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<title>
Entry
- #246900 - DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY; DLDD
- OMIM
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<span class="h4">#246900</span>
<br />
<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/246900"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS248600"> <strong>Phenotypic Series</strong> </a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#populationGenetics">Population Genetics</a>
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<div><a href="https://clinicaltrials.gov/search?cond=DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
<div><a href="#mimEuroGentestFold" id="mimEuroGentestToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A list of European laboratories that offer genetic testing."><span id="mimEuroGentestToggleTriangle" class="small" style="margin-left: -0.8em;">&#9658;</span>EuroGentest</div>
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=5520&Typ=Pat" title="Pyruvate dehydrogenase E3 deficiency" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Pyruvate dehydrogenase E3 …&nbsp;</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=467&Typ=Pat" title="Pyruvate dehydrogenase deficiency" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Pyruvate dehydrogenase def…&nbsp;</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK220444/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
<div><a href="https://medlineplus.gov/genetics/condition/dihydrolipoamide-dehydrogenase-deficiency" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div style="margin-left: 0.5em;"><a href="https://www.acmg.net/PDFLibrary/Leucine.pdf" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Newborn Screening', 'domain': 'www.acmg.net'})">ACMG ACT Sheet</a></div><div style="margin-left: 0.5em;"><a href="https://www.acmg.net/PDFLibrary/Leucine-Algorithm.pdf" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Newborn Screening', 'domain': 'www.acmg.net'})">ACMG Algorithm</a></div>
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<div><a href="#mimOrphanetFold" id="mimOrphanetToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="European reference portal for information on rare diseases and orphan drugs."><span id="mimOrphanetToggleTriangle" class="small" style="margin-left: -0.8em;">&#9658;</span>Orphanet</div>
<div id="mimOrphanetFold" class="collapse">
<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2394" title="Pyruvate dehydrogenase E3 deficiency" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Pyruvate dehydrogenase E3 …</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=765" title="Pyruvate dehydrogenase deficiency" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Pyruvate dehydrogenase def…</a></div>
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</div>
</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
<span class="panel-title">
<span class="small">
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Animal Models</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.alliancegenome.org/disease/DOID:9269" 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/246900" 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://wormbase.org/resources/disease/DOID:9269" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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</div>
</div>
</div>
</div>
</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;
</span>
</span>
</div>
<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> 29914000<br />
<strong>ORPHA:</strong> 2394, 765<br />
<strong>DO:</strong> 9269<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>
246900
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY; DLDD
</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">
DLD DEFICIENCY<br />
E3 DEFICIENCY<br />
LIPOAMIDE DEHYDROGENASE DEFICIENCY, LACTIC ACIDOSIS DUE TO<br />
MAPLE SYRUP URINE DISEASE, TYPE III; MSUD3
</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/7/583?start=-3&limit=10&highlight=583">
7q31.1
</a>
</span>
</td>
<td>
<span class="mim-font">
Dihydrolipoamide dehydrogenase deficiency
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/246900"> 246900 </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">
DLD
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/238331"> 238331 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/246900" class="btn btn-warning" role="button"> Clinical Synopsis </a>
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
<span class="caret"></span>
<span class="sr-only">Toggle Dropdown</span>
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</div>
&nbsp;
<div class="btn-group">
<a href="/phenotypicSeries/PS248600" 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/246900" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/246900" 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> 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 <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>
<div>
<div>
<span class="h5 mim-font">
<strong> CARDIOVASCULAR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Heart </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hypertrophic cardiomyopathy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/195020003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">195020003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/233873004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">233873004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/45227007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">45227007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I42.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/I42.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/425.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">425.1</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/425.11" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">425.11</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551472&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551472</a>, <a href="https://bioportal.bioontology.org/search?q=C0340425&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0340425</a>, <a href="https://bioportal.bioontology.org/search?q=C0007194&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007194</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001639</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001639</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ABDOMEN </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Liver </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hepatomegaly (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80515008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80515008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019209&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019209</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span><br /> -
Liver dysfunction (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/75183008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">75183008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0086565&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0086565</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001410" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001410</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0002910" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002910</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001410" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001410</a>]</span><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">
- Vomiting, recurrent, severe <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3550495&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3550495</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422400008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422400008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/300359004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">300359004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249497008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249497008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R11.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R11.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R11.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R11.10</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002013" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002013</a>]</span><br /> -
Poor feeding <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/299698007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">299698007</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">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0576456&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0576456</a>, <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> 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> 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">
- Encephalopathy, episodic <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3280888&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3280888</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/81308009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">81308009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G93.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G93.40</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/348.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">348.30</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/348.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">348.3</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001298" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001298</a>]</span><br /> -
Delayed psychomotor development (in most patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/224958001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">224958001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F88</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0557874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0557874</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span><br /> -
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 /> -
Lethargy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/214264003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">214264003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R53.83" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R53.83</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0023380&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023380</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001254" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001254</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001254" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001254</a>]</span><br /> -
Ataxia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/20262006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">20262006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/39384006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">39384006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/85102008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">85102008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R27.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R27.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.84" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.84</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0004134&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0004134</a>, <a href="https://bioportal.bioontology.org/search?q=C1135207&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1135207</a>, <a href="https://bioportal.bioontology.org/search?q=C0007758&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007758</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0010867" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010867</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>]</span><br /> -
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 /> -
Seizures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91175000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91175000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span><br /> -
Leigh syndrome (in some patients) <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 />
</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">
- Metabolic acidosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/59455009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">59455009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E87.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E87.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0220981&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0220981</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001942" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001942</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001942" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001942</a>]</span><br /> -
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 /> -
Episodic decompensation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3550504&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3550504</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">
- 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 /> -
Elevated pyruvate (in most patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3550496&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3550496</a>]</span><br /> -
Elevated branched-chain amino acids (in most patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3550497&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3550497</a>]</span><br /> -
Elevated alpha-ketoglutarate (in most patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3550498&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3550498</a>]</span><br /> -
Decreased activities of the pyruvate dehydrogenase complex, the alpha-ketoglutarate dehydrogenase complex, and the branched-chain alpha-keto acid dehydrogenase complex <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3550499&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3550499</a>]</span><br /> -
Abnormal liver enzymes (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/166643006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">166643006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0438237&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0438237</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002910" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002910</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002910" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002910</a>]</span><br />
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<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
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- Onset usually in the neonatal period although later onset has been reported<br /> -
Some patients may have normal psychomotor development<br /> -
Highly variable severity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1866862&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1866862</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 /> -
High mortality in infancy and early childhood (in some patients)<br />
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<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
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<div>
<span class="mim-font">
- Caused by mutation in the dihydrolipoamide dehydrogenase gene (DLD, <a href="/entry/238331#0001">238331.0001</a>)<br />
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<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<h5>
Maple syrup urine disease
- <a href="/phenotypicSeries/PS248600">PS248600</a>
- 5 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">
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<strong>Location</strong>
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<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
<strong>Phenotype</strong>
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<strong>Inheritance</strong>
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<strong>Phenotype<br />mapping key</strong>
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<strong>Phenotype<br />MIM number</strong>
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<strong>Gene/Locus</strong>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus<br />MIM number</strong>
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</thead>
<tbody>
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<td>
<span class="mim-font">
<a href="/geneMap/1/836?start=-3&limit=10&highlight=836"> 1p21.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620699"> Maple syrup urine disease, type II </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>
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<td>
<span class="mim-font">
<a href="/entry/620699"> 620699 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/248610"> DBT </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/248610"> 248610 </a>
</span>
</td>
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<td>
<span class="mim-font">
<a href="/geneMap/4/400?start=-3&limit=10&highlight=400"> 4q22.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615135"> Maple syrup urine disease, mild variant </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/615135"> 615135 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/611065"> PPM1K </a>
</span>
</td>
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<span class="mim-font">
<a href="/entry/611065"> 611065 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/669?start=-3&limit=10&highlight=669"> 6q14.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620698"> Maple syrup urine disease, type Ib </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/620698"> 620698 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/248611"> BCKDHB </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/248611"> 248611 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/7/583?start=-3&limit=10&highlight=583"> 7q31.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/246900"> Dihydrolipoamide dehydrogenase deficiency </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/246900"> 246900 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/238331"> DLD </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/238331"> 238331 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/730?start=-3&limit=10&highlight=730"> 19q13.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/248600"> Maple syrup urine disease, type Ia </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/248600"> 248600 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608348"> BCKDHA </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608348"> 608348 </a>
</span>
</td>
</tr>
</tbody>
</table>
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because dihydrolipoamide dehydrogenase deficiency (DLDD) is caused by homozygous or compound heterozygous mutation in the DLD gene (<a href="/entry/238331">238331</a>) on chromosome 7q31.</p>
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<a id="description" class="mim-anchor"></a>
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<strong>Description</strong>
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<p>Dihydrolipoamide dehydrogenase deficiency (DLDD) is an autosomal recessive metabolic disorder characterized biochemically by a combined deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), pyruvate dehydrogenase complex (PDC), and alpha-ketoglutarate dehydrogenase complex (KGDC). This is the result of E3 being a common component of all 3 mitochondrial multienzyme complexes. Clinically, affected individuals have lactic acidosis and neurologic deterioration due to sensitivity of the central nervous system to defects in oxidative metabolism. E3 deficiency is often associated with increased urinary excretion of alpha-keto acids, such as pyruvate (summary by <a href="#5" class="mim-tip-reference" title="Hong, Y. S., Kerr, D. S., Craigen, W. J., Tan, J., Pan, Y., Lusk, M., Patel, M. S. &lt;strong&gt;Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency.&lt;/strong&gt; Hum. Molec. Genet. 5: 1925-1930, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8968745/&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;8968745&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/5.12.1925&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="8968745">Hong et al., 1996</a>). E3 deficiency can also be associated with increased concentrations of branched-chain amino acids, as observed in maple syrup urine disease (MSUD; <a href="/entry/248600">248600</a>), and is sometimes referred to as 'MSUD type III,' although patients with E3 deficiency have additional biochemical defects (<a href="#3" class="mim-tip-reference" title="Chuang, D. T., Shih, V. E. &lt;strong&gt;Maple syrup urine disease (branched-chain ketoaciduria). In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. II. (8th ed.)&lt;/strong&gt; New York: McGraw-Hill (pub.) 2001. Pp. 1971-2005."None>Chuang and Shih, 2001</a>; <a href="#14" class="mim-tip-reference" title="Robinson, B. H. &lt;strong&gt;Lactic acidemia: disorders of pyruvate carboxylase and pyruvate dehydrogenase. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. II. (8th ed.)&lt;/strong&gt; New York: McGraw-Hill (pub.) 2001. Pp. 2275-2295."None>Robinson, 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8968745" 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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<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Clinical Features</strong>
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</h4>
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<p><a href="#13" class="mim-tip-reference" title="Robinson, B. H., Taylor, J., Sherwood, W. G. &lt;strong&gt;Deficiency of dihydrolipoyl dehydrogenase (a component of the pyruvate and alpha-ketoglutarate dehydrogenase complexes): a cause of congenital lactic acidosis in infancy.&lt;/strong&gt; Pediat. Res. 11: 1198-1202, 1977.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/413089/&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;413089&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1203/00006450-197712000-00006&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="413089">Robinson et al. (1977)</a> reported a male child, born of Caucasian first-cousin parents, who died at age 7 months with progressive neurologic deterioration and persistent metabolic acidosis. He was well until age 8 weeks, when he abruptly became ill with irregular labored respiration, increased muscle tone, bilateral optic atrophy, and metabolic acidosis. He had elevated blood pyruvate, lactate, alpha-ketoglutarate, and branched-chain amino acids, as well as occasional hypoglycemia. Thiamine therapy was of no benefit. Postmortem tissue analysis showed deficiency of the pyruvate dehydrogenase complex, and specifically of dihydrolipoyl dehydrogenase, or E3. <a href="#12" class="mim-tip-reference" title="Robinson, B. H., Taylor, J., Kahler, S. G., Kirkman, H. N. &lt;strong&gt;Lactic acidemia, neurologic deterioration and carbohydrate dependence in a girl with dihydrolipoyl dehydrogenase deficiency.&lt;/strong&gt; Europ. J. Pediat. 136: 35-39, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6894281/&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;6894281&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00441708&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="6894281">Robinson et al. (1981)</a> reported another similar case. The parents were normal in both cases, but the parents of 1 patient had decreased enzyme activity at about 30 to 42% of normal, supporting recessive inheritance. A primary deficiency of this enzyme had been suggested as the basic defect in Friedreich ataxia (<a href="/entry/229300">229300</a>), but <a href="#11" class="mim-tip-reference" title="Robinson, B. H., Sherwood, W. G., Kahler, S., O&#x27;Flynn, M. E., Nadler, H. &lt;strong&gt;Lipoamide dehydrogenase deficiency. (Letter)&lt;/strong&gt; New Eng. J. Med. 304: 53-54, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6893619/&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;6893619&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM198101013040116&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="6893619">Robinson et al. (1981)</a> concluded that the deficiency in Friedreich ataxia is likely a secondary phenomenon. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=413089+6893619+6894281" 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 case of E3 deficiency, <a href="#8" class="mim-tip-reference" title="Matalon, R., Michals, K., Stumpf, D., Goodman, S., Parks, J. &lt;strong&gt;Lactic acidosis due to lipoamide dehydrogenase (LAD) deficiency: improvement after oral lipoic acid. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 33: 48A, 1981."None>Matalon et al. (1981)</a> found that oral administration of lipoic acid resulted in almost complete clearance of abnormal organic aciduria and lactic and pyruvic acidemia, with clinical improvement. The patient had neonatal hypothermia, failure to thrive, and metabolic acidosis. In cultured fibroblasts, the E3 component was 23% of the control mean. <a href="#9" class="mim-tip-reference" title="Munnich, A., Saudubray, J. M., Taylor, J., Charpentier, C., Marsac, C., Rocchiccioli, F., Amedee-Manesme, O., Coude, F. X., Frezal, J., Robinson, B. H. &lt;strong&gt;Congenital lactic acidosis, alpha-ketoglutaric aciduria and variant form of maple syrup urine disease due to a single enzyme defect: dihydrolipoyl dehydrogenase deficiency.&lt;/strong&gt; Acta Paediat. Scand. 71: 167-171, 1982.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6897145/&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;6897145&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1651-2227.1982.tb09393.x&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="6897145">Munnich et al. (1982)</a> reported a 6-month-old girl with vomiting, hypotonia, and motor retardation who had combined chemical features of lactic acidosis, maple syrup urine disease, and ketoglutaric aciduria. E3 activity was reduced. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6897145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Sakaguchi, Y., Yoshino, M., Aramaki, S., Yoshida, I., Yamashita, F., Kuhara, T., Matsumoto, I., Hayashi, T. &lt;strong&gt;Dihydrolipoyl dehydrogenase deficiency: a therapeutic trial with branched-chain amino acid restriction.&lt;/strong&gt; Europ. J. Pediat. 145: 271-274, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3769994/&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;3769994&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00439399&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="3769994">Sakaguchi et al. (1986)</a> reported a patient with E3-deficient MSUD. In the first week of life, the patient's blood leucine was found to be 5 mg/dl, but the patient was left on a normal diet. At the age of 6 months, he exhibited hypotonia and minimal dystonic movements of the upper limbs. He had elevated plasma levels of pyruvate, alpha-ketoglutarate, and branched-chain amino acids and alpha-keto acids. Urinary excretion of these keto acids and their metabolites were also elevated. At 7 months of age, the patient was placed on a diet restricted in branched-chain amino acids, resulting in improvement of some biochemical and developmental parameters. The patient died at the age of 21 months, following a ketoacidotic episode. The total pyruvate dehydrogenase complex activity of the patient's cells was 10 to 30% that of control cells. Pyruvate dehydrogenase (E1) and dihydrolipoamide acetyltransferase (E2) activities were normal in the patient's muscle, but E3 activity was not detectable in either muscle or liver specimens obtained at autopsy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3769994" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 males born to first-cousin Algerian parents and presenting with hypotonia, metabolic acidosis, and hyperlactatemia immediately after birth, <a href="#1" class="mim-tip-reference" title="Bonnefont, J.-P., Chretien, D., Rustin, P., Robinson, B., Vassault, A., Aupetit, J., Charpentier, C., Rabier, D., Saudubray, J.-M., Munnich, A. &lt;strong&gt;Alpha-ketoglutarate dehydrogenase deficiency presenting as congenital lactic acidosis.&lt;/strong&gt; J. Pediat. 121: 255-258, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1640293/&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;1640293&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(05)81199-0&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="1640293">Bonnefont et al. (1992)</a> described a 'new' inborn error of the tricarboxylic acid cycle, alpha-ketoglutarate dehydrogenase. Neurologic deterioration resulted in death at about 30 months of age. In a review of the patients reported by <a href="#1" class="mim-tip-reference" title="Bonnefont, J.-P., Chretien, D., Rustin, P., Robinson, B., Vassault, A., Aupetit, J., Charpentier, C., Rabier, D., Saudubray, J.-M., Munnich, A. &lt;strong&gt;Alpha-ketoglutarate dehydrogenase deficiency presenting as congenital lactic acidosis.&lt;/strong&gt; J. Pediat. 121: 255-258, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1640293/&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;1640293&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(05)81199-0&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="1640293">Bonnefont et al. (1992)</a>, <a href="#10" class="mim-tip-reference" title="Odievre, M. H., Chretien, D., Munnich, A., Robinson, B. H., Dumoulin, R., Masmoudi, S., Kadhom, N., Rotig, A., Rustin, P., Bonnefont, J. P. &lt;strong&gt;A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency.&lt;/strong&gt; Hum. Mutat. 25: 323-324, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15712224/&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;15712224&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.9319&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="15712224">Odievre et al. (2005)</a> noted that 1 of the patients had hypertrophic cardiomyopathy. The patients showed lack of accumulation of branched-chain amino acids or pyruvate, but KGDC activity was markedly deficient. In fibroblasts derived from these patients, <a href="#10" class="mim-tip-reference" title="Odievre, M. H., Chretien, D., Munnich, A., Robinson, B. H., Dumoulin, R., Masmoudi, S., Kadhom, N., Rotig, A., Rustin, P., Bonnefont, J. P. &lt;strong&gt;A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency.&lt;/strong&gt; Hum. Mutat. 25: 323-324, 2005.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15712224/&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;15712224&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.9319&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="15712224">Odievre et al. (2005)</a> identified a homozygous mutation in the DLD gene (R447G; <a href="/entry/238331#0012">238331.0012</a>). E3 activity was about 20% of controls, and residual activity of the PDC and BCKDC were 63% and 56% of controls, respectively, which was likely sufficient to prevent accumulation of pyruvate and branched-chain amino acids. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1640293+15712224" 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="#4" class="mim-tip-reference" title="Craigen, W. J. &lt;strong&gt;Leigh disease with deficiency of lipoamide dehydrogenase: treatment failure with dichloroacetate.&lt;/strong&gt; Pediat. Neurol. 14: 69-71, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8652022/&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;8652022&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0887-8994(96)00005-7&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="8652022">Craigen (1996)</a> described a 6-month-old female infant who presented with hypotonia, ketolactic acidosis, and an MRI of the brain that showed subacute necrotizing encephalomyelopathy consistent with Leigh syndrome (LS; <a href="/entry/256000">256000</a>). Enzymatic analysis demonstrated deficiency of lipoamide dehydrogenase. Treatment with lipoic acid and later with dichloroacetate led to a significant but transient decline in serum lactate levels, but no clinical improvement. <a href="#5" class="mim-tip-reference" title="Hong, Y. S., Kerr, D. S., Craigen, W. J., Tan, J., Pan, Y., Lusk, M., Patel, M. S. &lt;strong&gt;Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency.&lt;/strong&gt; Hum. Molec. Genet. 5: 1925-1930, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8968745/&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;8968745&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/5.12.1925&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="8968745">Hong et al. (1996)</a> also studied the patient reported by <a href="#4" class="mim-tip-reference" title="Craigen, W. J. &lt;strong&gt;Leigh disease with deficiency of lipoamide dehydrogenase: treatment failure with dichloroacetate.&lt;/strong&gt; Pediat. Neurol. 14: 69-71, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8652022/&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;8652022&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0887-8994(96)00005-7&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="8652022">Craigen (1996)</a>. She had developmental delay, hypotonia, metabolic acidosis, transient neonatal hypoglycemia, and poor sucking. Plasma amino acid analysis in the patient initially showed increased branched-chain amino acids, and urinary organic acid analysis showed mild to moderate increases of lactic, 2-hydroxybutyric, 3-hydroxybutyric, alpha-ketoglutaric, and 3-hydroxyisovaleric acids. She died at age 28 months. Activities of the PDC and E3 in patient lymphocytes were 26% and 2% of control values, respectively, and in patient fibroblasts were 11% and 14%, respectively. KGDC activity in fibroblasts was 20%. Corresponding values in the clinically unaffected parents were about 50% of normal, except for KGDC, which was normal. These findings suggested that a partial reduction in E3 is not rate-limiting for KGDC activity in fibroblasts. Glycine was also not increased in the patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8652022+8968745" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Shany, E., Saada, A., Landau, D., Shaag, A., Hershkovitz, E., Elpeleg, O. N. &lt;strong&gt;Lipoamide dehydrogenase deficiency due to a novel mutation in the interface domain.&lt;/strong&gt; Biochem. Biophys. Res. Commun. 262: 163-166, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10448086/&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;10448086&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1006/bbrc.1999.1133&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="10448086">Shany et al. (1999)</a> reported a 9-month-old girl of Muslim origin with a severe neurodegenerative form of DLDD. She presented on the third day of life with apathy, poor feeding, and lethargy. Laboratory studies showed hypoglycemia and severe lactic acidosis, but normal levels of branched-chain keto acids and alpha-ketoglutarate. Muscle biopsy showed no activity of the pyruvate dehydrogenase complex, severely decreased activity of the alpha-ketoglutarate dehydrogenase complex (2%), and decreased DLD activity at 15% of controls. Each unaffected parent had about 50% reduced DLD protein activity. The patient had recurrent episodes of metabolic acidosis, often triggered by infection. Clinical features included microcephaly, lack of psychomotor development, blindness, deafness, hypotonia, brisk reflexes, and mild hypertrophic cardiomyopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10448086" 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="Hong, Y. S., Korman, S. H., Lee, J., Ghoshal, P., Wu, Q., Barash, V., Kang, S., Oh, S., Kwon, M., Gutman, A., Rachmel, A., Patel, M. S. &lt;strong&gt;Identification of a common mutation (Gly194Cys) in both Arab Moslem and Ashkenazi Jewish patients with dihydrolipoamide dehydrogenase (E3) deficiency: possible beneficial effect of vitamin therapy.&lt;/strong&gt; J. Inherit. Metab. Dis. 26: 816-818, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14765544/&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;14765544&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1023/b:boli.0000010004.12053.5b&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="14765544">Hong et al. (2003)</a> described 4 patients with DLD deficiency. Two were a sister and brother, born of consanguineous Palestinian Arab Muslim parents. The sister died in infancy during an episode of repeated vomiting associated with encephalopathy. Two earlier-born sibs had died under similar circumstances. Her brother had recurrent episodes of vomiting associated with encephalopathy from age 8 months. Examination at age 10 years showed generalized muscle weakness and wasting, ataxic gait, hepatomegaly, and lactic acidemia. He was treated with riboflavin, coenzyme Q, biotin, and carnitine. Six years later, he was functioning well at a normal school, but had slight ataxia and intention tremor. The 2 other patients, both of Ashkenazi Jewish descent, had a severe form of E3 deficiency. One had repeated episodes of hypoglycemia and was in a persistent vegetative state at age 4 years; he died soon after. A girl had recurrent episodes of repeated vomiting and acidosis since infancy; she died of hepatic failure at age 5 years. All 4 patients, including the Arab sibs, were homozygous for a G229C mutation (<a href="/entry/238331#0006">238331.0006</a>) that is a founder allele among Ashkenazi Jews. All patients had decreased levels of the E3 protein (range, 35-68% of controls) and decreased E3 activity (8 to 33% of controls). <a href="#6" class="mim-tip-reference" title="Hong, Y. S., Korman, S. H., Lee, J., Ghoshal, P., Wu, Q., Barash, V., Kang, S., Oh, S., Kwon, M., Gutman, A., Rachmel, A., Patel, M. S. &lt;strong&gt;Identification of a common mutation (Gly194Cys) in both Arab Moslem and Ashkenazi Jewish patients with dihydrolipoamide dehydrogenase (E3) deficiency: possible beneficial effect of vitamin therapy.&lt;/strong&gt; J. Inherit. Metab. Dis. 26: 816-818, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/14765544/&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;14765544&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1023/b:boli.0000010004.12053.5b&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="14765544">Hong et al. (2003)</a> emphasized the favorable outcome in the 1 child treated with riboflavin and additional supplements. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14765544" 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="Cameron, J. M., Levandovskiy, V., MacKay, N., Raiman, J., Renaud, D. L., Clarke, J. T. R., Feigenbaum, A., Elpeleg, O., Robinson, B. H. &lt;strong&gt;Novel mutations in dihydrolipoamide dehydrogenase deficiency in two cousins with borderline-normal PDH complex activity.&lt;/strong&gt; Am. J. Med. Genet. 140A: 1542-1552, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16770810/&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;16770810&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.31313&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="16770810">Cameron et al. (2006)</a> reported 2 second-cousin Ashkenazi Jewish boys with DLD deficiency. They had different genotypes and variable severity. One presented on the second day of life with metabolic acidosis and seizures, and showed episodes of myocardial and hepatic dysfunction, but had a relatively mild course of recurrent encephalopathy up to 8.5 years of age. The other presented at age 14 months with developmental delay, hypotonia, weakness, and microcephaly, and had multiple episodes of decompensation. Both patients had decreased activities of the KGDH (25% and 44%, respectively) and BCKDH (58% and 62%, respectively) complexes, but PDH complex activity was at the low end of normal (69% and 59%, respectively). DLD activity was decreased in both patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16770810" 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="#16" class="mim-tip-reference" title="Shaag, A., Saada, A., Berger, I., Mandel, H., Joseph, A., Feigenbaum, A., Elpeleg, O. N. &lt;strong&gt;Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews.&lt;/strong&gt; Am. J. Med. Genet. 82: 177-182, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9934985/&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;9934985&lt;/a&gt;]" pmid="9934985">Shaag et al. (1999)</a> studied 13 patients with E3 deficiency originating from 7 Ashkenazi Jewish families. The disease course was highly variable, with a variable age at onset. Some patients had few neurologic sequelae and long survival. Two patients presented immediately after birth, 9 around age 2 years, and 2 as adults. All had recurrent episodes of vomiting, abdominal pain, and hepatomegaly, usually associated with neurologic signs during the episodes. Episodes were associated with lactic acidosis, abnormal liver enzymes, and prolonged prothrombin time. Biochemical anomalies, such as increased branched-chain amino acids and increased alpha-ketoacids, were not commonly found. The 2 patients who presented neonatally had residual neurologic damage with attention deficit-hyperactivity disorder, mild ataxia, motor incoordination, muscle hypotonia, and weakness. Nine patients who presented in early childhood or as adults suffered from exertional fatigue between episodes of decompensation but were otherwise asymptomatic and showed normal psychomotor development. Two patients died because of intractable metabolic acidosis and multiorgan failure. In all patients E3 activity was reduced to 8 to 21% of the control value in muscle or lymphocytes. In 4 patients tested, the E3 protein in muscle was reduced to 20 to 60% of control. Eleven patients were homozygous for a founder mutation in the DLD gene (G229C; <a href="/entry/238331#0006">238331.0006</a>) and 2 were compound heterozygous for G229C and a 1-bp insertion (<a href="/entry/238331#0003">238331.0003</a>). <a href="#16" class="mim-tip-reference" title="Shaag, A., Saada, A., Berger, I., Mandel, H., Joseph, A., Feigenbaum, A., Elpeleg, O. N. &lt;strong&gt;Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews.&lt;/strong&gt; Am. J. Med. Genet. 82: 177-182, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9934985/&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;9934985&lt;/a&gt;]" pmid="9934985">Shaag et al. (1999)</a> concluded that the phenotype associated with G229C is milder than that associated with other genotypes. However, the phenotype did not appear to be associated with residual enzyme activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9934985" 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="inheritance" class="mim-anchor"></a>
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<strong>Inheritance</strong>
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<p>The transmission pattern of DLD deficiency in the families reported by <a href="#16" class="mim-tip-reference" title="Shaag, A., Saada, A., Berger, I., Mandel, H., Joseph, A., Feigenbaum, A., Elpeleg, O. N. &lt;strong&gt;Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews.&lt;/strong&gt; Am. J. Med. Genet. 82: 177-182, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9934985/&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;9934985&lt;/a&gt;]" pmid="9934985">Shaag et al. (1999)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9934985" 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>
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>Molecular Genetics</strong>
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<p>In a patient with dihydrolipoyl dehydrogenase deficiency reported by <a href="#15" class="mim-tip-reference" title="Sakaguchi, Y., Yoshino, M., Aramaki, S., Yoshida, I., Yamashita, F., Kuhara, T., Matsumoto, I., Hayashi, T. &lt;strong&gt;Dihydrolipoyl dehydrogenase deficiency: a therapeutic trial with branched-chain amino acid restriction.&lt;/strong&gt; Europ. J. Pediat. 145: 271-274, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3769994/&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;3769994&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00439399&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="3769994">Sakaguchi et al. (1986)</a>, <a href="#7" class="mim-tip-reference" title="Liu, T.-C., Kim, H., Arizmendi, C., Kitano, A., Patel, M. S. &lt;strong&gt;Identification of two missense mutations in a dihydrolipoamide dehydrogenase-deficient patient.&lt;/strong&gt; Proc. Nat. Acad. Sci. 90: 5186-5190, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8506365/&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;8506365&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.90.11.5186&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="8506365">Liu et al. (1993)</a> demonstrated compound heterozygosity for 2 missense mutations in the DLD gene (K72E, <a href="/entry/238331#0001">238331.0001</a> and P488L, <a href="/entry/238331#0002">238331.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8506365+3769994" 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 female infant with E3 deficiency reported by <a href="#4" class="mim-tip-reference" title="Craigen, W. J. &lt;strong&gt;Leigh disease with deficiency of lipoamide dehydrogenase: treatment failure with dichloroacetate.&lt;/strong&gt; Pediat. Neurol. 14: 69-71, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8652022/&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;8652022&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0887-8994(96)00005-7&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="8652022">Craigen (1996)</a>, <a href="#5" class="mim-tip-reference" title="Hong, Y. S., Kerr, D. S., Craigen, W. J., Tan, J., Pan, Y., Lusk, M., Patel, M. S. &lt;strong&gt;Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency.&lt;/strong&gt; Hum. Molec. Genet. 5: 1925-1930, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8968745/&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;8968745&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/5.12.1925&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="8968745">Hong et al. (1996)</a> identified compound heterozygosity for 2 mutations in the DLD gene (c.105insA, <a href="/entry/238331#0003">238331.0003</a> and R495G, <a href="/entry/238331#0004">238331.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8652022+8968745" 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 second-cousin Ashkenazi Jewish patients with DLD deficiency, <a href="#2" class="mim-tip-reference" title="Cameron, J. M., Levandovskiy, V., MacKay, N., Raiman, J., Renaud, D. L., Clarke, J. T. R., Feigenbaum, A., Elpeleg, O., Robinson, B. H. &lt;strong&gt;Novel mutations in dihydrolipoamide dehydrogenase deficiency in two cousins with borderline-normal PDH complex activity.&lt;/strong&gt; Am. J. Med. Genet. 140A: 1542-1552, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16770810/&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;16770810&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.31313&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="16770810">Cameron et al. (2006)</a> identified compound heterozygosity for 2 mutations in the DLD gene. Both patients carried an I47T mutation (<a href="/entry/238331#0013">238331.0013</a>) on 1 allele; on the other allele, one had a G229C mutation (<a href="/entry/238331#0006">238331.0006</a>) and the other had an E375K (<a href="/entry/238331#0009">238331.0009</a>) mutation. All of the parents were unaffected and heterozygous for 1 of the mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16770810" 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>
</span>
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<div>
<a id="populationGenetics" class="mim-anchor"></a>
<h4 href="#mimPopulationGeneticsFold" id="mimPopulationGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimPopulationGeneticsToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
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<strong>Population Genetics</strong>
</span>
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<div id="mimPopulationGeneticsFold" class="collapse in mimTextToggleFold">
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<p>Among 13 affected patients from 7 Ashkenazi Jewish families with lipoamide dehydrogenase deficiency, <a href="#16" class="mim-tip-reference" title="Shaag, A., Saada, A., Berger, I., Mandel, H., Joseph, A., Feigenbaum, A., Elpeleg, O. N. &lt;strong&gt;Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews.&lt;/strong&gt; Am. J. Med. Genet. 82: 177-182, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9934985/&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;9934985&lt;/a&gt;]" pmid="9934985">Shaag et al. (1999)</a> identified a founder mutation (G229C; <a href="/entry/238331#0006">238331.0006</a>) in the DLD gene in 12 of 14 mutated alleles. The other 2 alleles had the previously identified c.105insA mutation (<a href="/entry/238331#0003">238331.0003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9934985" 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="references"class="mim-anchor"></a>
<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span class="mim-font">
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<strong>REFERENCES</strong>
</span>
</h4>
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<p />
</div>
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
<ol>
<li>
<a id="1" class="mim-anchor"></a>
<a id="Bonnefont1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bonnefont, J.-P., Chretien, D., Rustin, P., Robinson, B., Vassault, A., Aupetit, J., Charpentier, C., Rabier, D., Saudubray, J.-M., Munnich, A.
<strong>Alpha-ketoglutarate dehydrogenase deficiency presenting as congenital lactic acidosis.</strong>
J. Pediat. 121: 255-258, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1640293/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1640293</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1640293" 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/s0022-3476(05)81199-0" target="_blank">Full Text</a>]
</p>
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<li>
<a id="2" class="mim-anchor"></a>
<a id="Cameron2006" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Cameron, J. M., Levandovskiy, V., MacKay, N., Raiman, J., Renaud, D. L., Clarke, J. T. R., Feigenbaum, A., Elpeleg, O., Robinson, B. H.
<strong>Novel mutations in dihydrolipoamide dehydrogenase deficiency in two cousins with borderline-normal PDH complex activity.</strong>
Am. J. Med. Genet. 140A: 1542-1552, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16770810/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16770810</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16770810" 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.31313" target="_blank">Full Text</a>]
</p>
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<a id="3" class="mim-anchor"></a>
<a id="Chuang2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Chuang, D. T., Shih, V. E.
<strong>Maple syrup urine disease (branched-chain ketoaciduria). In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. II. (8th ed.)</strong>
New York: McGraw-Hill (pub.) 2001. Pp. 1971-2005.
</p>
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<a id="4" class="mim-anchor"></a>
<a id="Craigen1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Craigen, W. J.
<strong>Leigh disease with deficiency of lipoamide dehydrogenase: treatment failure with dichloroacetate.</strong>
Pediat. Neurol. 14: 69-71, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8652022/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8652022</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8652022" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/0887-8994(96)00005-7" target="_blank">Full Text</a>]
</p>
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<li>
<a id="5" class="mim-anchor"></a>
<a id="Hong1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hong, Y. S., Kerr, D. S., Craigen, W. J., Tan, J., Pan, Y., Lusk, M., Patel, M. S.
<strong>Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency.</strong>
Hum. Molec. Genet. 5: 1925-1930, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8968745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8968745</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8968745" 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/hmg/5.12.1925" target="_blank">Full Text</a>]
</p>
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<a id="6" class="mim-anchor"></a>
<a id="Hong2003" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hong, Y. S., Korman, S. H., Lee, J., Ghoshal, P., Wu, Q., Barash, V., Kang, S., Oh, S., Kwon, M., Gutman, A., Rachmel, A., Patel, M. S.
<strong>Identification of a common mutation (Gly194Cys) in both Arab Moslem and Ashkenazi Jewish patients with dihydrolipoamide dehydrogenase (E3) deficiency: possible beneficial effect of vitamin therapy.</strong>
J. Inherit. Metab. Dis. 26: 816-818, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/14765544/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">14765544</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=14765544" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1023/b:boli.0000010004.12053.5b" target="_blank">Full Text</a>]
</p>
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<a id="7" class="mim-anchor"></a>
<a id="Liu1993" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Liu, T.-C., Kim, H., Arizmendi, C., Kitano, A., Patel, M. S.
<strong>Identification of two missense mutations in a dihydrolipoamide dehydrogenase-deficient patient.</strong>
Proc. Nat. Acad. Sci. 90: 5186-5190, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8506365/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8506365</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8506365" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.90.11.5186" target="_blank">Full Text</a>]
</p>
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<a id="8" class="mim-anchor"></a>
<a id="Matalon1981" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Matalon, R., Michals, K., Stumpf, D., Goodman, S., Parks, J.
<strong>Lactic acidosis due to lipoamide dehydrogenase (LAD) deficiency: improvement after oral lipoic acid. (Abstract)</strong>
Am. J. Hum. Genet. 33: 48A, 1981.
</p>
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Munnich, A., Saudubray, J. M., Taylor, J., Charpentier, C., Marsac, C., Rocchiccioli, F., Amedee-Manesme, O., Coude, F. X., Frezal, J., Robinson, B. H.
<strong>Congenital lactic acidosis, alpha-ketoglutaric aciduria and variant form of maple syrup urine disease due to a single enzyme defect: dihydrolipoyl dehydrogenase deficiency.</strong>
Acta Paediat. Scand. 71: 167-171, 1982.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6897145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6897145</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6897145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1651-2227.1982.tb09393.x" target="_blank">Full Text</a>]
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<a id="Odievre2005" class="mim-anchor"></a>
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Odievre, M. H., Chretien, D., Munnich, A., Robinson, B. H., Dumoulin, R., Masmoudi, S., Kadhom, N., Rotig, A., Rustin, P., Bonnefont, J. P.
<strong>A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency.</strong>
Hum. Mutat. 25: 323-324, 2005.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15712224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15712224</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15712224" 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/humu.9319" target="_blank">Full Text</a>]
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<a id="Robinson1981" class="mim-anchor"></a>
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Robinson, B. H., Sherwood, W. G., Kahler, S., O'Flynn, M. E., Nadler, H.
<strong>Lipoamide dehydrogenase deficiency. (Letter)</strong>
New Eng. J. Med. 304: 53-54, 1981.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6893619/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6893619</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6893619" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM198101013040116" target="_blank">Full Text</a>]
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<a id="Robinson1981" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Robinson, B. H., Taylor, J., Kahler, S. G., Kirkman, H. N.
<strong>Lactic acidemia, neurologic deterioration and carbohydrate dependence in a girl with dihydrolipoyl dehydrogenase deficiency.</strong>
Europ. J. Pediat. 136: 35-39, 1981.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6894281/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6894281</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6894281" 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/BF00441708" target="_blank">Full Text</a>]
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<a id="13" class="mim-anchor"></a>
<a id="Robinson1977" class="mim-anchor"></a>
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Robinson, B. H., Taylor, J., Sherwood, W. G.
<strong>Deficiency of dihydrolipoyl dehydrogenase (a component of the pyruvate and alpha-ketoglutarate dehydrogenase complexes): a cause of congenital lactic acidosis in infancy.</strong>
Pediat. Res. 11: 1198-1202, 1977.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/413089/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">413089</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=413089" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1203/00006450-197712000-00006" target="_blank">Full Text</a>]
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<a id="Robinson2001" class="mim-anchor"></a>
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Robinson, B. H.
<strong>Lactic acidemia: disorders of pyruvate carboxylase and pyruvate dehydrogenase. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. II. (8th ed.)</strong>
New York: McGraw-Hill (pub.) 2001. Pp. 2275-2295.
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<a id="Sakaguchi1986" class="mim-anchor"></a>
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Sakaguchi, Y., Yoshino, M., Aramaki, S., Yoshida, I., Yamashita, F., Kuhara, T., Matsumoto, I., Hayashi, T.
<strong>Dihydrolipoyl dehydrogenase deficiency: a therapeutic trial with branched-chain amino acid restriction.</strong>
Europ. J. Pediat. 145: 271-274, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3769994/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3769994</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3769994" 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/BF00439399" target="_blank">Full Text</a>]
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<a id="Shaag1999" class="mim-anchor"></a>
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Shaag, A., Saada, A., Berger, I., Mandel, H., Joseph, A., Feigenbaum, A., Elpeleg, O. N.
<strong>Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews.</strong>
Am. J. Med. Genet. 82: 177-182, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9934985/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9934985</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9934985" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Shany1999" class="mim-anchor"></a>
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Shany, E., Saada, A., Landau, D., Shaag, A., Hershkovitz, E., Elpeleg, O. N.
<strong>Lipoamide dehydrogenase deficiency due to a novel mutation in the interface domain.</strong>
Biochem. Biophys. Res. Commun. 262: 163-166, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10448086/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10448086</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10448086" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1006/bbrc.1999.1133" target="_blank">Full Text</a>]
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Cassandra L. Kniffin - updated : 2/28/2013
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Cassandra L. Kniffin - updated : 7/8/2004<br>Cassandra L. Kniffin - updated : 4/1/2004<br>Natalie E. Krasikov - updated : 3/29/2004<br>Cassandra L. Kniffin - updated : 1/28/2004<br>Carol A. Bocchini - updated : 4/5/1999<br>Victor A. McKusick - updated : 2/14/1999<br>Victor A. McKusick - updated : 10/10/1997<br>Moyra Smith - updated : 1/29/1997<br>Orest Hurko - updated : 5/17/1996<br>Orest Hurko - updated : 5/16/1996
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Victor A. McKusick : 6/3/1986
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carol : 05/13/2024
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<h3>
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<strong>#</strong> 246900
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<span class="mim-font">
DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY; DLDD
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<em>Alternative titles; symbols</em>
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<span class="mim-font">
DLD DEFICIENCY<br />
E3 DEFICIENCY<br />
LIPOAMIDE DEHYDROGENASE DEFICIENCY, LACTIC ACIDOSIS DUE TO<br />
MAPLE SYRUP URINE DISEASE, TYPE III; MSUD3
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<strong>SNOMEDCT:</strong> 29914000; &nbsp;
<strong>ORPHA:</strong> 2394, 765; &nbsp;
<strong>DO:</strong> 9269; &nbsp;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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<span class="mim-font">
7q31.1
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<span class="mim-font">
Dihydrolipoamide dehydrogenase deficiency
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246900
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Autosomal recessive
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3
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DLD
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238331
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because dihydrolipoamide dehydrogenase deficiency (DLDD) is caused by homozygous or compound heterozygous mutation in the DLD gene (238331) on chromosome 7q31.</p>
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<strong>Description</strong>
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<p>Dihydrolipoamide dehydrogenase deficiency (DLDD) is an autosomal recessive metabolic disorder characterized biochemically by a combined deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), pyruvate dehydrogenase complex (PDC), and alpha-ketoglutarate dehydrogenase complex (KGDC). This is the result of E3 being a common component of all 3 mitochondrial multienzyme complexes. Clinically, affected individuals have lactic acidosis and neurologic deterioration due to sensitivity of the central nervous system to defects in oxidative metabolism. E3 deficiency is often associated with increased urinary excretion of alpha-keto acids, such as pyruvate (summary by Hong et al., 1996). E3 deficiency can also be associated with increased concentrations of branched-chain amino acids, as observed in maple syrup urine disease (MSUD; 248600), and is sometimes referred to as 'MSUD type III,' although patients with E3 deficiency have additional biochemical defects (Chuang and Shih, 2001; Robinson, 2001). </p>
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<strong>Clinical Features</strong>
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<p>Robinson et al. (1977) reported a male child, born of Caucasian first-cousin parents, who died at age 7 months with progressive neurologic deterioration and persistent metabolic acidosis. He was well until age 8 weeks, when he abruptly became ill with irregular labored respiration, increased muscle tone, bilateral optic atrophy, and metabolic acidosis. He had elevated blood pyruvate, lactate, alpha-ketoglutarate, and branched-chain amino acids, as well as occasional hypoglycemia. Thiamine therapy was of no benefit. Postmortem tissue analysis showed deficiency of the pyruvate dehydrogenase complex, and specifically of dihydrolipoyl dehydrogenase, or E3. Robinson et al. (1981) reported another similar case. The parents were normal in both cases, but the parents of 1 patient had decreased enzyme activity at about 30 to 42% of normal, supporting recessive inheritance. A primary deficiency of this enzyme had been suggested as the basic defect in Friedreich ataxia (229300), but Robinson et al. (1981) concluded that the deficiency in Friedreich ataxia is likely a secondary phenomenon. </p><p>In a case of E3 deficiency, Matalon et al. (1981) found that oral administration of lipoic acid resulted in almost complete clearance of abnormal organic aciduria and lactic and pyruvic acidemia, with clinical improvement. The patient had neonatal hypothermia, failure to thrive, and metabolic acidosis. In cultured fibroblasts, the E3 component was 23% of the control mean. Munnich et al. (1982) reported a 6-month-old girl with vomiting, hypotonia, and motor retardation who had combined chemical features of lactic acidosis, maple syrup urine disease, and ketoglutaric aciduria. E3 activity was reduced. </p><p>Sakaguchi et al. (1986) reported a patient with E3-deficient MSUD. In the first week of life, the patient's blood leucine was found to be 5 mg/dl, but the patient was left on a normal diet. At the age of 6 months, he exhibited hypotonia and minimal dystonic movements of the upper limbs. He had elevated plasma levels of pyruvate, alpha-ketoglutarate, and branched-chain amino acids and alpha-keto acids. Urinary excretion of these keto acids and their metabolites were also elevated. At 7 months of age, the patient was placed on a diet restricted in branched-chain amino acids, resulting in improvement of some biochemical and developmental parameters. The patient died at the age of 21 months, following a ketoacidotic episode. The total pyruvate dehydrogenase complex activity of the patient's cells was 10 to 30% that of control cells. Pyruvate dehydrogenase (E1) and dihydrolipoamide acetyltransferase (E2) activities were normal in the patient's muscle, but E3 activity was not detectable in either muscle or liver specimens obtained at autopsy. </p><p>In 3 males born to first-cousin Algerian parents and presenting with hypotonia, metabolic acidosis, and hyperlactatemia immediately after birth, Bonnefont et al. (1992) described a 'new' inborn error of the tricarboxylic acid cycle, alpha-ketoglutarate dehydrogenase. Neurologic deterioration resulted in death at about 30 months of age. In a review of the patients reported by Bonnefont et al. (1992), Odievre et al. (2005) noted that 1 of the patients had hypertrophic cardiomyopathy. The patients showed lack of accumulation of branched-chain amino acids or pyruvate, but KGDC activity was markedly deficient. In fibroblasts derived from these patients, Odievre et al. (2005) identified a homozygous mutation in the DLD gene (R447G; 238331.0012). E3 activity was about 20% of controls, and residual activity of the PDC and BCKDC were 63% and 56% of controls, respectively, which was likely sufficient to prevent accumulation of pyruvate and branched-chain amino acids. </p><p>Craigen (1996) described a 6-month-old female infant who presented with hypotonia, ketolactic acidosis, and an MRI of the brain that showed subacute necrotizing encephalomyelopathy consistent with Leigh syndrome (LS; 256000). Enzymatic analysis demonstrated deficiency of lipoamide dehydrogenase. Treatment with lipoic acid and later with dichloroacetate led to a significant but transient decline in serum lactate levels, but no clinical improvement. Hong et al. (1996) also studied the patient reported by Craigen (1996). She had developmental delay, hypotonia, metabolic acidosis, transient neonatal hypoglycemia, and poor sucking. Plasma amino acid analysis in the patient initially showed increased branched-chain amino acids, and urinary organic acid analysis showed mild to moderate increases of lactic, 2-hydroxybutyric, 3-hydroxybutyric, alpha-ketoglutaric, and 3-hydroxyisovaleric acids. She died at age 28 months. Activities of the PDC and E3 in patient lymphocytes were 26% and 2% of control values, respectively, and in patient fibroblasts were 11% and 14%, respectively. KGDC activity in fibroblasts was 20%. Corresponding values in the clinically unaffected parents were about 50% of normal, except for KGDC, which was normal. These findings suggested that a partial reduction in E3 is not rate-limiting for KGDC activity in fibroblasts. Glycine was also not increased in the patient. </p><p>Shany et al. (1999) reported a 9-month-old girl of Muslim origin with a severe neurodegenerative form of DLDD. She presented on the third day of life with apathy, poor feeding, and lethargy. Laboratory studies showed hypoglycemia and severe lactic acidosis, but normal levels of branched-chain keto acids and alpha-ketoglutarate. Muscle biopsy showed no activity of the pyruvate dehydrogenase complex, severely decreased activity of the alpha-ketoglutarate dehydrogenase complex (2%), and decreased DLD activity at 15% of controls. Each unaffected parent had about 50% reduced DLD protein activity. The patient had recurrent episodes of metabolic acidosis, often triggered by infection. Clinical features included microcephaly, lack of psychomotor development, blindness, deafness, hypotonia, brisk reflexes, and mild hypertrophic cardiomyopathy. </p><p>Hong et al. (2003) described 4 patients with DLD deficiency. Two were a sister and brother, born of consanguineous Palestinian Arab Muslim parents. The sister died in infancy during an episode of repeated vomiting associated with encephalopathy. Two earlier-born sibs had died under similar circumstances. Her brother had recurrent episodes of vomiting associated with encephalopathy from age 8 months. Examination at age 10 years showed generalized muscle weakness and wasting, ataxic gait, hepatomegaly, and lactic acidemia. He was treated with riboflavin, coenzyme Q, biotin, and carnitine. Six years later, he was functioning well at a normal school, but had slight ataxia and intention tremor. The 2 other patients, both of Ashkenazi Jewish descent, had a severe form of E3 deficiency. One had repeated episodes of hypoglycemia and was in a persistent vegetative state at age 4 years; he died soon after. A girl had recurrent episodes of repeated vomiting and acidosis since infancy; she died of hepatic failure at age 5 years. All 4 patients, including the Arab sibs, were homozygous for a G229C mutation (238331.0006) that is a founder allele among Ashkenazi Jews. All patients had decreased levels of the E3 protein (range, 35-68% of controls) and decreased E3 activity (8 to 33% of controls). Hong et al. (2003) emphasized the favorable outcome in the 1 child treated with riboflavin and additional supplements. </p><p>Cameron et al. (2006) reported 2 second-cousin Ashkenazi Jewish boys with DLD deficiency. They had different genotypes and variable severity. One presented on the second day of life with metabolic acidosis and seizures, and showed episodes of myocardial and hepatic dysfunction, but had a relatively mild course of recurrent encephalopathy up to 8.5 years of age. The other presented at age 14 months with developmental delay, hypotonia, weakness, and microcephaly, and had multiple episodes of decompensation. Both patients had decreased activities of the KGDH (25% and 44%, respectively) and BCKDH (58% and 62%, respectively) complexes, but PDH complex activity was at the low end of normal (69% and 59%, respectively). DLD activity was decreased in both patients. </p><p><strong><em>Clinical Variability</em></strong></p><p>
Shaag et al. (1999) studied 13 patients with E3 deficiency originating from 7 Ashkenazi Jewish families. The disease course was highly variable, with a variable age at onset. Some patients had few neurologic sequelae and long survival. Two patients presented immediately after birth, 9 around age 2 years, and 2 as adults. All had recurrent episodes of vomiting, abdominal pain, and hepatomegaly, usually associated with neurologic signs during the episodes. Episodes were associated with lactic acidosis, abnormal liver enzymes, and prolonged prothrombin time. Biochemical anomalies, such as increased branched-chain amino acids and increased alpha-ketoacids, were not commonly found. The 2 patients who presented neonatally had residual neurologic damage with attention deficit-hyperactivity disorder, mild ataxia, motor incoordination, muscle hypotonia, and weakness. Nine patients who presented in early childhood or as adults suffered from exertional fatigue between episodes of decompensation but were otherwise asymptomatic and showed normal psychomotor development. Two patients died because of intractable metabolic acidosis and multiorgan failure. In all patients E3 activity was reduced to 8 to 21% of the control value in muscle or lymphocytes. In 4 patients tested, the E3 protein in muscle was reduced to 20 to 60% of control. Eleven patients were homozygous for a founder mutation in the DLD gene (G229C; 238331.0006) and 2 were compound heterozygous for G229C and a 1-bp insertion (238331.0003). Shaag et al. (1999) concluded that the phenotype associated with G229C is milder than that associated with other genotypes. However, the phenotype did not appear to be associated with residual enzyme activity. </p>
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<h4>
<span class="mim-font">
<strong>Inheritance</strong>
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</h4>
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<span class="mim-text-font">
<p>The transmission pattern of DLD deficiency in the families reported by Shaag et al. (1999) was consistent with autosomal recessive inheritance. </p>
</span>
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</div>
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<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
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</h4>
</div>
<span class="mim-text-font">
<p>In a patient with dihydrolipoyl dehydrogenase deficiency reported by Sakaguchi et al. (1986), Liu et al. (1993) demonstrated compound heterozygosity for 2 missense mutations in the DLD gene (K72E, 238331.0001 and P488L, 238331.0002). </p><p>In a female infant with E3 deficiency reported by Craigen (1996), Hong et al. (1996) identified compound heterozygosity for 2 mutations in the DLD gene (c.105insA, 238331.0003 and R495G, 238331.0004). </p><p>In 2 second-cousin Ashkenazi Jewish patients with DLD deficiency, Cameron et al. (2006) identified compound heterozygosity for 2 mutations in the DLD gene. Both patients carried an I47T mutation (238331.0013) on 1 allele; on the other allele, one had a G229C mutation (238331.0006) and the other had an E375K (238331.0009) mutation. All of the parents were unaffected and heterozygous for 1 of the mutations. </p>
</span>
<div>
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</div>
<div>
<h4>
<span class="mim-font">
<strong>Population Genetics</strong>
</span>
</h4>
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<span class="mim-text-font">
<p>Among 13 affected patients from 7 Ashkenazi Jewish families with lipoamide dehydrogenase deficiency, Shaag et al. (1999) identified a founder mutation (G229C; 238331.0006) in the DLD gene in 12 of 14 mutated alleles. The other 2 alleles had the previously identified c.105insA mutation (238331.0003). </p>
</span>
<div>
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</div>
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<div>
<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div>
<ol>
<li>
<p class="mim-text-font">
Bonnefont, J.-P., Chretien, D., Rustin, P., Robinson, B., Vassault, A., Aupetit, J., Charpentier, C., Rabier, D., Saudubray, J.-M., Munnich, A.
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Cameron, J. M., Levandovskiy, V., MacKay, N., Raiman, J., Renaud, D. L., Clarke, J. T. R., Feigenbaum, A., Elpeleg, O., Robinson, B. H.
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Chuang, D. T., Shih, V. E.
<strong>Maple syrup urine disease (branched-chain ketoaciduria). In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. II. (8th ed.)</strong>
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</p>
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<li>
<p class="mim-text-font">
Craigen, W. J.
<strong>Leigh disease with deficiency of lipoamide dehydrogenase: treatment failure with dichloroacetate.</strong>
Pediat. Neurol. 14: 69-71, 1996.
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Hong, Y. S., Kerr, D. S., Craigen, W. J., Tan, J., Pan, Y., Lusk, M., Patel, M. S.
<strong>Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency.</strong>
Hum. Molec. Genet. 5: 1925-1930, 1996.
[PubMed: 8968745]
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</p>
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<p class="mim-text-font">
Hong, Y. S., Korman, S. H., Lee, J., Ghoshal, P., Wu, Q., Barash, V., Kang, S., Oh, S., Kwon, M., Gutman, A., Rachmel, A., Patel, M. S.
<strong>Identification of a common mutation (Gly194Cys) in both Arab Moslem and Ashkenazi Jewish patients with dihydrolipoamide dehydrogenase (E3) deficiency: possible beneficial effect of vitamin therapy.</strong>
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[PubMed: 14765544]
[Full Text: https://doi.org/10.1023/b:boli.0000010004.12053.5b]
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Liu, T.-C., Kim, H., Arizmendi, C., Kitano, A., Patel, M. S.
<strong>Identification of two missense mutations in a dihydrolipoamide dehydrogenase-deficient patient.</strong>
Proc. Nat. Acad. Sci. 90: 5186-5190, 1993.
[PubMed: 8506365]
[Full Text: https://doi.org/10.1073/pnas.90.11.5186]
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<p class="mim-text-font">
Matalon, R., Michals, K., Stumpf, D., Goodman, S., Parks, J.
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Am. J. Hum. Genet. 33: 48A, 1981.
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<p class="mim-text-font">
Munnich, A., Saudubray, J. M., Taylor, J., Charpentier, C., Marsac, C., Rocchiccioli, F., Amedee-Manesme, O., Coude, F. X., Frezal, J., Robinson, B. H.
<strong>Congenital lactic acidosis, alpha-ketoglutaric aciduria and variant form of maple syrup urine disease due to a single enzyme defect: dihydrolipoyl dehydrogenase deficiency.</strong>
Acta Paediat. Scand. 71: 167-171, 1982.
[PubMed: 6897145]
[Full Text: https://doi.org/10.1111/j.1651-2227.1982.tb09393.x]
</p>
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<p class="mim-text-font">
Odievre, M. H., Chretien, D., Munnich, A., Robinson, B. H., Dumoulin, R., Masmoudi, S., Kadhom, N., Rotig, A., Rustin, P., Bonnefont, J. P.
<strong>A novel mutation in the dihydrolipoamide dehydrogenase E3 subunit gene (DLD) resulting in an atypical form of alpha-ketoglutarate dehydrogenase deficiency.</strong>
Hum. Mutat. 25: 323-324, 2005.
[PubMed: 15712224]
[Full Text: https://doi.org/10.1002/humu.9319]
</p>
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<p class="mim-text-font">
Robinson, B. H., Sherwood, W. G., Kahler, S., O'Flynn, M. E., Nadler, H.
<strong>Lipoamide dehydrogenase deficiency. (Letter)</strong>
New Eng. J. Med. 304: 53-54, 1981.
[PubMed: 6893619]
[Full Text: https://doi.org/10.1056/NEJM198101013040116]
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<li>
<p class="mim-text-font">
Robinson, B. H., Taylor, J., Kahler, S. G., Kirkman, H. N.
<strong>Lactic acidemia, neurologic deterioration and carbohydrate dependence in a girl with dihydrolipoyl dehydrogenase deficiency.</strong>
Europ. J. Pediat. 136: 35-39, 1981.
[PubMed: 6894281]
[Full Text: https://doi.org/10.1007/BF00441708]
</p>
</li>
<li>
<p class="mim-text-font">
Robinson, B. H., Taylor, J., Sherwood, W. G.
<strong>Deficiency of dihydrolipoyl dehydrogenase (a component of the pyruvate and alpha-ketoglutarate dehydrogenase complexes): a cause of congenital lactic acidosis in infancy.</strong>
Pediat. Res. 11: 1198-1202, 1977.
[PubMed: 413089]
[Full Text: https://doi.org/10.1203/00006450-197712000-00006]
</p>
</li>
<li>
<p class="mim-text-font">
Robinson, B. H.
<strong>Lactic acidemia: disorders of pyruvate carboxylase and pyruvate dehydrogenase. In: Scriver, C. R.; Beaudet, A. L.; Sly, W. S.; Valle, D. (eds.): The Metabolic and Molecular Bases of Inherited Disease. Vol. II. (8th ed.)</strong>
New York: McGraw-Hill (pub.) 2001. Pp. 2275-2295.
</p>
</li>
<li>
<p class="mim-text-font">
Sakaguchi, Y., Yoshino, M., Aramaki, S., Yoshida, I., Yamashita, F., Kuhara, T., Matsumoto, I., Hayashi, T.
<strong>Dihydrolipoyl dehydrogenase deficiency: a therapeutic trial with branched-chain amino acid restriction.</strong>
Europ. J. Pediat. 145: 271-274, 1986.
[PubMed: 3769994]
[Full Text: https://doi.org/10.1007/BF00439399]
</p>
</li>
<li>
<p class="mim-text-font">
Shaag, A., Saada, A., Berger, I., Mandel, H., Joseph, A., Feigenbaum, A., Elpeleg, O. N.
<strong>Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews.</strong>
Am. J. Med. Genet. 82: 177-182, 1999.
[PubMed: 9934985]
</p>
</li>
<li>
<p class="mim-text-font">
Shany, E., Saada, A., Landau, D., Shaag, A., Hershkovitz, E., Elpeleg, O. N.
<strong>Lipoamide dehydrogenase deficiency due to a novel mutation in the interface domain.</strong>
Biochem. Biophys. Res. Commun. 262: 163-166, 1999.
[PubMed: 10448086]
[Full Text: https://doi.org/10.1006/bbrc.1999.1133]
</p>
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