care4Rare Canada Consortium, Michaud, J. L., Majewski, J. <strong>Whole-exome sequencing identifies novel ECHS1 mutations in Leigh syndrome.</strong> Hum. Genet. 134: 981-991, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26099313/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26099313</a>] [<a href="https://doi.org/10.1007/s00439-015-1577-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26099313">Tetreault et al. (2015)</a> reported 4 patients from 3 apparently unrelated French Canadian families who had developmental regression in early infancy, failure to thrive, and nystagmus. Three patients had optic atrophy and sensorineural hearing loss. Three patients had episodic neurologic changes, and in 2 the changes were in the context of viral infections. All 4 patients had brain MRI abnormalities including T2 weighted hyperintensities of the basal ganglia. MRS showed a lactate peak in 1 patient. Studies in patient fibroblasts showed normal pyruvate dehydrogenase activity in 2 patients and slightly decreased pyruvate dehydrogenase activity in 1 patient. Cytochrome c oxidase and succinate cytochrome c reductase activity was normal in fibroblasts from all patients. Respiratory chain studies in muscle showed a slight reduction in complex I and complex III activity in 1 patient, and normal activity in the other 3 patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26099313" 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="#2" class="mim-tip-reference" title="Fitzsimons, P. E., Alston, C. L., Bonnen, P. E., Hughes, J., Crushell, E., Geraghty, M. T., Tetreault, M., O'Reilly, P., Twomey, E., Sheikh, Y., Walsh, R., Waterham, H. R., Ferdinandusse, S., Wanders, R. J. A., Taylor, R. W., Pitt, J. J., Mayne, P. D. <strong>Clinical, biochemical, and genetic features of four patients with short-chain enoyl-CoA hydratase (ECHS1) deficiency.</strong> Am. J. Med. Genet. 176A: 1115-1127, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29575569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29575569</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29575569[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.38658" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29575569">Fitzsimons et al. (2018)</a> reported 4 patients with ECHS1D, 3 of whom were sibs. Age range of clinical presentation was 2 weeks to 5 months. All 4 patients had elevated erythro-2,3-dihydroxy-2-methylbutyrate and 3-methylglutaconic acid on urine organic acids. In 2 patients, analysis of urine metabolites showed elevated acryloyl cysteamine, N-acetyl-acryloyl-cysteine, methacryl-L-cysteine, and N-acetyl-methacryl-cysteine. All patients also had at least one elevated plasma lactate measurement. MRIs in all patients showed abnormal signal in the bilateral basal ganglia. In 2 patients, prominent sulci and volume loss were noted. In 1 patient there was thinning of the corpus callosum and cerebral and cerebellar atrophy. Three patients had a lactate peak on MRS, and 3 patients had seizures. All patients had developmental delay with regression, and all required feeding support for poor weight gain, 1 via nasogastric tube and 3 via PEG tube. All patients were deceased, with age of death ranging from 13 months to 4 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29575569" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The transmission pattern of ECHS1D in the family reported by <a href="#4" class="mim-tip-reference" title="Peters, H., Buck, N., Wanders, R., Ruiter, J., Waterham, H., Koster, J., Yaplito-Lee, J., Ferdinandusse, S., Pitt, J. <strong>ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism.</strong> Brain 137: 2903-2908, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25125611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25125611</a>] [<a href="https://doi.org/10.1093/brain/awu216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25125611">Peters et al. (2014)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25125611" 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 2 sibs with ECHS1D, <a href="#4" class="mim-tip-reference" title="Peters, H., Buck, N., Wanders, R., Ruiter, J., Waterham, H., Koster, J., Yaplito-Lee, J., Ferdinandusse, S., Pitt, J. <strong>ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism.</strong> Brain 137: 2903-2908, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25125611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25125611</a>] [<a href="https://doi.org/10.1093/brain/awu216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25125611">Peters et al. (2014)</a> identified compound heterozygous mutations in the ECHS1 gene (A158D, <a href="/entry/602292#0001">602292.0001</a> and c.414+3G-C, <a href="/entry/602292#0002">602292.0002</a>). Patient fibroblasts showed significantly decreased ECHS1 activity and absence of the normal protein by immunoblot analysis. <a href="#4" class="mim-tip-reference" title="Peters, H., Buck, N., Wanders, R., Ruiter, J., Waterham, H., Koster, J., Yaplito-Lee, J., Ferdinandusse, S., Pitt, J. <strong>ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism.</strong> Brain 137: 2903-2908, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25125611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25125611</a>] [<a href="https://doi.org/10.1093/brain/awu216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25125611">Peters et al. (2014)</a> postulated that the enzymatic defect caused accumulation of the metabolites methacrylyl-CoA and acryloyl-CoA, which are toxic reactive intermediates that may have caused the brain pathology. Decreased activity of the PDC may also have been a secondary effect. The metabolic abnormalities in these patients appeared to be confined to the valine pathway, since fatty acid and isoleucine metabolites were normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25125611" 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 boy with ECHS1D, <a href="#5" class="mim-tip-reference" title="Sakai, C., Yamaguchi, S., Sasaki, M., Miyamoto, Y., Matsushima, Y., Goto, Y. <strong>ECHS1 mutations cause combined respiratory chain deficiency resulting in Leigh syndrome.</strong> Hum. Mutat. 36: 232-239, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25393721/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25393721</a>] [<a href="https://doi.org/10.1002/humu.22730" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25393721">Sakai et al. (2015)</a> identified compound heterozygous mutations in the ECHS1 gene (M1R, <a href="/entry/602292#0003">602292.0003</a> and A2V, <a href="/entry/602292#0004">602292.0004</a>). The mutations, which were found by targeted exome sequencing, segregated with the disorder in the family. Patient cells also showed a combined mitochondrial respiratory chain deficiency, which was rescued by expression of wildtype ECHS1. These findings suggested a link between ECHS1 and the mitochondrial respiratory chain. <a href="#5" class="mim-tip-reference" title="Sakai, C., Yamaguchi, S., Sasaki, M., Miyamoto, Y., Matsushima, Y., Goto, Y. <strong>ECHS1 mutations cause combined respiratory chain deficiency resulting in Leigh syndrome.</strong> Hum. Mutat. 36: 232-239, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25393721/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25393721</a>] [<a href="https://doi.org/10.1002/humu.22730" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25393721">Sakai et al. (2015)</a> speculated that ECHS1 deficiency induced metabolic abnormalities resulting in the accumulation of toxic metabolites, such as glyoxylate, that secondarily inhibited normal mitochondrial respiratory function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25393721" 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 sibs, born of unrelated Japanese parents, with ECHS1D, <a href="#8" class="mim-tip-reference" title="Yamada, K., Aiba, K., Kitaura, Y., Kondo, Y., Nomura, N., Nakamura, Y., Fukushi, D., Murayama, K., Shimomura, Y., Pitt, J., Yamaguchi, S., Yokochi, K., Wakamatsu, N. <strong>Clinical, biochemical and metabolic characterisation of a mild form of human short-chain enoyl-CoA hydratase deficiency: significance of increased N-acetyl-S-(2-carboxypropyl)cysteine excretion.</strong> J. Med. Genet. 52: 691-698, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26251176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26251176</a>] [<a href="https://doi.org/10.1136/jmedgenet-2015-103231" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26251176">Yamada et al. (2015)</a> identified compound heterozygous missense mutations in the ECHS1 gene (N59S, <a href="/entry/602292#0005">602292.0005</a> and A138V, <a href="/entry/602292#0006">602292.0006</a>). The mutations, which were found by a combination of linkage analysis and whole-exome sequencing, segregated with the disorder in the family. ECHS1 activity towards different substrates was decreased to between 2.6% and 6.2% of normal controls. In vitro functional expression studies showed that the D59S mutant was nonfunctional, whereas the A138V mutant had about 30% residual activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26251176" 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 10 unrelated families segregating ECHS1D, <a href="#3" class="mim-tip-reference" title="Haack, T. B., Jackson, C. B., Murayama, K., Kremer, L. S., Schaller, A., Kotzaeridou, U., de Vries, M. C., Schottmann, G., Santra, S., Buchner, B., Wieland, T., Graf, E., and 28 others. <strong>Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac involvement.</strong> Ann. Clin. Transl. Neurol. 2: 492-509, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26000322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26000322</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26000322[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/acn3.189" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26000322">Haack et al. (2015)</a> identified homozygous or compound heterozygous mutations in the ECHS1 gene. In 1 family (F3), 3 affected sibs (proband 68552), born to consanguineous Pakistani parents, were homozygous for a missense mutation (Q159R; <a href="/entry/602292#0007">602292.0007</a>). In 2 unrelated families (F1 and F10), patient 346 and patient 52236 were compound heterozygous for the Q159R mutation and different second mutations (N59S, <a href="/entry/602292#0008">602292.0008</a> and E77Q, <a href="/entry/602292#0009">602292.0009</a>), respectively. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Immunoblotting on fibroblasts from the 2 compound heterozygous patients showed reduced expression of the ECHS1 protein and reduced palmitate-dependent respiration; fibroblasts from 1 of these patients showed reduced 2-enoyl-CoA hydratase activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26000322" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 4 patients with ECHS1D from 3 unrelated French Canadian families, <a href="#7" class="mim-tip-reference" title="Tetreault, M., Fahiminiya, S., Antonicka, H., Mitchell, G. A., Geraghty, M. T., Lines, M., Boycott, K. M., Shoubridge, E. A., Mitchell, J. J., Care4Rare Canada Consortium, Michaud, J. L., Majewski, J. <strong>Whole-exome sequencing identifies novel ECHS1 mutations in Leigh syndrome.</strong> Hum. Genet. 134: 981-991, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26099313/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26099313</a>] [<a href="https://doi.org/10.1007/s00439-015-1577-y" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26099313">Tetreault et al. (2015)</a> identified compound heterozygous mutations in the ECHS1 gene. All 3 had a T180A missense mutation (<a href="/entry/602292#0010">602292.0010</a>) with a different second mutation (see, e.g., <a href="/entry/602292#0011">602292.0011</a> and <a href="/entry/602292#0012">602292.0012</a>). All of the mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing. All 4 mutations occurred in the ECHS1 enoyl-CoA hydratase/isomerase domain and were predicted to decrease protein stability. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26099313" 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 3 Irish Traveler sibs and a Pakistani patient with ECHS1D, <a href="#2" class="mim-tip-reference" title="Fitzsimons, P. E., Alston, C. L., Bonnen, P. E., Hughes, J., Crushell, E., Geraghty, M. T., Tetreault, M., O'Reilly, P., Twomey, E., Sheikh, Y., Walsh, R., Waterham, H. R., Ferdinandusse, S., Wanders, R. J. A., Taylor, R. W., Pitt, J. J., Mayne, P. D. <strong>Clinical, biochemical, and genetic features of four patients with short-chain enoyl-CoA hydratase (ECHS1) deficiency.</strong> Am. J. Med. Genet. 176A: 1115-1127, 2018.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29575569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29575569</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29575569[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.38658" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29575569">Fitzsimons et al. (2018)</a> identified homozygosity for the previously identified T180A and Q159R mutations in the ECHS1 gene, respectively. Erythro-2,3-dihydroxy-2-methylbutyrate and 3-methylglutaconic acid were elevated on urine organic acids of all patients. Muscle and fibroblast testing was carried out in 1 sib and the Pakistani patient. Fibroblasts showed markedly decreased ECHS1 enzyme activity and absence of ECHS1 on Western blot analysis. PDH activity and beta oxidation studies were normal. Activities of respiratory chain complexes I, II, and IV were normal, and activity of complexes II+III was decreased in muscle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29575569" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 4 patients, including 3 sibs, from 2 families with Samoan heritage with ECHS1D, <a href="#6" class="mim-tip-reference" title="Simon, M. T., Eftekharian, S. S., Ferdinandusse, S., Tang, S., Naseri, T., Reupena, M. S., McGarvey, S. T., Minster, R. L., Weeks, D. E., Samoan Obesity, Lifestyle, and Genetic Adaptations (OLaGA) Study Group, Nguyen, D. D., Lee, S., Ellsworth, K. A., Vaz, F. M., Dimmock, D., Pitt, J., Abdenur, J. E. <strong>ECHS1 disease in two unrelated families of Samoan descent: common variant--rare disorder.</strong> Am. J. Med. Genet. 185A: 157-167, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33112498/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33112498</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33112498[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.61936" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33112498">Simon et al. (2021)</a> identified compound heterozygous mutations in the ECHS1 gene (A278T, <a href="/entry/602292#0012">602292.0012</a> and P163P, <a href="/entry/602292#0013">602292.0013</a>). ECHS1 protein expression and activity were reduced in fibroblasts from the carrier parents from family 1 and reduced to a greater degree in their affected offspring. ECHS1 protein expression and activity were also reduced in fibroblasts from the patient in family 2. Analysis of mRNA in fibroblasts from the unaffected Samoan mother from family 1, who was homozygous for the P163P variant, and from one of her affected children demonstrated that the P163P variant resulted in abnormal splicing with skipping of exon 4. Family 1 was previously reported by <a href="#1" class="mim-tip-reference" title="Abdenur, J. E., Sowa, M., Simon, M., Steenari, M., Skaar, J., Eftekharian, S., Chang, R., Ferdinandusse, S., Pitt, J. <strong>Medical nutrition therapy in patients with HIBCH and ECHS1 defects: clinical and biochemical response to low valine diet.</strong> Molec. Genet. Metab. Rep. 24: 100617, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32642440/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32642440</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32642440[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/j.ymgmr.2020.100617" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32642440">Abdenur et al. (2020)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=33112498+32642440" 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="#6" class="mim-tip-reference" title="Simon, M. T., Eftekharian, S. S., Ferdinandusse, S., Tang, S., Naseri, T., Reupena, M. S., McGarvey, S. T., Minster, R. L., Weeks, D. E., Samoan Obesity, Lifestyle, and Genetic Adaptations (OLaGA) Study Group, Nguyen, D. D., Lee, S., Ellsworth, K. A., Vaz, F. M., Dimmock, D., Pitt, J., Abdenur, J. E. <strong>ECHS1 disease in two unrelated families of Samoan descent: common variant--rare disorder.</strong> Am. J. Med. Genet. 185A: 157-167, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33112498/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33112498</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33112498[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.61936" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33112498">Simon et al. (2021)</a> identified a synonymous P163P variant in the ECHS1 gene (<a href="/entry/602292#0013">602292.0013</a>) at an allele frequency of 0.17 in the Samoan population, with 34 homozygotes detected. This frequency did not suggest decreased fitness in individuals with homozygosity for the variant; however, <a href="#6" class="mim-tip-reference" title="Simon, M. T., Eftekharian, S. S., Ferdinandusse, S., Tang, S., Naseri, T., Reupena, M. S., McGarvey, S. T., Minster, R. L., Weeks, D. E., Samoan Obesity, Lifestyle, and Genetic Adaptations (OLaGA) Study Group, Nguyen, D. D., Lee, S., Ellsworth, K. A., Vaz, F. M., Dimmock, D., Pitt, J., Abdenur, J. E. <strong>ECHS1 disease in two unrelated families of Samoan descent: common variant--rare disorder.</strong> Am. J. Med. Genet. 185A: 157-167, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33112498/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33112498</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33112498[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1002/ajmg.a.61936" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33112498">Simon et al. (2021)</a> found the variant to be disease causing when in trans with a severe mutation on the other ECHS1 allele. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33112498" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="1" class="mim-anchor"></a>
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<a id="Abdenur2020" class="mim-anchor"></a>
|
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|
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Abdenur, J. E., Sowa, M., Simon, M., Steenari, M., Skaar, J., Eftekharian, S., Chang, R., Ferdinandusse, S., Pitt, J.
|
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<strong>Medical nutrition therapy in patients with HIBCH and ECHS1 defects: clinical and biochemical response to low valine diet.</strong>
|
|
Molec. Genet. Metab. Rep. 24: 100617, 2020.
|
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|
|
|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32642440/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32642440</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=32642440[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32642440" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ymgmr.2020.100617" target="_blank">Full Text</a>]
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|
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<a id="2" class="mim-anchor"></a>
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|
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Fitzsimons, P. E., Alston, C. L., Bonnen, P. E., Hughes, J., Crushell, E., Geraghty, M. T., Tetreault, M., O'Reilly, P., Twomey, E., Sheikh, Y., Walsh, R., Waterham, H. R., Ferdinandusse, S., Wanders, R. J. A., Taylor, R. W., Pitt, J. J., Mayne, P. D.
|
|
<strong>Clinical, biochemical, and genetic features of four patients with short-chain enoyl-CoA hydratase (ECHS1) deficiency.</strong>
|
|
Am. J. Med. Genet. 176A: 1115-1127, 2018.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29575569/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29575569</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29575569[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29575569" 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.38658" target="_blank">Full Text</a>]
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|
|
</li>
|
|
|
|
<li>
|
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<a id="3" class="mim-anchor"></a>
|
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<a id="Haack2015" class="mim-anchor"></a>
|
|
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|
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|
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Haack, T. B., Jackson, C. B., Murayama, K., Kremer, L. S., Schaller, A., Kotzaeridou, U., de Vries, M. C., Schottmann, G., Santra, S., Buchner, B., Wieland, T., Graf, E., and 28 others.
|
|
<strong>Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac involvement.</strong>
|
|
Ann. Clin. Transl. Neurol. 2: 492-509, 2015.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26000322/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26000322</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=26000322[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26000322" 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/acn3.189" target="_blank">Full Text</a>]
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Peters, H., Buck, N., Wanders, R., Ruiter, J., Waterham, H., Koster, J., Yaplito-Lee, J., Ferdinandusse, S., Pitt, J.
|
|
<strong>ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism.</strong>
|
|
Brain 137: 2903-2908, 2014.
|
|
|
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25125611/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25125611</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25125611" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/brain/awu216" target="_blank">Full Text</a>]
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Sakai, C., Yamaguchi, S., Sasaki, M., Miyamoto, Y., Matsushima, Y., Goto, Y.
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<strong>ECHS1 mutations cause combined respiratory chain deficiency resulting in Leigh syndrome.</strong>
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Hum. Mutat. 36: 232-239, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25393721/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25393721</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25393721" 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/humu.22730" target="_blank">Full Text</a>]
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Simon, M. T., Eftekharian, S. S., Ferdinandusse, S., Tang, S., Naseri, T., Reupena, M. S., McGarvey, S. T., Minster, R. L., Weeks, D. E., Samoan Obesity, Lifestyle, and Genetic Adaptations (OLaGA) Study Group, Nguyen, D. D., Lee, S., Ellsworth, K. A., Vaz, F. M., Dimmock, D., Pitt, J., Abdenur, J. E.
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<strong>ECHS1 disease in two unrelated families of Samoan descent: common variant--rare disorder.</strong>
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Am. J. Med. Genet. 185A: 157-167, 2021.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33112498/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33112498</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=33112498[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33112498" 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.61936" target="_blank">Full Text</a>]
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Tetreault, M., Fahiminiya, S., Antonicka, H., Mitchell, G. A., Geraghty, M. T., Lines, M., Boycott, K. M., Shoubridge, E. A., Mitchell, J. J., Care4Rare Canada Consortium, Michaud, J. L., Majewski, J.
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<strong>Whole-exome sequencing identifies novel ECHS1 mutations in Leigh syndrome.</strong>
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Hum. Genet. 134: 981-991, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26099313/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26099313</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26099313" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Yamada, K., Aiba, K., Kitaura, Y., Kondo, Y., Nomura, N., Nakamura, Y., Fukushi, D., Murayama, K., Shimomura, Y., Pitt, J., Yamaguchi, S., Yokochi, K., Wakamatsu, N.
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<strong>Clinical, biochemical and metabolic characterisation of a mild form of human short-chain enoyl-CoA hydratase deficiency: significance of increased N-acetyl-S-(2-carboxypropyl)cysteine excretion.</strong>
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J. Med. Genet. 52: 691-698, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26251176/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26251176</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26251176" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Hilary J. Vernon - updated : 08/05/2024
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Hilary J. Vernon - updated : 07/13/2020<br>Cassandra L. Kniffin - updated : 12/21/2015
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Cassandra L. Kniffin : 3/23/2015
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carol : 07/10/2023<br>carol : 07/07/2023<br>carol : 07/13/2020<br>carol : 04/25/2017<br>carol : 12/29/2015<br>ckniffin : 12/21/2015<br>carol : 3/25/2015<br>mcolton : 3/24/2015<br>ckniffin : 3/24/2015
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<strong>Phenotype-Gene Relationships</strong>
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</h4>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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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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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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10q26.3
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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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Mitochondrial short-chain enoyl-CoA hydratase 1 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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616277
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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<td>
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<span class="mim-font">
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3
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<span class="mim-font">
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ECHS1
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</td>
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<td>
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<span class="mim-font">
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602292
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<h4>
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<span class="mim-font">
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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 of evidence that mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D) is caused by homozygous or compound heterozygous mutation in the ECHS1 gene (602292) on chromosome 10q26.</p>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</h4>
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<span class="mim-text-font">
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<p>Mitochondrial short-chain enoyl-CoA hydratase-1 deficiency (ECHS1D) is an autosomal recessive inborn error of metabolism characterized by severely delayed psychomotor development, neurodegeneration, increased lactic acid, and brain lesions in the basal ganglia (summary by Peters et al., 2014). </p>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Clinical Features</strong>
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</span>
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</h4>
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<p>Peters et al. (2014) reported 2 sibs, born of unrelated parents of Greek ancestry, with a severe neurologic disorder resulting in death from cardiorespiratory failure at ages 4 and 8 months. Both patients presented at birth with hypotonia, poor suck, and episodic apnea. One of the patients also had vertical nystagmus as well as cardiac abnormalities, including ventricular septal defect and severe progressive hypertrophic obstructive cardiomyopathy. The patients showed little developmental progress. Brain imaging showed progressive generalized atrophy of the cerebrum, brainstem, and cerebellum, thinning of the corpus callosum, and T2-weighted hyperintensities in the basal ganglia, consistent with a clinical diagnosis of Leigh syndrome. Laboratory studies revealed increased serum and cerebrospinal fluid lactate, and both patients had decreased activities of the pyruvate dehydrogenase complex (PDC). Skeletal muscle biopsy of 1 of the patients showed normal activities of mitochondrial respiratory chain enzymes. Urinary analysis showed increased levels of S-(2-carboxypropyl)cysteine, suggesting a defect in the valine catabolic pathway. The patients also had increased levels of 2-methyl-2,3-dihydroxybutyrate. Additional studies showed normal levels of 3-hydroxyisobutyryl-carnitine, suggesting a defect in ECHS1 rather than HIBCH (610690); sequencing of the HIBCH gene did not reveal any pathogenic mutations. </p><p>Sakai et al. (2015) reported a 4-year-old boy, born of unrelated parents, with a severe neurologic disorder apparent since early infancy. He had delayed psychomotor development with inability to sit unsupported as well as absence of speech, hearing impairment, nystagmus, hypotonia, spasticity, and athetotic movements. Brain imaging showed T2-weighted hyperintensities consistent with Leigh syndrome. Laboratory studies showed increased lactate and increased urinary glyoxylate. Skeletal muscle samples showed a combined deficiency of the activities of mitochondrial respiratory enzymes, including complex I (39% of controls), complex III (34% of controls), and complex IV (64% of controls), although electrophoresis studies showed that assembly of these complexes was normal. </p><p>Yamada et al. (2015) reported a 7-year-old girl and her 5-year-old brother with ECHS1D, who were born of unrelated Japanese parents. Both sibs presented with dystonia between 7 and 10 months of age, after which regression of psychomotor development became apparent. Brain imaging showed T2-weighted hyperintensities in the putamen, globus pallidus, caudate nucleus, and substantia nigra. At examination, both patients bent backward forcefully and had no language. Neither patient had seizures. The condition worsened with viral infection, resulting in death in the 5-year-old boy. Analysis of mitochondrial respiratory chain activities was normal in the fibroblasts of the older sister, and blood and cerebrospinal fluid lactate were not increased, but urinary lactate was increased. There was also increased urinary N-acetyl-S-cysteine, a metabolite of methacrylyl-CoA, and mildly increased 2,3-dihydroxy-2-methylbutyrate. Yamada et al. (2015) concluded that the patients had a relatively milder form of ECHS1D with defective valine catabolic and beta-oxidation pathways, and suggested that N-acetyl-S-cysteine would be a good candidate metabolic marker for the disorder. </p><p>Haack et al. (2015) reported 10 unrelated individuals who presented with a combination of mitochondrial encephalopathy, deafness, epilepsy, optic nerve atrophy, and cardiomyopathy. Brain MRIs were performed in 9 patients and showed white matter changes in 5 early-onset, severely affected patients, and bilateral T2 hyperintensities in the basal ganglia in 4 less severely affected patients. MR spectroscopy of the basal ganglia showed elevated lactate in 3 of 7 individuals. 2-Methyl-2,3,-dihydroxybutyrate was elevated in the urine of 3 of 4 patients tested, and higher levels appeared to correlate with severe disease expression. Four patients died before the age of 7.5 (range, 4 months to 7.5 years) and 6 patients were alive at the time of reporting (range, 2-31 years). Analysis of enzymes involved in oxidative phosphorylation in muscle tissue and/or fibroblasts showed mild and inconsistent changes in 4 of 8 patients tested, including abnormalities in pyruvate oxidation or ATP production and decreased activity of complex I or complex IV, in 1 patient each. </p><p>Tetreault et al. (2015) reported 4 patients from 3 apparently unrelated French Canadian families who had developmental regression in early infancy, failure to thrive, and nystagmus. Three patients had optic atrophy and sensorineural hearing loss. Three patients had episodic neurologic changes, and in 2 the changes were in the context of viral infections. All 4 patients had brain MRI abnormalities including T2 weighted hyperintensities of the basal ganglia. MRS showed a lactate peak in 1 patient. Studies in patient fibroblasts showed normal pyruvate dehydrogenase activity in 2 patients and slightly decreased pyruvate dehydrogenase activity in 1 patient. Cytochrome c oxidase and succinate cytochrome c reductase activity was normal in fibroblasts from all patients. Respiratory chain studies in muscle showed a slight reduction in complex I and complex III activity in 1 patient, and normal activity in the other 3 patients. </p><p>Fitzsimons et al. (2018) reported 4 patients with ECHS1D, 3 of whom were sibs. Age range of clinical presentation was 2 weeks to 5 months. All 4 patients had elevated erythro-2,3-dihydroxy-2-methylbutyrate and 3-methylglutaconic acid on urine organic acids. In 2 patients, analysis of urine metabolites showed elevated acryloyl cysteamine, N-acetyl-acryloyl-cysteine, methacryl-L-cysteine, and N-acetyl-methacryl-cysteine. All patients also had at least one elevated plasma lactate measurement. MRIs in all patients showed abnormal signal in the bilateral basal ganglia. In 2 patients, prominent sulci and volume loss were noted. In 1 patient there was thinning of the corpus callosum and cerebral and cerebellar atrophy. Three patients had a lactate peak on MRS, and 3 patients had seizures. All patients had developmental delay with regression, and all required feeding support for poor weight gain, 1 via nasogastric tube and 3 via PEG tube. All patients were deceased, with age of death ranging from 13 months to 4 years. </p>
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</span>
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<div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Inheritance</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The transmission pattern of ECHS1D in the family reported by Peters et al. (2014) was consistent with autosomal recessive inheritance. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In 2 sibs with ECHS1D, Peters et al. (2014) identified compound heterozygous mutations in the ECHS1 gene (A158D, 602292.0001 and c.414+3G-C, 602292.0002). Patient fibroblasts showed significantly decreased ECHS1 activity and absence of the normal protein by immunoblot analysis. Peters et al. (2014) postulated that the enzymatic defect caused accumulation of the metabolites methacrylyl-CoA and acryloyl-CoA, which are toxic reactive intermediates that may have caused the brain pathology. Decreased activity of the PDC may also have been a secondary effect. The metabolic abnormalities in these patients appeared to be confined to the valine pathway, since fatty acid and isoleucine metabolites were normal. </p><p>In a boy with ECHS1D, Sakai et al. (2015) identified compound heterozygous mutations in the ECHS1 gene (M1R, 602292.0003 and A2V, 602292.0004). The mutations, which were found by targeted exome sequencing, segregated with the disorder in the family. Patient cells also showed a combined mitochondrial respiratory chain deficiency, which was rescued by expression of wildtype ECHS1. These findings suggested a link between ECHS1 and the mitochondrial respiratory chain. Sakai et al. (2015) speculated that ECHS1 deficiency induced metabolic abnormalities resulting in the accumulation of toxic metabolites, such as glyoxylate, that secondarily inhibited normal mitochondrial respiratory function. </p><p>In 2 sibs, born of unrelated Japanese parents, with ECHS1D, Yamada et al. (2015) identified compound heterozygous missense mutations in the ECHS1 gene (N59S, 602292.0005 and A138V, 602292.0006). The mutations, which were found by a combination of linkage analysis and whole-exome sequencing, segregated with the disorder in the family. ECHS1 activity towards different substrates was decreased to between 2.6% and 6.2% of normal controls. In vitro functional expression studies showed that the D59S mutant was nonfunctional, whereas the A138V mutant had about 30% residual activity. </p><p>In 10 unrelated families segregating ECHS1D, Haack et al. (2015) identified homozygous or compound heterozygous mutations in the ECHS1 gene. In 1 family (F3), 3 affected sibs (proband 68552), born to consanguineous Pakistani parents, were homozygous for a missense mutation (Q159R; 602292.0007). In 2 unrelated families (F1 and F10), patient 346 and patient 52236 were compound heterozygous for the Q159R mutation and different second mutations (N59S, 602292.0008 and E77Q, 602292.0009), respectively. The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. Immunoblotting on fibroblasts from the 2 compound heterozygous patients showed reduced expression of the ECHS1 protein and reduced palmitate-dependent respiration; fibroblasts from 1 of these patients showed reduced 2-enoyl-CoA hydratase activity. </p><p>In 4 patients with ECHS1D from 3 unrelated French Canadian families, Tetreault et al. (2015) identified compound heterozygous mutations in the ECHS1 gene. All 3 had a T180A missense mutation (602292.0010) with a different second mutation (see, e.g., 602292.0011 and 602292.0012). All of the mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing. All 4 mutations occurred in the ECHS1 enoyl-CoA hydratase/isomerase domain and were predicted to decrease protein stability. </p><p>In 3 Irish Traveler sibs and a Pakistani patient with ECHS1D, Fitzsimons et al. (2018) identified homozygosity for the previously identified T180A and Q159R mutations in the ECHS1 gene, respectively. Erythro-2,3-dihydroxy-2-methylbutyrate and 3-methylglutaconic acid were elevated on urine organic acids of all patients. Muscle and fibroblast testing was carried out in 1 sib and the Pakistani patient. Fibroblasts showed markedly decreased ECHS1 enzyme activity and absence of ECHS1 on Western blot analysis. PDH activity and beta oxidation studies were normal. Activities of respiratory chain complexes I, II, and IV were normal, and activity of complexes II+III was decreased in muscle. </p><p>In 4 patients, including 3 sibs, from 2 families with Samoan heritage with ECHS1D, Simon et al. (2021) identified compound heterozygous mutations in the ECHS1 gene (A278T, 602292.0012 and P163P, 602292.0013). ECHS1 protein expression and activity were reduced in fibroblasts from the carrier parents from family 1 and reduced to a greater degree in their affected offspring. ECHS1 protein expression and activity were also reduced in fibroblasts from the patient in family 2. Analysis of mRNA in fibroblasts from the unaffected Samoan mother from family 1, who was homozygous for the P163P variant, and from one of her affected children demonstrated that the P163P variant resulted in abnormal splicing with skipping of exon 4. Family 1 was previously reported by Abdenur et al. (2020). </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Population Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Simon et al. (2021) identified a synonymous P163P variant in the ECHS1 gene (602292.0013) at an allele frequency of 0.17 in the Samoan population, with 34 homozygotes detected. This frequency did not suggest decreased fitness in individuals with homozygosity for the variant; however, Simon et al. (2021) found the variant to be disease causing when in trans with a severe mutation on the other ECHS1 allele. </p>
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</span>
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<div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Abdenur, J. E., Sowa, M., Simon, M., Steenari, M., Skaar, J., Eftekharian, S., Chang, R., Ferdinandusse, S., Pitt, J.
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<strong>Medical nutrition therapy in patients with HIBCH and ECHS1 defects: clinical and biochemical response to low valine diet.</strong>
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Molec. Genet. Metab. Rep. 24: 100617, 2020.
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[PubMed: 32642440]
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[Full Text: https://doi.org/10.1016/j.ymgmr.2020.100617]
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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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Fitzsimons, P. E., Alston, C. L., Bonnen, P. E., Hughes, J., Crushell, E., Geraghty, M. T., Tetreault, M., O'Reilly, P., Twomey, E., Sheikh, Y., Walsh, R., Waterham, H. R., Ferdinandusse, S., Wanders, R. J. A., Taylor, R. W., Pitt, J. J., Mayne, P. D.
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<strong>Clinical, biochemical, and genetic features of four patients with short-chain enoyl-CoA hydratase (ECHS1) deficiency.</strong>
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Am. J. Med. Genet. 176A: 1115-1127, 2018.
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[PubMed: 29575569]
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[Full Text: https://doi.org/10.1002/ajmg.a.38658]
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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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Haack, T. B., Jackson, C. B., Murayama, K., Kremer, L. S., Schaller, A., Kotzaeridou, U., de Vries, M. C., Schottmann, G., Santra, S., Buchner, B., Wieland, T., Graf, E., and 28 others.
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<strong>Deficiency of ECHS1 causes mitochondrial encephalopathy with cardiac involvement.</strong>
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Ann. Clin. Transl. Neurol. 2: 492-509, 2015.
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[PubMed: 26000322]
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[Full Text: https://doi.org/10.1002/acn3.189]
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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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Peters, H., Buck, N., Wanders, R., Ruiter, J., Waterham, H., Koster, J., Yaplito-Lee, J., Ferdinandusse, S., Pitt, J.
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<strong>ECHS1 mutations in Leigh disease: a new inborn error of metabolism affecting valine metabolism.</strong>
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Brain 137: 2903-2908, 2014.
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[PubMed: 25125611]
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[Full Text: https://doi.org/10.1093/brain/awu216]
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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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Sakai, C., Yamaguchi, S., Sasaki, M., Miyamoto, Y., Matsushima, Y., Goto, Y.
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<strong>ECHS1 mutations cause combined respiratory chain deficiency resulting in Leigh syndrome.</strong>
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Hum. Mutat. 36: 232-239, 2015.
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[PubMed: 25393721]
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[Full Text: https://doi.org/10.1002/humu.22730]
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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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Simon, M. T., Eftekharian, S. S., Ferdinandusse, S., Tang, S., Naseri, T., Reupena, M. S., McGarvey, S. T., Minster, R. L., Weeks, D. E., Samoan Obesity, Lifestyle, and Genetic Adaptations (OLaGA) Study Group, Nguyen, D. D., Lee, S., Ellsworth, K. A., Vaz, F. M., Dimmock, D., Pitt, J., Abdenur, J. E.
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<strong>ECHS1 disease in two unrelated families of Samoan descent: common variant--rare disorder.</strong>
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Am. J. Med. Genet. 185A: 157-167, 2021.
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[PubMed: 33112498]
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[Full Text: https://doi.org/10.1002/ajmg.a.61936]
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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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Tetreault, M., Fahiminiya, S., Antonicka, H., Mitchell, G. A., Geraghty, M. T., Lines, M., Boycott, K. M., Shoubridge, E. A., Mitchell, J. J., Care4Rare Canada Consortium, Michaud, J. L., Majewski, J.
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<strong>Whole-exome sequencing identifies novel ECHS1 mutations in Leigh syndrome.</strong>
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Hum. Genet. 134: 981-991, 2015.
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[PubMed: 26099313]
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[Full Text: https://doi.org/10.1007/s00439-015-1577-y]
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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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Yamada, K., Aiba, K., Kitaura, Y., Kondo, Y., Nomura, N., Nakamura, Y., Fukushi, D., Murayama, K., Shimomura, Y., Pitt, J., Yamaguchi, S., Yokochi, K., Wakamatsu, N.
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<strong>Clinical, biochemical and metabolic characterisation of a mild form of human short-chain enoyl-CoA hydratase deficiency: significance of increased N-acetyl-S-(2-carboxypropyl)cysteine excretion.</strong>
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J. Med. Genet. 52: 691-698, 2015.
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[PubMed: 26251176]
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[Full Text: https://doi.org/10.1136/jmedgenet-2015-103231]
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</li>
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<div>
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<div class="row">
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Contributors:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 08/05/2024<br>Hilary J. Vernon - updated : 07/13/2020<br>Cassandra L. Kniffin - updated : 12/21/2015
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</span>
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin : 3/23/2015
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</span>
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<div>
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