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<title>
Entry
- #614739 - 3-METHYLGLUTACONIC ACIDURIA WITH DEAFNESS, ENCEPHALOPATHY, AND LEIGH-LIKE SYNDROME; MEGDEL
- OMIM
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<span class="h4">#614739</span>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/614739"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS250950"> <strong>Phenotypic Series</strong> </a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#populationGenetics">Population Genetics</a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=3-METHYLGLUTACONIC ACIDURIA WITH DEAFNESS, ENCEPHALOPATHY, AND LEIGH-LIKE SYNDROME" 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.alliancegenome.org/disease/DOID:0110001" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
<div><a href="http://www.informatics.jax.org/disease/614739" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
<div><a href="https://omia.org/OMIA001468/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
<div><a href="https://wormbase.org/resources/disease/DOID:0110001" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
</div>
</div>
</div>
</div>
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</div>
<span>
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
&nbsp;
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>SNOMEDCT:</strong> 711409002<br />
<strong>ORPHA:</strong> 352328<br />
<strong>DO:</strong> 0110001<br />
">ICD+</a>
</div>
<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
614739
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
3-METHYLGLUTACONIC ACIDURIA WITH DEAFNESS, ENCEPHALOPATHY, AND LEIGH-LIKE SYNDROME; MEGDEL
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<a id="alternativeTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
3-METHYLGLUTACONIC ACIDURIA WITH DYSTONIA-DEAFNESS, HEPATOPATHY, ENCEPHALOPATHY, AND LEIGH-LIKE SYNDROME; MEGDHEL<br />
3-METHYLGLUTACONIC ACIDURIA, TYPE VI; MGCA6
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/982?start=-3&limit=10&highlight=982">
6q25.3
</a>
</span>
</td>
<td>
<span class="mim-font">
3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614739"> 614739 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
SERAC1
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614725"> 614725 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/614739" class="btn btn-warning" role="button"> Clinical Synopsis </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
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<span class="sr-only">Toggle Dropdown</span>
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&nbsp;
<div class="btn-group">
<a href="/phenotypicSeries/PS250950" class="btn btn-info" role="button"> Phenotypic Series </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
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&nbsp;
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
</button>
<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/614739" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/614739" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
</ul>
</div>
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GROWTH </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Other </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Failure to thrive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/432788009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">432788009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/54840006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">54840006</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0015544&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015544</a>, <a href="https://bioportal.bioontology.org/search?q=C2315100&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2315100</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Head </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Microcephaly (1 patient) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1148757008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1148757008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q02" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q02</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/742.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">742.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551563&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551563</a>, <a href="https://bioportal.bioontology.org/search?q=C0025958&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025958</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Microcephaly-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Ears </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hearing loss, sensorineural <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/60700002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">60700002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H90.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H90.5</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/389.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.10</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/389.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018784&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018784</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000407" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000407</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000407" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000407</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Optic atrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/76976005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">76976005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.2</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.20</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/377.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.10</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/377.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0029124&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029124</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Mouth </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Oropharyngeal dyskinesia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4693188&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4693188</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ABDOMEN </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Liver </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hepatic dysfunction, neonatal period (48%) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4693186&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4693186</a>]</span><br /> -
Liver failure, neonatal period (in some patients), reversible<br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Gastrointestinal </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Feeding problems <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/274540003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">274540003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/78164000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">78164000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R63.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R63.3</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0232466&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0232466</a>, <a href="https://bioportal.bioontology.org/search?q=C0699815&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0699815</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> 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 /> -
Degrading mitochondria <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3553598&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3553598</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> NEUROLOGIC </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Central Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Psychomotor retardation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398991009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398991009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1144814003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1144814003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0424230&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424230</a>, <a href="https://bioportal.bioontology.org/search?q=C5441816&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5441816</a>]</span><br /> -
Psychomotor regression <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855019&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855019</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002376" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002376</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002376" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002376</a>]</span><br /> -
Mental retardation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/228156007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">228156007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/110359009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">110359009</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/317-319.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">317-319.99</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714756&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714756</a>, <a href="https://bioportal.bioontology.org/search?q=C0025362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span><br /> -
Spasticity <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 /> -
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 /> -
Extrapyramidal symptoms <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/43378000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">43378000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234133&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234133</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002071" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002071</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002071" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002071</a>]</span><br /> -
Inability to walk <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/282145008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">282145008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0560046&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0560046</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002540" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002540</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002540" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002540</a>]</span><br /> -
Poor or absent speech <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3278212&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3278212</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000750" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000750</a>]</span><br /> -
Seizures (less common) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91175000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91175000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span><br /> -
Leigh syndrome <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/29570005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">29570005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G31.82" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G31.82</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0023264&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023264</a>]</span><br /> -
Lesions in the basal ganglia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1389273&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1389273</a>]</span><br /> -
Brain atrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/278849000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">278849000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551584&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551584</a>, <a href="https://bioportal.bioontology.org/search?q=C0235946&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0235946</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012444" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012444</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0002059" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002059</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012444" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012444</a>]</span><br /> -
Cerebellar atrophy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0740279&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0740279</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001272" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001272</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001272" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001272</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> METABOLIC FEATURES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Lactic acidosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91273001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91273001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E87.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E87.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0001125&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0001125</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003128" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003128</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003128" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003128</a>]</span><br /> -
Hypoglycemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237630007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237630007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/271327008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">271327008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/302866003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">302866003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1179458001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1179458001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E16.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E16.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/251.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">251.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020615&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020615</a>, <a href="https://bioportal.bioontology.org/search?q=C5767385&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5767385</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001943" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001943</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001943" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001943</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> IMMUNOLOGY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Recurrent infections <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/451991000124106" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">451991000124106</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0239998&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239998</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002719" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002719</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002719" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002719</a>]</span><br /> -
Neonatal sepsis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/276669000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">276669000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/206376005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">206376005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/P36" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">P36</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/P36.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">P36.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0456103&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0456103</a>, <a href="https://bioportal.bioontology.org/search?q=C3665339&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3665339</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0040187" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0040187</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0040187" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0040187</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- 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 /> -
Defects in mitochondrial oxidative phosphorylation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3553599&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3553599</a>]</span><br /> -
3-methylglutaconic aciduria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237950009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237950009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E71.111" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E71.111</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3696376&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3696376</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003535" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003535</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003535" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003535</a>]</span><br /> -
Abnormal phospholipid profile <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3553600&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3553600</a>]</span><br /> -
Abnormal phosphatidylglycerol profile (increased 34-to-1 and decreased 36-to-1 ratio) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3808570&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3808570</a>]</span><br /> -
Abnormal cardiolipin subspecies composition <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3553602&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3553602</a>]</span><br /> -
Intracellular accumulation of unesterified cholesterol <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3553603&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3553603</a>]</span><br /> -
Decreased serum cholesterol (in some) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4325587&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4325587</a>]</span><br /> -
Elevated serum transaminase levels <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3808571&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3808571</a>]</span><br /> -
Hyperammonemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/9360008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">9360008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E72.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E72.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5574662&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5574662</a>, <a href="https://bioportal.bioontology.org/search?q=C0220994&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0220994</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001987" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001987</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001987" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001987</a>]</span><br /> -
Elevated serum alpha-fetoprotein <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3808572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3808572</a>]</span><br /> -
Coagulopathy (INR = 2.2 - 3.5) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3808573&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3808573</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/64779008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">64779008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/362970003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">362970003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D68.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D68.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/286" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">286</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003256" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003256</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Onset in infancy or early childhood<br /> -
There are estimated to be 27 affected children born worldwide each year<br /> -
Variable severity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1861403&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1861403</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003828" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003828</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003828" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003828</a>]</span><br /> -
One family with a milder disorder without deafness has been reported (last curated February 2018)<br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Caused by mutation in the serine active site-containing protein 1 (SERAC1, <a href="/entry/614725#0001">614725.0001</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
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<div class="small">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<h5>
3-Methylglutaconic aciduria
- <a href="/phenotypicSeries/PS250950">PS250950</a>
- 9 Entries
</h5>
</div>
</div>
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
<table class="table table-bordered table-condensed table-hover mim-table-padding">
<thead>
<tr>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Location</strong>
</th>
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
<strong>Phenotype</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Inheritance</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />mapping key</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />MIM number</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus<br />MIM number</strong>
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/389?start=-3&limit=10&highlight=389"> 2p13.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617248"> 3-methylglutaconic aciduria, type VIII </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617248"> 617248 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606441"> HTRA2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606441"> 606441 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/888?start=-3&limit=10&highlight=888"> 3q26.33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610198"> 3-methylglutaconic aciduria, type V </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610198"> 610198 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608977"> DNAJC19 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608977"> 608977 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/982?start=-3&limit=10&highlight=982"> 6q25.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614739"> 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614739"> 614739 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614725"> SERAC1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614725"> 614725 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/9/298?start=-3&limit=10&highlight=298"> 9q22.31 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/250950"> 3-methylglutaconic aciduria, type I </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/250950"> 250950 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600529"> AUH </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600529"> 600529 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/722?start=-3&limit=10&highlight=722"> 11q13.4 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616271"> 3-methylglutaconic aciduria, type VIIB, autosomal recessive </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616271"> 616271 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616254"> CLPB </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616254"> 616254 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/684?start=-3&limit=10&highlight=684"> 19q13.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617698"> 3-methylglutaconic aciduria, type IX </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617698"> 617698 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607381"> TIMM50 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607381"> 607381 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/826?start=-3&limit=10&highlight=826"> 19q13.32 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/258501"> 3-methylglutaconic aciduria, type III </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/258501"> 258501 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606580"> OPA3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606580"> 606580 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/X/861?start=-3&limit=10&highlight=861"> Xq28 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/302060"> Barth syndrome </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/302060"> 302060 </a>
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<a href="/entry/250951"> 3-methylglutaconic aciduria, type IV </a>
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<a href="/entry/250951"> MGCA1 </a>
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<a href="/entry/250951"> 250951 </a>
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<p>A number sign (#) is used with this entry because 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (MEGDEL), also referred to as 3-methylglutaconic aciduria type VI (MGCA6), is caused by homozygous or compound heterozygous mutation in the SERAC1 gene (<a href="/entry/614725">614725</a>) on chromosome 6q25.</p>
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<p>MEGDEL is an autosomal recessive disorder characterized by childhood onset of delayed psychomotor development or psychomotor regression, sensorineural deafness, spasticity or dystonia, and increased excretion of 3-methylglutaconic acid. Brain imaging shows cerebral and cerebellar atrophy as well as lesions in the basal ganglia reminiscent of Leigh syndrome (<a href="/entry/256000">256000</a>). Laboratory studies show increased serum lactate and alanine, mitochondrial oxidative phosphorylation defects, abnormal mitochondria, abnormal phosphatidylglycerol and cardiolipin profiles in fibroblasts, and abnormal accumulation of unesterified cholesterol within cells (summary by <a href="#8" class="mim-tip-reference" title="Wortmann, S. B., Vaz, F. M., Gardeitchik, T., Vissers, L. E. L. M., Renkema, G. H., Schuurs-Hoeijmakers, J. H. M., Kulik, W., Lammens, M., Christin, C., Kluijtmans, L. A. J., Rodenburg, R. J., Nijtmans, L. G. J., and 22 others. &lt;strong&gt;Mutations in the phospholipid remodeling gene SERCA1 impair mitochondrial function and intracellular cholesterol trafficking and cause dystonia and deafness.&lt;/strong&gt; Nature Genet. 44: 797-802, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22683713/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22683713&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng.2325&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22683713">Wortmann et al., 2012</a>). About 50% of patients develop severe, but transient, liver dysfunction and/or signs of liver failure, in the neonatal period or during the first year of life, prompting some authors to suggest the name 'MEGDHEL' syndrome, with the 'H' referring to 'hepatopathy' (summary by <a href="#2" class="mim-tip-reference" title="Maas, R. R., Iwanicka-Pronicka, K., Kalkan Ucar, S., Alhaddad, B., AlSayed, M., Al-Owain, M. A., Al-Zaidan, H. I., Balasubramaniam, S., Baric, I., Bubshait, D. K., Burlina, A., Christodoulou, J., and 46 others. &lt;strong&gt;Progressive deafness-dystonia due to SERAC1 mutations: a study of 67 cases.&lt;/strong&gt; Ann. Neurol. 82: 1004-1015, 2017.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29205472/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;29205472&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=29205472[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.25110&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="29205472">Maas et al., 2017</a>). Some patients may have a milder presentation with juvenile-onset spasticity and mild cognitive impairment, indicating a broader phenotypic spectrum (<a href="#4" class="mim-tip-reference" title="Roeben, B., Schule, R., Ruf, S., Bender, B., Alhaddad, B., Benkert, T., Meitinger, T., Reich, S., Bohringer, J., Langhans, C.-D., Vaz, F. M., Wortmann, S. B., Marquart, T., Haack, T. B., Krageloh-Mann, I., Schols, L., Synofzik, M. &lt;strong&gt;SERAC1 deficiency causes complicated HSP: evidence from a novel splice mutation in a large family.&lt;/strong&gt; J. Med. Genet. 55: 39-47, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/28916646/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;28916646&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmedgenet-2017-104622&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="28916646">Roeben et al., 2018</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=28916646+22683713+29205472" 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>For a general phenotypic description and a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA type I (<a href="/entry/250950">250950</a>).</p>
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<p>Wortmann et al. (<a href="#9" class="mim-tip-reference" title="Wortmann, S., Rodenburg, R. J. T., Huizing, M., Loupatty, F. J., de Koning, T., Kluijtmans, L. A. J., Engelke, U., Wevers, R., Smeitink, J. A. M., Morava, E. &lt;strong&gt;Association of 3-methylglutaconic aciduria with sensori-neural deafness, encephalopathy, and Leigh-like syndrome (MEGDEL association) in four patients with a disorder of the oxidative phosphorylation.&lt;/strong&gt; Molec. Genet. Metab. 88: 47-52, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16527507/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16527507&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2006.01.013&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16527507">2006</a>, <a href="#7" class="mim-tip-reference" title="Wortmann, S. B., Rodenburg, R. J. T., Jonckheere, A., de Vries, M. C., Huizing, M., Heldt, K., van den Heuvel, L. P., Wendel, U., Kluijtmans, L. A., Engelke, U. F., Wevers, R. A., Smeitink, J. A. M., Morava, E. &lt;strong&gt;Biochemical and genetic analysis of 3-methylglutaconic aciduria type IV: a diagnostic strategy.&lt;/strong&gt; Brain 132: 136-146, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19015156/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19015156&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/brain/awn296&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19015156">2009</a>) reported 4 unrelated girls with an encephalomyopathy associated with mildly and intermittently increased urinary 3-methylglutaconic aciduria. Three children were born of 3 unrelated sets of consanguineous Turkish parents, and the fourth child was born of unrelated Dutch parents. All presented in the neonatal period with severe infections and had episodes of lactic acidosis and hypoglycemia. Other features included failure to thrive, loss of motor skills, mental retardation, sensorineural deafness, and hypotonia with progressive spasticity. One patient had delayed development, 1 did not develop at all, and the other 2 showed developmental regression during early childhood. Brain MRI showed cerebral and cerebellar atrophy as well as bilateral hyperintensities in the basal ganglia reminiscent of Leigh syndrome. Mitochondrial complex I deficiency was found in muscle and fibroblasts. Two patients died at age 3 and 16 years, respectively. Genetic analysis did not find mutations in several candidate genes. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19015156+16527507" 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="Wortmann, S. B., Vaz, F. M., Gardeitchik, T., Vissers, L. E. L. M., Renkema, G. H., Schuurs-Hoeijmakers, J. H. M., Kulik, W., Lammens, M., Christin, C., Kluijtmans, L. A. J., Rodenburg, R. J., Nijtmans, L. G. J., and 22 others. &lt;strong&gt;Mutations in the phospholipid remodeling gene SERCA1 impair mitochondrial function and intracellular cholesterol trafficking and cause dystonia and deafness.&lt;/strong&gt; Nature Genet. 44: 797-802, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22683713/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22683713&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng.2325&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22683713">Wortmann et al. (2012)</a> reported 11 additional patients with MEGDEL, including 2 relatives of 1 of the Turkish patients reported by <a href="#9" class="mim-tip-reference" title="Wortmann, S., Rodenburg, R. J. T., Huizing, M., Loupatty, F. J., de Koning, T., Kluijtmans, L. A. J., Engelke, U., Wevers, R., Smeitink, J. A. M., Morava, E. &lt;strong&gt;Association of 3-methylglutaconic aciduria with sensori-neural deafness, encephalopathy, and Leigh-like syndrome (MEGDEL association) in four patients with a disorder of the oxidative phosphorylation.&lt;/strong&gt; Molec. Genet. Metab. 88: 47-52, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16527507/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16527507&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2006.01.013&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16527507">Wortmann et al. (2006)</a>. The phenotype was relatively homogeneous, with psychomotor retardation, spasticity or dystonia, sensorineural deafness, Leigh syndrome-like lesions on brain imaging, and brain atrophy. Laboratory studies showed 3-methylglutaconic aciduria, increased serum lactate, and defects in oxidative phosphorylation. Patient fibroblasts showed an increased phosphatidylglycerol 34:1 to phosphatidylglycerol 36:1 ratio as well as abnormal cardiolipin subspecies. There was abnormal intracellular accumulation of unesterified cholesterol, and some patients had low serum cholesterol. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=22683713+16527507" 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="Sarig, O., Goldsher, D., Nousbeck, J., Fuchs-Telem, D., Cohen-Katsenelson, K., Iancu, T. C., Manov, I., Saada, A., Sprecher, E., Mandel, H. &lt;strong&gt;Infantile mitochondrial hepatopathy is a cardinal feature of MEGDEL syndrome (3-methylglutaconic aciduria type IV with sensorineural deafness, encephalopathy and Leigh-like syndrome) caused by novel mutations in SERAC1.&lt;/strong&gt; Am. J. Med. Genet. 161A: 2204-2215, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23918762/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;23918762&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.36059&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="23918762">Sarig et al. (2013)</a> reported 4 males, 2 each from 2 unrelated, highly consanguineous families, with features consistent with MEGDEL syndrome, including 3-methylglutaconic aciduria, sensorineural deafness, encephalopathy, and brain magnetic resonance imaging with findings consistent with Leigh-like syndrome. All 4 patients presented at age 24 to 48 hours with hypotonia and evidence of liver dysfunction, including symptomatic hypoglycemia, lactic acidosis, elevated serum transaminase levels, coagulopathy, hyperammonemia, and markedly elevated serum alpha-fetoprotein. During periods of acute infection in the first year of life, the patients experienced a few episodes of liver dysfunction, but these episodes did not recur later in life. Electron microscopy of a liver biopsy from 1 patient showed hepatocyte steatosis with mitochondrial ultrastructural changes, consistent with a mitochondrial oxidative phosphorylation disorder and abnormal lipid metabolism. The patients subsequently developed features of MEGDEL syndrome. The families were found to have 2 homozygous mutations in the SERAC1 gene that led to decreased or absent gene expression. <a href="#5" class="mim-tip-reference" title="Sarig, O., Goldsher, D., Nousbeck, J., Fuchs-Telem, D., Cohen-Katsenelson, K., Iancu, T. C., Manov, I., Saada, A., Sprecher, E., Mandel, H. &lt;strong&gt;Infantile mitochondrial hepatopathy is a cardinal feature of MEGDEL syndrome (3-methylglutaconic aciduria type IV with sensorineural deafness, encephalopathy and Leigh-like syndrome) caused by novel mutations in SERAC1.&lt;/strong&gt; Am. J. Med. Genet. 161A: 2204-2215, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23918762/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;23918762&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.36059&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="23918762">Sarig et al. (2013)</a> suggested that neonatal liver disease is a component of the phenotypic spectrum of MEGDEL syndrome and proposed that the disease be renamed MEGDHEL syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23918762" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Tort, F., Garcia-Silva, M. T., Ferrer-Cortes, X., Navarro-Sastre, A., Garcia-Villoria, J., Coll, M. J., Vidal, E., Jimenez-Almazan, J., Dopazo, J., Briones, P., Elpeleg, O., Ribes, A. &lt;strong&gt;Exome sequencing identifies a new mutation in SERAC1 in a patient with 3-methylglutaconic aciduria.&lt;/strong&gt; Molec. Genet. Metab. 110: 73-77, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23707711/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;23707711&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2013.04.021&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="23707711">Tort et al. (2013)</a> reported a girl, born of unrelated parents, with MEGDEL. She presented on the fourth day of life with respiratory distress, refusal to feed, and jaundice, and was found to have metabolic acidosis with ketonuria, hyperammonemia, and elevated liver enzymes. During the first few years of life, she developed oral dyskinesia, hypotonia, truncal ataxia, episodic ketotic hypoglycemia, and psychomotor deterioration. Brain imaging showed features typical of Leigh syndrome. Urinary analysis showed 3-methylglutaconic and 3-methylglutaric aciduria. Sensorineural deafness and optic atrophy became apparent in her teenage years. At age 19 years, she was severely affected, with microcephaly, poor communication skills, inability to hold up her head, and multiple joint problems. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23707711" 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="Maas, R. R., Iwanicka-Pronicka, K., Kalkan Ucar, S., Alhaddad, B., AlSayed, M., Al-Owain, M. A., Al-Zaidan, H. I., Balasubramaniam, S., Baric, I., Bubshait, D. K., Burlina, A., Christodoulou, J., and 46 others. &lt;strong&gt;Progressive deafness-dystonia due to SERAC1 mutations: a study of 67 cases.&lt;/strong&gt; Ann. Neurol. 82: 1004-1015, 2017.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29205472/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;29205472&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=29205472[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.25110&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="29205472">Maas et al. (2017)</a> reviewed the clinical features of 67 patients with MEGDEL, including 39 previously unreported individuals. Most (64%) of the families were consanguineous. Most of the individuals were of European ancestry, although several dozen patients were from Africa, Asia, the Middle East, or Australia, indicating that MEGDEL is a panethnic disorder. With the exception of 2 families with a milder phenotype and onset later in childhood, all affected individuals showed a strikingly homogeneous phenotype and time course. Sixteen patients died at a median age of 9 years, mostly due to respiratory infections. In the neonatal period, 48% of patients showed liver dysfunction and hypoglycemia, with variable abnormal liver enzymes, increased bilirubin, and disturbed coagulation in the more severe cases. Signs of hepatic dysfunction during the first year of life were common in this group, but resolved afterwards. Other presenting symptoms of the disorder included neonatal sepsis, hypotonia, and delayed motor development. The majority of patients lost previously acquired skills in the first year of life. Patients had early-onset progressive spasticity, dystonia, and oropharyngeal dyskinesia, and most (78%) never learned to walk. All had intellectual disability that varied from mild (12%) to severe (73%), and nearly all (93%) were completely dependent for activities of daily living. Additional features included epilepsy (35%), sensorineural hearing impairment (79%), absent speech (58%), impaired vision (42%), retinal pigmentary changes (6%), optic atrophy (25%), recurrent respiratory infections (42%), scoliosis (39%), and poor feeding (79%), often necessitating tube feeding. Less common features included transient renal tubular dysfunction (12%) and cardiac abnormalities (7%). Laboratory studies showed increased urinary 3-MGA and increased serum lactate, and brain imaging showed lesions in the basal ganglia, consistent with Leigh syndrome. <a href="#2" class="mim-tip-reference" title="Maas, R. R., Iwanicka-Pronicka, K., Kalkan Ucar, S., Alhaddad, B., AlSayed, M., Al-Owain, M. A., Al-Zaidan, H. I., Balasubramaniam, S., Baric, I., Bubshait, D. K., Burlina, A., Christodoulou, J., and 46 others. &lt;strong&gt;Progressive deafness-dystonia due to SERAC1 mutations: a study of 67 cases.&lt;/strong&gt; Ann. Neurol. 82: 1004-1015, 2017.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29205472/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;29205472&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=29205472[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.25110&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="29205472">Maas et al. (2017)</a> concluded that MEGDEL is best classified as a disorder of the biosynthesis of complex lipids with secondary mitochondrial dysfunction, although MEGDEL syndrome displays typical findings and the progressive course of a mitochondrial disorder. However, mitochondrial dysfunction in tissue varies greatly and may be unremarkable. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29205472" 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="Radha Rama Devi, A. R., Lingappa, L. &lt;strong&gt;Novel mutations in SERAC1 gene in two Indian patients presenting with dystonia and intellectual disability.&lt;/strong&gt; Europ. J. Med. Genet. 61: 100-103, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/28778788/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;28778788&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ejmg.2017.07.013&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="28778788">Radha Rama Devi and Lingappa (2018)</a> reported 2 unrelated Indian patients with MEGDEL. The first patient presented in the neonatal period with respiratory distress, neonatal hepatitis, elevated serum lactate, and metabolic acidosis. At 15 months of age, she had developmental delay and dystonia. At age 7 years she had generalized dystonia, seizures, spasticity, and flexion contractures. Brain MRI showed bilateral abnormal signal in the putamen and caudate. The second patient had normal development until 3 years of age, but then had progressive developmental regression. At age 4 years she had hepatitis, jaundice, and elevated serum lactate. At age 11 years, she had ataxia, severe dystonia, and dysarthria. Brain MRI at age 11 years showed bilateral abnormal signal in the putamen and claustrum. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28778788" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Lumish, H. S., Yang, Y., Xia, F., Wilson, A., Chung, W. K. &lt;strong&gt;The expanding MEGDEL phenotype: optic nerve atrophy, microcephaly, and myoclonic epilepsy in a child with SERAC1 mutations.&lt;/strong&gt; JIMD Rep. 16: 75-79, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24997715/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;24997715&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/8904_2014_322&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="24997715">Lumish et al. (2014)</a> reported a 5-year-old boy with developmental delay, developmental regression, bilateral optic nerve atrophy, microcephaly, sensorineural hearing loss, and myoclonic epilepsy. After birth, he had respiratory distress, an anion gap metabolic acidosis, and mild elevations in liver function tests. His developmental milestones were delayed. He experienced developmental regression at 3 years of age. An EEG at age 22 months was suggestive of partial epilepsy. MRI of the brain at age 22 months showed a Leigh syndrome-like pattern. Follow-up MRIs demonstrated progressive basal ganglia and cerebellar volume loss. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24997715" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Clinical Variability</em></strong></p><p>
<a href="#4" class="mim-tip-reference" title="Roeben, B., Schule, R., Ruf, S., Bender, B., Alhaddad, B., Benkert, T., Meitinger, T., Reich, S., Bohringer, J., Langhans, C.-D., Vaz, F. M., Wortmann, S. B., Marquart, T., Haack, T. B., Krageloh-Mann, I., Schols, L., Synofzik, M. &lt;strong&gt;SERAC1 deficiency causes complicated HSP: evidence from a novel splice mutation in a large family.&lt;/strong&gt; J. Med. Genet. 55: 39-47, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/28916646/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;28916646&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmedgenet-2017-104622&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="28916646">Roeben et al. (2018)</a> reported a large consanguineous Iraqi kindred in which 6 individuals from 2 different family branches had a relatively mild form of MEGDEL, which was characterized by the authors as 'juvenile-onset complicated hereditary spastic paraplegia' (SPG). The patients ranged in age from 10 to 27 years. All patients were noted to have mild cognitive delay with learning disability and reduced verbal fluency between 2 and 7 years of age. In family branch I, 3 sibs had slowly progressive lower limb spasticity starting in adolescence, but retained the ability to walk. These 3 patients also had febrile seizures. The youngest sib, examined at age 10, did not show spasticity, seizures, or any neurologic signs besides mild cognitive impairment. In family branch II, both affected sibs presented with juvenile-onset progressive spasticity, which progressed more quickly to tetraspasticity. These individuals also had additional abnormalities, including dystonia, progressive speech reduction, and dysphagia. One 33-year-old sib had a sensorimotor mixed axonal and demyelinating peripheral neuropathy. Brain imaging of 5 individuals showed T2-hyperintensities in the basal ganglia, consistent with Leigh-like syndrome, and urine analysis of 2 patients showed a 10-fold increase of 3-MGA. None of the patients had optic atrophy, deafness, or a history of liver failure; history from the neonatal period was not available. Whole-exome sequencing identified a homozygous intronic variant in the SERAC1 gene (<a href="/entry/614725#0007">614725.0007</a>). The mutation was confirmed by Sanger sequencing and segregated with the disorder in the family. Patient cells showed aberrant splicing and absence of the full-length SERAC1 protein, as well as impaired prostaglandin remodeling activity compared to wildtype. However, the prostaglandin imbalances were milder than those observed in patients with the classic infantile-onset disease, suggesting a basis for the milder phenotype in the Iraqi family. The findings expanded the phenotype resulting from SERAC1 mutations, showing a clinical spectrum of severity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28916646" 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="molecularGenetics" class="mim-anchor"></a>
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<p>In 15 individuals from 13 families with 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, <a href="#8" class="mim-tip-reference" title="Wortmann, S. B., Vaz, F. M., Gardeitchik, T., Vissers, L. E. L. M., Renkema, G. H., Schuurs-Hoeijmakers, J. H. M., Kulik, W., Lammens, M., Christin, C., Kluijtmans, L. A. J., Rodenburg, R. J., Nijtmans, L. G. J., and 22 others. &lt;strong&gt;Mutations in the phospholipid remodeling gene SERCA1 impair mitochondrial function and intracellular cholesterol trafficking and cause dystonia and deafness.&lt;/strong&gt; Nature Genet. 44: 797-802, 2012.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/22683713/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;22683713&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng.2325&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="22683713">Wortmann et al. (2012)</a> identified 14 different homozygous or compound heterozygous mutations in the SERAC1 gene (see, e.g., <a href="/entry/614725#0001">614725.0001</a>-<a href="/entry/614725#0005">614725.0005</a>). The first 2 mutations were identified by exome sequencing and confirmed by Sanger sequencing. Four of the patients had previously been reported by <a href="#9" class="mim-tip-reference" title="Wortmann, S., Rodenburg, R. J. T., Huizing, M., Loupatty, F. J., de Koning, T., Kluijtmans, L. A. J., Engelke, U., Wevers, R., Smeitink, J. A. M., Morava, E. &lt;strong&gt;Association of 3-methylglutaconic aciduria with sensori-neural deafness, encephalopathy, and Leigh-like syndrome (MEGDEL association) in four patients with a disorder of the oxidative phosphorylation.&lt;/strong&gt; Molec. Genet. Metab. 88: 47-52, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16527507/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16527507&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2006.01.013&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16527507">Wortmann et al. (2006)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=22683713+16527507" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a patient with MEGDEL, <a href="#6" class="mim-tip-reference" title="Tort, F., Garcia-Silva, M. T., Ferrer-Cortes, X., Navarro-Sastre, A., Garcia-Villoria, J., Coll, M. J., Vidal, E., Jimenez-Almazan, J., Dopazo, J., Briones, P., Elpeleg, O., Ribes, A. &lt;strong&gt;Exome sequencing identifies a new mutation in SERAC1 in a patient with 3-methylglutaconic aciduria.&lt;/strong&gt; Molec. Genet. Metab. 110: 73-77, 2013.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/23707711/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;23707711&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2013.04.021&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="23707711">Tort et al. (2013)</a> identified a homozygous truncating mutation in the SERAC1 gene (R68X; <a href="/entry/614725#0006">614725.0006</a>). The mutation was found by exome sequencing and segregated with the disorder in the family. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23707711" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Among 67 patients with MEGDEL, including 39 previously unreported individuals, <a href="#2" class="mim-tip-reference" title="Maas, R. R., Iwanicka-Pronicka, K., Kalkan Ucar, S., Alhaddad, B., AlSayed, M., Al-Owain, M. A., Al-Zaidan, H. I., Balasubramaniam, S., Baric, I., Bubshait, D. K., Burlina, A., Christodoulou, J., and 46 others. &lt;strong&gt;Progressive deafness-dystonia due to SERAC1 mutations: a study of 67 cases.&lt;/strong&gt; Ann. Neurol. 82: 1004-1015, 2017.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29205472/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;29205472&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=29205472[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.25110&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="29205472">Maas et al. (2017)</a> identified 41 SERAC1 sequence variants, including 20 novel variants. The mutations were located throughout the gene, with no hotspots, although there were several recurrent mutations, suggesting founder effects in certain populations. Most of the mutations were predicted to result in a loss of function, suggesting that missense mutations may be better tolerated. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29205472" 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 unrelated Indian patients, born to consanguineous parents, with MEGDEL, <a href="#3" class="mim-tip-reference" title="Radha Rama Devi, A. R., Lingappa, L. &lt;strong&gt;Novel mutations in SERAC1 gene in two Indian patients presenting with dystonia and intellectual disability.&lt;/strong&gt; Europ. J. Med. Genet. 61: 100-103, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/28778788/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;28778788&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ejmg.2017.07.013&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="28778788">Radha Rama Devi and Lingappa (2018)</a> identified homozygous mutations (<a href="/entry/614725#0008">614725.0008</a> and <a href="/entry/614725#0009">614725.0009</a>) in the SERAC2 gene. The mutations were found by whole-exome sequencing. In 1 family, the parents were confirmed by Sanger sequencing to be carriers; in the other family, the parents refused to be sequenced. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28778788" 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 Saudi Arabian boy with MEGDEL, <a href="#1" class="mim-tip-reference" title="Lumish, H. S., Yang, Y., Xia, F., Wilson, A., Chung, W. K. &lt;strong&gt;The expanding MEGDEL phenotype: optic nerve atrophy, microcephaly, and myoclonic epilepsy in a child with SERAC1 mutations.&lt;/strong&gt; JIMD Rep. 16: 75-79, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/24997715/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;24997715&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/8904_2014_322&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="24997715">Lumish et al. (2014)</a> identified compound heterozygous mutations in the SERAC2 gene (<a href="/entry/614725#0001">614725.0001</a> and <a href="/entry/614725#0010">614725.0010</a>). The mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing. The father carried one of the mutations; the mother's status was not given. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24997715" 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="#2" class="mim-tip-reference" title="Maas, R. R., Iwanicka-Pronicka, K., Kalkan Ucar, S., Alhaddad, B., AlSayed, M., Al-Owain, M. A., Al-Zaidan, H. I., Balasubramaniam, S., Baric, I., Bubshait, D. K., Burlina, A., Christodoulou, J., and 46 others. &lt;strong&gt;Progressive deafness-dystonia due to SERAC1 mutations: a study of 67 cases.&lt;/strong&gt; Ann. Neurol. 82: 1004-1015, 2017.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29205472/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;29205472&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=29205472[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.25110&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="29205472">Maas et al. (2017)</a> estimated that approximately 27 children with MEGDEL will be born each year worldwide. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29205472" 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>REFERENCES</strong>
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<a id="Lumish2014" class="mim-anchor"></a>
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Lumish, H. S., Yang, Y., Xia, F., Wilson, A., Chung, W. K.
<strong>The expanding MEGDEL phenotype: optic nerve atrophy, microcephaly, and myoclonic epilepsy in a child with SERAC1 mutations.</strong>
JIMD Rep. 16: 75-79, 2014.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24997715/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24997715</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24997715" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/8904_2014_322" target="_blank">Full Text</a>]
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<a id="Maas2017" class="mim-anchor"></a>
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Maas, R. R., Iwanicka-Pronicka, K., Kalkan Ucar, S., Alhaddad, B., AlSayed, M., Al-Owain, M. A., Al-Zaidan, H. I., Balasubramaniam, S., Baric, I., Bubshait, D. K., Burlina, A., Christodoulou, J., and 46 others.
<strong>Progressive deafness-dystonia due to SERAC1 mutations: a study of 67 cases.</strong>
Ann. Neurol. 82: 1004-1015, 2017.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29205472/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29205472</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29205472[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=29205472" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ana.25110" target="_blank">Full Text</a>]
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<a id="Radha Rama Devi2018" class="mim-anchor"></a>
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Radha Rama Devi, A. R., Lingappa, L.
<strong>Novel mutations in SERAC1 gene in two Indian patients presenting with dystonia and intellectual disability.</strong>
Europ. J. Med. Genet. 61: 100-103, 2018.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28778788/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28778788</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28778788" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.ejmg.2017.07.013" target="_blank">Full Text</a>]
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<a id="Roeben2018" class="mim-anchor"></a>
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Roeben, B., Schule, R., Ruf, S., Bender, B., Alhaddad, B., Benkert, T., Meitinger, T., Reich, S., Bohringer, J., Langhans, C.-D., Vaz, F. M., Wortmann, S. B., Marquart, T., Haack, T. B., Krageloh-Mann, I., Schols, L., Synofzik, M.
<strong>SERAC1 deficiency causes complicated HSP: evidence from a novel splice mutation in a large family.</strong>
J. Med. Genet. 55: 39-47, 2018.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28916646/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28916646</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28916646" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmedgenet-2017-104622" target="_blank">Full Text</a>]
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<a id="Sarig2013" class="mim-anchor"></a>
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Sarig, O., Goldsher, D., Nousbeck, J., Fuchs-Telem, D., Cohen-Katsenelson, K., Iancu, T. C., Manov, I., Saada, A., Sprecher, E., Mandel, H.
<strong>Infantile mitochondrial hepatopathy is a cardinal feature of MEGDEL syndrome (3-methylglutaconic aciduria type IV with sensorineural deafness, encephalopathy and Leigh-like syndrome) caused by novel mutations in SERAC1.</strong>
Am. J. Med. Genet. 161A: 2204-2215, 2013.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23918762/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23918762</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23918762" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.36059" target="_blank">Full Text</a>]
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<a id="Tort2013" class="mim-anchor"></a>
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Tort, F., Garcia-Silva, M. T., Ferrer-Cortes, X., Navarro-Sastre, A., Garcia-Villoria, J., Coll, M. J., Vidal, E., Jimenez-Almazan, J., Dopazo, J., Briones, P., Elpeleg, O., Ribes, A.
<strong>Exome sequencing identifies a new mutation in SERAC1 in a patient with 3-methylglutaconic aciduria.</strong>
Molec. Genet. Metab. 110: 73-77, 2013.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23707711/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23707711</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23707711" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.ymgme.2013.04.021" target="_blank">Full Text</a>]
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<a id="Wortmann2009" class="mim-anchor"></a>
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Wortmann, S. B., Rodenburg, R. J. T., Jonckheere, A., de Vries, M. C., Huizing, M., Heldt, K., van den Heuvel, L. P., Wendel, U., Kluijtmans, L. A., Engelke, U. F., Wevers, R. A., Smeitink, J. A. M., Morava, E.
<strong>Biochemical and genetic analysis of 3-methylglutaconic aciduria type IV: a diagnostic strategy.</strong>
Brain 132: 136-146, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19015156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19015156</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19015156" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/brain/awn296" target="_blank">Full Text</a>]
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<a id="Wortmann2012" class="mim-anchor"></a>
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Wortmann, S. B., Vaz, F. M., Gardeitchik, T., Vissers, L. E. L. M., Renkema, G. H., Schuurs-Hoeijmakers, J. H. M., Kulik, W., Lammens, M., Christin, C., Kluijtmans, L. A. J., Rodenburg, R. J., Nijtmans, L. G. J., and 22 others.
<strong>Mutations in the phospholipid remodeling gene SERCA1 impair mitochondrial function and intracellular cholesterol trafficking and cause dystonia and deafness.</strong>
Nature Genet. 44: 797-802, 2012.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22683713/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22683713</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22683713" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/ng.2325" target="_blank">Full Text</a>]
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<a id="Wortmann2006" class="mim-anchor"></a>
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Wortmann, S., Rodenburg, R. J. T., Huizing, M., Loupatty, F. J., de Koning, T., Kluijtmans, L. A. J., Engelke, U., Wevers, R., Smeitink, J. A. M., Morava, E.
<strong>Association of 3-methylglutaconic aciduria with sensori-neural deafness, encephalopathy, and Leigh-like syndrome (MEGDEL association) in four patients with a disorder of the oxidative phosphorylation.</strong>
Molec. Genet. Metab. 88: 47-52, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16527507/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16527507</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16527507" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.ymgme.2006.01.013" target="_blank">Full Text</a>]
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Hilary J. Vernon - updated : 02/29/2024
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Cassandra L. Kniffin - updated : 02/19/2018<br>Cassandra L. Kniffin - updated : 01/26/2018<br>Cassandra L. Kniffin - updated : 3/18/2014<br>Sonja A. Rasmussen - updated : 12/12/2013
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Cassandra L. Kniffin : 7/24/2012
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carol : 03/01/2024
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carol : 02/29/2024<br>carol : 02/22/2018<br>ckniffin : 02/19/2018<br>carol : 02/01/2018<br>carol : 01/31/2018<br>ckniffin : 01/26/2018<br>carol : 08/02/2017<br>carol : 10/24/2016<br>carol : 03/20/2015<br>ckniffin : 3/19/2015<br>carol : 3/18/2014<br>ckniffin : 3/18/2014<br>joanna : 12/27/2013<br>carol : 12/12/2013<br>terry : 7/31/2012<br>carol : 7/25/2012<br>ckniffin : 7/24/2012
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<strong>#</strong> 614739
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3-METHYLGLUTACONIC ACIDURIA WITH DEAFNESS, ENCEPHALOPATHY, AND LEIGH-LIKE SYNDROME; MEGDEL
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<em>Alternative titles; symbols</em>
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3-METHYLGLUTACONIC ACIDURIA WITH DYSTONIA-DEAFNESS, HEPATOPATHY, ENCEPHALOPATHY, AND LEIGH-LIKE SYNDROME; MEGDHEL<br />
3-METHYLGLUTACONIC ACIDURIA, TYPE VI; MGCA6
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<strong>SNOMEDCT:</strong> 711409002; &nbsp;
<strong>ORPHA:</strong> 352328; &nbsp;
<strong>DO:</strong> 0110001; &nbsp;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Inheritance
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6q25.3
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3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome
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614739
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Autosomal recessive
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3
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SERAC1
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614725
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<p>A number sign (#) is used with this entry because 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome (MEGDEL), also referred to as 3-methylglutaconic aciduria type VI (MGCA6), is caused by homozygous or compound heterozygous mutation in the SERAC1 gene (614725) on chromosome 6q25.</p>
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<strong>Description</strong>
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<p>MEGDEL is an autosomal recessive disorder characterized by childhood onset of delayed psychomotor development or psychomotor regression, sensorineural deafness, spasticity or dystonia, and increased excretion of 3-methylglutaconic acid. Brain imaging shows cerebral and cerebellar atrophy as well as lesions in the basal ganglia reminiscent of Leigh syndrome (256000). Laboratory studies show increased serum lactate and alanine, mitochondrial oxidative phosphorylation defects, abnormal mitochondria, abnormal phosphatidylglycerol and cardiolipin profiles in fibroblasts, and abnormal accumulation of unesterified cholesterol within cells (summary by Wortmann et al., 2012). About 50% of patients develop severe, but transient, liver dysfunction and/or signs of liver failure, in the neonatal period or during the first year of life, prompting some authors to suggest the name 'MEGDHEL' syndrome, with the 'H' referring to 'hepatopathy' (summary by Maas et al., 2017). Some patients may have a milder presentation with juvenile-onset spasticity and mild cognitive impairment, indicating a broader phenotypic spectrum (Roeben et al., 2018). </p><p>For a general phenotypic description and a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA type I (250950).</p>
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<strong>Clinical Features</strong>
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<p>Wortmann et al. (2006, 2009) reported 4 unrelated girls with an encephalomyopathy associated with mildly and intermittently increased urinary 3-methylglutaconic aciduria. Three children were born of 3 unrelated sets of consanguineous Turkish parents, and the fourth child was born of unrelated Dutch parents. All presented in the neonatal period with severe infections and had episodes of lactic acidosis and hypoglycemia. Other features included failure to thrive, loss of motor skills, mental retardation, sensorineural deafness, and hypotonia with progressive spasticity. One patient had delayed development, 1 did not develop at all, and the other 2 showed developmental regression during early childhood. Brain MRI showed cerebral and cerebellar atrophy as well as bilateral hyperintensities in the basal ganglia reminiscent of Leigh syndrome. Mitochondrial complex I deficiency was found in muscle and fibroblasts. Two patients died at age 3 and 16 years, respectively. Genetic analysis did not find mutations in several candidate genes. </p><p>Wortmann et al. (2012) reported 11 additional patients with MEGDEL, including 2 relatives of 1 of the Turkish patients reported by Wortmann et al. (2006). The phenotype was relatively homogeneous, with psychomotor retardation, spasticity or dystonia, sensorineural deafness, Leigh syndrome-like lesions on brain imaging, and brain atrophy. Laboratory studies showed 3-methylglutaconic aciduria, increased serum lactate, and defects in oxidative phosphorylation. Patient fibroblasts showed an increased phosphatidylglycerol 34:1 to phosphatidylglycerol 36:1 ratio as well as abnormal cardiolipin subspecies. There was abnormal intracellular accumulation of unesterified cholesterol, and some patients had low serum cholesterol. </p><p>Sarig et al. (2013) reported 4 males, 2 each from 2 unrelated, highly consanguineous families, with features consistent with MEGDEL syndrome, including 3-methylglutaconic aciduria, sensorineural deafness, encephalopathy, and brain magnetic resonance imaging with findings consistent with Leigh-like syndrome. All 4 patients presented at age 24 to 48 hours with hypotonia and evidence of liver dysfunction, including symptomatic hypoglycemia, lactic acidosis, elevated serum transaminase levels, coagulopathy, hyperammonemia, and markedly elevated serum alpha-fetoprotein. During periods of acute infection in the first year of life, the patients experienced a few episodes of liver dysfunction, but these episodes did not recur later in life. Electron microscopy of a liver biopsy from 1 patient showed hepatocyte steatosis with mitochondrial ultrastructural changes, consistent with a mitochondrial oxidative phosphorylation disorder and abnormal lipid metabolism. The patients subsequently developed features of MEGDEL syndrome. The families were found to have 2 homozygous mutations in the SERAC1 gene that led to decreased or absent gene expression. Sarig et al. (2013) suggested that neonatal liver disease is a component of the phenotypic spectrum of MEGDEL syndrome and proposed that the disease be renamed MEGDHEL syndrome. </p><p>Tort et al. (2013) reported a girl, born of unrelated parents, with MEGDEL. She presented on the fourth day of life with respiratory distress, refusal to feed, and jaundice, and was found to have metabolic acidosis with ketonuria, hyperammonemia, and elevated liver enzymes. During the first few years of life, she developed oral dyskinesia, hypotonia, truncal ataxia, episodic ketotic hypoglycemia, and psychomotor deterioration. Brain imaging showed features typical of Leigh syndrome. Urinary analysis showed 3-methylglutaconic and 3-methylglutaric aciduria. Sensorineural deafness and optic atrophy became apparent in her teenage years. At age 19 years, she was severely affected, with microcephaly, poor communication skills, inability to hold up her head, and multiple joint problems. </p><p>Maas et al. (2017) reviewed the clinical features of 67 patients with MEGDEL, including 39 previously unreported individuals. Most (64%) of the families were consanguineous. Most of the individuals were of European ancestry, although several dozen patients were from Africa, Asia, the Middle East, or Australia, indicating that MEGDEL is a panethnic disorder. With the exception of 2 families with a milder phenotype and onset later in childhood, all affected individuals showed a strikingly homogeneous phenotype and time course. Sixteen patients died at a median age of 9 years, mostly due to respiratory infections. In the neonatal period, 48% of patients showed liver dysfunction and hypoglycemia, with variable abnormal liver enzymes, increased bilirubin, and disturbed coagulation in the more severe cases. Signs of hepatic dysfunction during the first year of life were common in this group, but resolved afterwards. Other presenting symptoms of the disorder included neonatal sepsis, hypotonia, and delayed motor development. The majority of patients lost previously acquired skills in the first year of life. Patients had early-onset progressive spasticity, dystonia, and oropharyngeal dyskinesia, and most (78%) never learned to walk. All had intellectual disability that varied from mild (12%) to severe (73%), and nearly all (93%) were completely dependent for activities of daily living. Additional features included epilepsy (35%), sensorineural hearing impairment (79%), absent speech (58%), impaired vision (42%), retinal pigmentary changes (6%), optic atrophy (25%), recurrent respiratory infections (42%), scoliosis (39%), and poor feeding (79%), often necessitating tube feeding. Less common features included transient renal tubular dysfunction (12%) and cardiac abnormalities (7%). Laboratory studies showed increased urinary 3-MGA and increased serum lactate, and brain imaging showed lesions in the basal ganglia, consistent with Leigh syndrome. Maas et al. (2017) concluded that MEGDEL is best classified as a disorder of the biosynthesis of complex lipids with secondary mitochondrial dysfunction, although MEGDEL syndrome displays typical findings and the progressive course of a mitochondrial disorder. However, mitochondrial dysfunction in tissue varies greatly and may be unremarkable. </p><p>Radha Rama Devi and Lingappa (2018) reported 2 unrelated Indian patients with MEGDEL. The first patient presented in the neonatal period with respiratory distress, neonatal hepatitis, elevated serum lactate, and metabolic acidosis. At 15 months of age, she had developmental delay and dystonia. At age 7 years she had generalized dystonia, seizures, spasticity, and flexion contractures. Brain MRI showed bilateral abnormal signal in the putamen and caudate. The second patient had normal development until 3 years of age, but then had progressive developmental regression. At age 4 years she had hepatitis, jaundice, and elevated serum lactate. At age 11 years, she had ataxia, severe dystonia, and dysarthria. Brain MRI at age 11 years showed bilateral abnormal signal in the putamen and claustrum. </p><p>Lumish et al. (2014) reported a 5-year-old boy with developmental delay, developmental regression, bilateral optic nerve atrophy, microcephaly, sensorineural hearing loss, and myoclonic epilepsy. After birth, he had respiratory distress, an anion gap metabolic acidosis, and mild elevations in liver function tests. His developmental milestones were delayed. He experienced developmental regression at 3 years of age. An EEG at age 22 months was suggestive of partial epilepsy. MRI of the brain at age 22 months showed a Leigh syndrome-like pattern. Follow-up MRIs demonstrated progressive basal ganglia and cerebellar volume loss. </p><p><strong><em>Clinical Variability</em></strong></p><p>
Roeben et al. (2018) reported a large consanguineous Iraqi kindred in which 6 individuals from 2 different family branches had a relatively mild form of MEGDEL, which was characterized by the authors as 'juvenile-onset complicated hereditary spastic paraplegia' (SPG). The patients ranged in age from 10 to 27 years. All patients were noted to have mild cognitive delay with learning disability and reduced verbal fluency between 2 and 7 years of age. In family branch I, 3 sibs had slowly progressive lower limb spasticity starting in adolescence, but retained the ability to walk. These 3 patients also had febrile seizures. The youngest sib, examined at age 10, did not show spasticity, seizures, or any neurologic signs besides mild cognitive impairment. In family branch II, both affected sibs presented with juvenile-onset progressive spasticity, which progressed more quickly to tetraspasticity. These individuals also had additional abnormalities, including dystonia, progressive speech reduction, and dysphagia. One 33-year-old sib had a sensorimotor mixed axonal and demyelinating peripheral neuropathy. Brain imaging of 5 individuals showed T2-hyperintensities in the basal ganglia, consistent with Leigh-like syndrome, and urine analysis of 2 patients showed a 10-fold increase of 3-MGA. None of the patients had optic atrophy, deafness, or a history of liver failure; history from the neonatal period was not available. Whole-exome sequencing identified a homozygous intronic variant in the SERAC1 gene (614725.0007). The mutation was confirmed by Sanger sequencing and segregated with the disorder in the family. Patient cells showed aberrant splicing and absence of the full-length SERAC1 protein, as well as impaired prostaglandin remodeling activity compared to wildtype. However, the prostaglandin imbalances were milder than those observed in patients with the classic infantile-onset disease, suggesting a basis for the milder phenotype in the Iraqi family. The findings expanded the phenotype resulting from SERAC1 mutations, showing a clinical spectrum of severity. </p>
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<strong>Molecular Genetics</strong>
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<p>In 15 individuals from 13 families with 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, Wortmann et al. (2012) identified 14 different homozygous or compound heterozygous mutations in the SERAC1 gene (see, e.g., 614725.0001-614725.0005). The first 2 mutations were identified by exome sequencing and confirmed by Sanger sequencing. Four of the patients had previously been reported by Wortmann et al. (2006). </p><p>In a patient with MEGDEL, Tort et al. (2013) identified a homozygous truncating mutation in the SERAC1 gene (R68X; 614725.0006). The mutation was found by exome sequencing and segregated with the disorder in the family. </p><p>Among 67 patients with MEGDEL, including 39 previously unreported individuals, Maas et al. (2017) identified 41 SERAC1 sequence variants, including 20 novel variants. The mutations were located throughout the gene, with no hotspots, although there were several recurrent mutations, suggesting founder effects in certain populations. Most of the mutations were predicted to result in a loss of function, suggesting that missense mutations may be better tolerated. </p><p>In 2 unrelated Indian patients, born to consanguineous parents, with MEGDEL, Radha Rama Devi and Lingappa (2018) identified homozygous mutations (614725.0008 and 614725.0009) in the SERAC2 gene. The mutations were found by whole-exome sequencing. In 1 family, the parents were confirmed by Sanger sequencing to be carriers; in the other family, the parents refused to be sequenced. </p><p>In a Saudi Arabian boy with MEGDEL, Lumish et al. (2014) identified compound heterozygous mutations in the SERAC2 gene (614725.0001 and 614725.0010). The mutations were identified by whole-exome sequencing and confirmed by Sanger sequencing. The father carried one of the mutations; the mother's status was not given. </p>
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<strong>Population Genetics</strong>
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<p>Maas et al. (2017) estimated that approximately 27 children with MEGDEL will be born each year worldwide. </p>
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<strong>REFERENCES</strong>
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<li>
<p class="mim-text-font">
Lumish, H. S., Yang, Y., Xia, F., Wilson, A., Chung, W. K.
<strong>The expanding MEGDEL phenotype: optic nerve atrophy, microcephaly, and myoclonic epilepsy in a child with SERAC1 mutations.</strong>
JIMD Rep. 16: 75-79, 2014.
[PubMed: 24997715]
[Full Text: https://doi.org/10.1007/8904_2014_322]
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<li>
<p class="mim-text-font">
Maas, R. R., Iwanicka-Pronicka, K., Kalkan Ucar, S., Alhaddad, B., AlSayed, M., Al-Owain, M. A., Al-Zaidan, H. I., Balasubramaniam, S., Baric, I., Bubshait, D. K., Burlina, A., Christodoulou, J., and 46 others.
<strong>Progressive deafness-dystonia due to SERAC1 mutations: a study of 67 cases.</strong>
Ann. Neurol. 82: 1004-1015, 2017.
[PubMed: 29205472]
[Full Text: https://doi.org/10.1002/ana.25110]
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<li>
<p class="mim-text-font">
Radha Rama Devi, A. R., Lingappa, L.
<strong>Novel mutations in SERAC1 gene in two Indian patients presenting with dystonia and intellectual disability.</strong>
Europ. J. Med. Genet. 61: 100-103, 2018.
[PubMed: 28778788]
[Full Text: https://doi.org/10.1016/j.ejmg.2017.07.013]
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<li>
<p class="mim-text-font">
Roeben, B., Schule, R., Ruf, S., Bender, B., Alhaddad, B., Benkert, T., Meitinger, T., Reich, S., Bohringer, J., Langhans, C.-D., Vaz, F. M., Wortmann, S. B., Marquart, T., Haack, T. B., Krageloh-Mann, I., Schols, L., Synofzik, M.
<strong>SERAC1 deficiency causes complicated HSP: evidence from a novel splice mutation in a large family.</strong>
J. Med. Genet. 55: 39-47, 2018.
[PubMed: 28916646]
[Full Text: https://doi.org/10.1136/jmedgenet-2017-104622]
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<li>
<p class="mim-text-font">
Sarig, O., Goldsher, D., Nousbeck, J., Fuchs-Telem, D., Cohen-Katsenelson, K., Iancu, T. C., Manov, I., Saada, A., Sprecher, E., Mandel, H.
<strong>Infantile mitochondrial hepatopathy is a cardinal feature of MEGDEL syndrome (3-methylglutaconic aciduria type IV with sensorineural deafness, encephalopathy and Leigh-like syndrome) caused by novel mutations in SERAC1.</strong>
Am. J. Med. Genet. 161A: 2204-2215, 2013.
[PubMed: 23918762]
[Full Text: https://doi.org/10.1002/ajmg.a.36059]
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<li>
<p class="mim-text-font">
Tort, F., Garcia-Silva, M. T., Ferrer-Cortes, X., Navarro-Sastre, A., Garcia-Villoria, J., Coll, M. J., Vidal, E., Jimenez-Almazan, J., Dopazo, J., Briones, P., Elpeleg, O., Ribes, A.
<strong>Exome sequencing identifies a new mutation in SERAC1 in a patient with 3-methylglutaconic aciduria.</strong>
Molec. Genet. Metab. 110: 73-77, 2013.
[PubMed: 23707711]
[Full Text: https://doi.org/10.1016/j.ymgme.2013.04.021]
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<li>
<p class="mim-text-font">
Wortmann, S. B., Rodenburg, R. J. T., Jonckheere, A., de Vries, M. C., Huizing, M., Heldt, K., van den Heuvel, L. P., Wendel, U., Kluijtmans, L. A., Engelke, U. F., Wevers, R. A., Smeitink, J. A. M., Morava, E.
<strong>Biochemical and genetic analysis of 3-methylglutaconic aciduria type IV: a diagnostic strategy.</strong>
Brain 132: 136-146, 2009.
[PubMed: 19015156]
[Full Text: https://doi.org/10.1093/brain/awn296]
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<li>
<p class="mim-text-font">
Wortmann, S. B., Vaz, F. M., Gardeitchik, T., Vissers, L. E. L. M., Renkema, G. H., Schuurs-Hoeijmakers, J. H. M., Kulik, W., Lammens, M., Christin, C., Kluijtmans, L. A. J., Rodenburg, R. J., Nijtmans, L. G. J., and 22 others.
<strong>Mutations in the phospholipid remodeling gene SERCA1 impair mitochondrial function and intracellular cholesterol trafficking and cause dystonia and deafness.</strong>
Nature Genet. 44: 797-802, 2012.
[PubMed: 22683713]
[Full Text: https://doi.org/10.1038/ng.2325]
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<li>
<p class="mim-text-font">
Wortmann, S., Rodenburg, R. J. T., Huizing, M., Loupatty, F. J., de Koning, T., Kluijtmans, L. A. J., Engelke, U., Wevers, R., Smeitink, J. A. M., Morava, E.
<strong>Association of 3-methylglutaconic aciduria with sensori-neural deafness, encephalopathy, and Leigh-like syndrome (MEGDEL association) in four patients with a disorder of the oxidative phosphorylation.</strong>
Molec. Genet. Metab. 88: 47-52, 2006.
[PubMed: 16527507]
[Full Text: https://doi.org/10.1016/j.ymgme.2006.01.013]
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Hilary J. Vernon - updated : 02/29/2024<br>Cassandra L. Kniffin - updated : 02/19/2018<br>Cassandra L. Kniffin - updated : 01/26/2018<br>Cassandra L. Kniffin - updated : 3/18/2014<br>Sonja A. Rasmussen - updated : 12/12/2013
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