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<title>
Entry
- #124000 - MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 1; MC3DN1
- OMIM
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<span class="h4">#124000</span>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/124000"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS124000"> <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="#pathogenesis">Pathogenesis</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=(MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE) OR (BCS1L)" class="mim-tip-hint" title="Clinical Trials" 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=3378&Typ=Pat" title="Isolated complex III deficiency" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Isolated complex III defic…&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=19798&Typ=Pat" title="Renal tubulopathy-encephalopathy-liver failure syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Renal tubulopathy-encephal…&nbsp;</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/4825" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=124000[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1460" title="Isolated complex III deficiency" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Isolated complex III defic…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=254902" title="Renal tubulopathy-encephalopathy-liver failure syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Renal tubulopathy-encephal…</a></div>
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<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/19e53f14-1489-4355-ada1-25d9fcb55add/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
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<div style="display: table-cell;">Animal Models</div>
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<div><a href="https://www.alliancegenome.org/disease/DOID:0080111" 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/124000" 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:0080111" 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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<a id="title" class="mim-anchor"></a>
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<a id="number" class="mim-anchor"></a>
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>ORPHA:</strong> 1460, 254902<br />
<strong>DO:</strong> 0080111<br />
">ICD+</a>
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<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
124000
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<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 1; MC3DN1
</span>
</h3>
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<br />
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<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
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<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/2/1014?start=-3&limit=10&highlight=1014">
2q35
</a>
</span>
</td>
<td>
<span class="mim-font">
Mitochondrial complex III deficiency, nuclear type 1
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/124000"> 124000 </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">
BCS1L
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603647"> 603647 </a>
</span>
</td>
</tr>
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<li><a href="/graph/linear/124000" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<p />
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
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<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GROWTH </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Other </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Failure to thrive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/432788009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">432788009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/54840006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">54840006</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0015544&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015544</a>, <a href="https://bioportal.bioontology.org/search?q=C2315100&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2315100</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span><br /> -
Poor prenatal growth <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22033007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22033007</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/764.90" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">764.90</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/764.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">764.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0015934&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015934</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001511" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001511</a>]</span><br /> -
Poor postnatal growth <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1852375&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1852375</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Ears </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Deafness (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/343087000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">343087000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H91.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H91.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018772&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018772</a>, <a href="https://bioportal.bioontology.org/search?q=C0011053&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011053</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000365" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000365</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000365" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000365</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Cataracts (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/193570009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">193570009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/247053007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">247053007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95722004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95722004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H26.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H26.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/366" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">366</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/366.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">366.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0086543&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0086543</a>, <a href="https://bioportal.bioontology.org/search?q=C0521707&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0521707</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000518" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000518</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000518" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000518</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">
- Decreased liver function <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/77981007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">77981007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0232744&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0232744</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>]</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 /> -
Biopsy shows fibrosis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1852376&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1852376</a>]</span><br /> -
Cholestasis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/30144000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">30144000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/33688009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">33688009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/197446008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">197446008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K83.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K83.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/576.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">576.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0008370&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0008370</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001396" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001396</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001396" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001396</a>]</span><br /> -
Cholangitis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/82403002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">82403002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K83.09" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K83.09</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K83.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K83.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/576.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">576.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0008311&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0008311</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030151" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030151</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030151" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030151</a>]</span><br /> -
Hepatosiderosis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1852377&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1852377</a>]</span><br /> -
Microvesicular steatosis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1850415&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1850415</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001414" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001414</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001414" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001414</a>]</span><br /> -
Decreased complex III activity in liver tissue <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1852378&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1852378</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">
- 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> GENITOURINARY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Kidneys </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Tubulointerstitial nephritis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/428255004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">428255004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/N10-N16" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N10-N16</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/N15.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N15.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/N16" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">N16</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0041349&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0041349</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001969" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001969</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001970" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001970</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001970" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001970</a>]</span><br /> -
Renal tubulopathy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1852374&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1852374</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKIN, NAILS, & HAIR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Hair </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Brittle hair (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/25159003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">25159003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/L67.8" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">L67.8</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0263490&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0263490</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002299" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002299</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002299" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002299</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MUSCLE, SOFT TISSUES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Hypotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398151007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398151007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398152000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398152000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026827&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026827</a>, <a href="https://bioportal.bioontology.org/search?q=C1858120&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858120</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001290</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span><br /> -
Muscle weakness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/26544005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">26544005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151786&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151786</a>, <a href="https://bioportal.bioontology.org/search?q=C0030552&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0030552</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001324" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001324</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001324" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001324</a>]</span><br /> -
Ragged red fibers seen on muscle biopsy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3151935&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3151935</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003200" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003200</a>]</span><br /> -
Decreased mitochondrial complex III activity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3149083&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3149083</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011924" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011924</a>]</span><br /> -
Other mitochondrial complex enzyme activities may also be decreased <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3149084&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3149084</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> NEUROLOGIC </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Central Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Delayed psychomotor development <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 /> -
Mental retardation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/228156007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">228156007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/110359009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">110359009</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/317-319.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">317-319.99</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714756&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714756</a>, <a href="https://bioportal.bioontology.org/search?q=C0025362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span><br /> -
Mitochondrial encephalopathy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1852373&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1852373</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006789" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006789</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0006789" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0006789</a>]</span><br /> -
Hyperreflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/86854008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">86854008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151889&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151889</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001347</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001347</a>]</span><br /> -
Spasticity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/221360009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">221360009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/397790002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">397790002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026838&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026838</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001257" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001257</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001257" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001257</a>]</span><br /> -
Motor dysfunction <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/52559000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">52559000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/264552009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">264552009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0521654&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0521654</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 /> -
Abnormal EEG <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/274521009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">274521009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R94.01" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R94.01</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151611&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151611</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002353" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002353</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002353" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002353</a>]</span><br /> -
Cerebral atrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/278849000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">278849000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0235946&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0235946</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002059" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002059</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002059" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002059</a>]</span><br /> -
Cerebellar atrophy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0740279&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0740279</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001272" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001272</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001272" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001272</a>]</span><br /> -
White matter lesions may occur in the thalami, basal ganglia, and periventricular white matter (see Leigh syndrome, <a href="/entry/256000">256000</a>) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2752009&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2752009</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> METABOLIC FEATURES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Lactic acidosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91273001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91273001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E87.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E87.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0001125&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0001125</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003128" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003128</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003128" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003128</a>]</span><br /> -
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 /> -
Hypoglycemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237630007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237630007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/271327008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">271327008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/302866003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">302866003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1179458001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1179458001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E16.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E16.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/251.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">251.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020615&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020615</a>, <a href="https://bioportal.bioontology.org/search?q=C5767385&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5767385</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001943" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001943</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001943" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001943</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEMATOLOGY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Coagulation defect due to decreased liver function <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1852382&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1852382</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/64779008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">64779008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/362970003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">362970003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D68.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D68.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/286" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">286</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Increased serum lactate <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5888306&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5888306</a>, <a href="https://bioportal.bioontology.org/search?q=C1836440&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836440</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002151" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002151</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002151" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002151</a>]</span><br /> -
Abnormal liver function tests <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/166603001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">166603001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R94.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R94.5</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/794.8" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">794.8</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151766&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151766</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 /> -
Aminoaciduria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/35912001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">35912001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0238621&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0238621</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003355" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003355</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003355" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003355</a>]</span><br /> -
Decreased respiratory chain complex III activity in multiple tissues <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1852381&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1852381</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Onset in infancy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1848924&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1848924</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003593" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003593</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003593" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003593</a>]</span><br /> -
May result in early death<br />
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<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
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<div style="margin-left: 2em;">
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<span class="mim-font">
- Caused by mutation in the BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone gene (BCS1L, <a href="/entry/603647#0001">603647.0001</a>)<br />
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<h5>
Mitochondrial complex III deficiency, nuclear type
- <a href="/phenotypicSeries/PS124000">PS124000</a>
- 11 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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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<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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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />MIM number</strong>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<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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</tr>
</thead>
<tbody>
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<td>
<span class="mim-font">
<a href="/geneMap/1/575?start=-3&limit=10&highlight=575"> 1p33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/620137"> ?Mitochondrial complex III deficiency, nuclear type 11 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
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<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/620137"> 620137 </a>
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</td>
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<span class="mim-font">
<a href="/entry/613844"> UQCRH </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613844"> 613844 </a>
</span>
</td>
</tr>
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<td>
<span class="mim-font">
<a href="/geneMap/2/1014?start=-3&limit=10&highlight=1014"> 2q35 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/124000"> Mitochondrial complex III deficiency, nuclear type 1 </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/124000"> 124000 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603647"> BCS1L </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603647"> 603647 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/420?start=-3&limit=10&highlight=420"> 5q23.3-q31.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615838"> Mitochondrial complex III deficiency, nuclear type 8 </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/615838"> 615838 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615831"> LYRM7 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615831"> 615831 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/5/459?start=-3&limit=10&highlight=459"> 5q31.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615159"> Mitochondrial complex III deficiency, nuclear type 4 </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/615159"> 615159 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612080"> UQCRQ </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/612080"> 612080 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/406?start=-3&limit=10&highlight=406"> 6p21.31 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615824"> Mitochondrial complex III deficiency, nuclear type 7 </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/615824"> 615824 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614461"> UQCC2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614461"> 614461 </a>
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</td>
</tr>
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<td>
<span class="mim-font">
<a href="/geneMap/8/421?start=-3&limit=10&highlight=421"> 8q22.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615158"> Mitochondrial complex III deficiency, nuclear type 3 </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/615158"> 615158 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/191330"> UQCRB </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/191330"> 191330 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/8/629?start=-3&limit=10&highlight=629"> 8q24.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615453"> Mitochondrial complex III deficiency, nuclear type 6 </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/615453"> 615453 </a>
</span>
</td>
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<span class="mim-font">
<a href="/entry/123980"> CYC1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/123980"> 123980 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/487?start=-3&limit=10&highlight=487"> 11q12.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616111"> ?Mitochondrial complex III deficiency, nuclear type 9 </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/616111"> 616111 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616097"> UQCC3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616097"> 616097 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/16/264?start=-3&limit=10&highlight=264"> 16p12.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615160"> Mitochondrial complex III deficiency, nuclear type 5 </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/615160"> 615160 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/191329"> UQCRC2 </a>
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</td>
<td>
<span class="mim-font">
<a href="/entry/191329"> 191329 </a>
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</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/17/251?start=-3&limit=10&highlight=251"> 17p12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/615157"> Mitochondrial complex III deficiency, nuclear type 2 </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/615157"> 615157 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/613814"> TTC19 </a>
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</td>
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<span class="mim-font">
<a href="/entry/613814"> 613814 </a>
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</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/523?start=-3&limit=10&highlight=523"> 19q12 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/618775"> Mitochondrial complex III deficiency, nuclear type 10 </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/618775"> 618775 </a>
</span>
</td>
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<span class="mim-font">
<a href="/entry/191327"> UQCRFS1 </a>
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<span class="mim-font">
<a href="/entry/191327"> 191327 </a>
</span>
</td>
</tr>
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<p>A number sign (#) is used with this entry because mitochondrial complex III deficiency nuclear type 1 (MC3DN1) is caused by homozygous or compound heterozygous mutation in the nuclear-encoded BCS1L gene (<a href="/entry/603647">603647</a>) on chromosome 2q35.</p>
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<strong>Description</strong>
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<p>Autosomal recessive mitochondrial complex III deficiency is a severe multisystem disorder with onset at birth of lactic acidosis, hypotonia, hypoglycemia, failure to thrive, encephalopathy, and delayed psychomotor development. Visceral involvement, including hepatopathy and renal tubulopathy, may also occur. Many patients die in early childhood, but some may show longer survival (<a href="#2" class="mim-tip-reference" title="de Lonlay, P., Valnot, I., Barrientos, A., Gorbatyuk, M., Tzagoloff, A., Taanman, J.-W., Benayoun, E., Chretien, D., Kadhom, N., Lombes, A., Ogier de Baulny, H., Niaudet, P., Munnich, A., Rustin, P., Rotig, A. &lt;strong&gt;A mutant mitochondrial respiratory chain assembly protein causes complex III deficiency in patients with tubulopathy, encephalopathy and liver failure.&lt;/strong&gt; Nature Genet. 29: 57-60, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11528392/&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;11528392&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng706&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="11528392">de Lonlay et al., 2001</a>; <a href="#3" class="mim-tip-reference" title="De Meirleir, L., Seneca, S., Damis, E., Sepulchre, B., Hoorens, A., Gerlo, E., Garcia Silva, M. T., Hernandez, E. M., Lissens, W., Van Coster, R. &lt;strong&gt;Clinical and diagnostic characteristics of complex III deficiency due to mutations in the BCS1L gene.&lt;/strong&gt; Am. J. Med. Genet. 121A: 126-131, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12910490/&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;12910490&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.20171&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="12910490">De Meirleir et al., 2003</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11528392+12910490" 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>Genetic Heterogeneity of Mitochondrial Complex III Deficiency</em></strong></p><p>
Mitochondrial complex III deficiency can be caused by mutation in several different nuclear-encoded genes. See MC3DN2 (<a href="/entry/615157">615157</a>), caused by mutation in the TTC19 gene (<a href="/entry/613814">613814</a>) on chromosome 17p12; MC3DN3 (<a href="/entry/615158">615158</a>), caused by mutation in the UQCRB gene (<a href="/entry/191330">191330</a>) on chromosome 8q; MC3DN4 (<a href="/entry/615159">615159</a>), caused by mutation in the UQCRQ gene (<a href="/entry/612080">612080</a>) on chromosome 5q31; MC3DN5 (<a href="/entry/615160">615160</a>), caused by mutation in the UQCRC2 gene (<a href="/entry/191329">191329</a>) on chromosome 16p12; MC3DN6 (<a href="/entry/615453">615453</a>), caused by mutation in the CYC1 gene (<a href="/entry/123980">123980</a>) on chromosome 8q24; MC3DN7 (<a href="/entry/615824">615824</a>), caused by mutation in the UQCC2 gene (<a href="/entry/614461">614461</a>) on chromosome 6p21; MC3DN8 (<a href="/entry/615838">615838</a>), caused by mutation in the LYRM7 gene (<a href="/entry/615831">615831</a>) on chromosome 5q23; MC3DN9 (<a href="/entry/616111">616111</a>), caused by mutation in the UQCC3 gene (<a href="/entry/616097">616097</a>) on chromosome 11q12; and MC3DN10 (<a href="/entry/618775">618775</a>), caused by mutation in the UQCRFS1 gene (<a href="/entry/191327">191327</a>) on chromosome 19q12.</p><p>See also MTYCB (<a href="/entry/516020">516020</a>) for a discussion of a milder phenotype associated with isolated mitochondrial complex III deficiency and mutations in a mitochondrial-encoded gene.</p>
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<strong>Clinical Features</strong>
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<p><a href="#2" class="mim-tip-reference" title="de Lonlay, P., Valnot, I., Barrientos, A., Gorbatyuk, M., Tzagoloff, A., Taanman, J.-W., Benayoun, E., Chretien, D., Kadhom, N., Lombes, A., Ogier de Baulny, H., Niaudet, P., Munnich, A., Rustin, P., Rotig, A. &lt;strong&gt;A mutant mitochondrial respiratory chain assembly protein causes complex III deficiency in patients with tubulopathy, encephalopathy and liver failure.&lt;/strong&gt; Nature Genet. 29: 57-60, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11528392/&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;11528392&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng706&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="11528392">De Lonlay et al. (2001)</a> reported 6 patients from 4 unrelated Turkish families with complex III deficiency who presented with neonatal proximal tubulopathy, hepatic involvement, and encephalopathy. The first patient was a girl born to consanguineous parents after a normal pregnancy and delivery. Immediately after birth she presented feeding difficulties with vomiting and gastric hemorrhage. She developed liver failure, lactic acidosis, and tubulointerstitial nephritis, as well as severe encephalopathy with microcephaly, deafness, and blindness, and died at age 3 months. Her sister was born after an uneventful pregnancy and delivery but developed lactic acidosis immediately after birth. Subsequently, she developed severe encephalopathy and hepatic dysfunction with mild cholestasis, elevated liver enzymes, and tubulopathy. At 2 years of age, brain MRI showed atrophy and large reduction in white matter. Complex III deficiency was demonstrated in muscle from this patient and in the liver of an aborted fetus in this family. A boy, born to consanguineous parents who were unrelated to the first family, was small for gestational age and developed a de Toni-Debre-Fanconi syndrome immediately after birth. He was hypotonic with brisk tendon reflexes and had a metabolic acidosis with a plasma lactate level of 8 mmol/l. He had mildly elevated liver enzymes as well as mildly elevated CPK. Krebs cycle intermediates accumulated in his urine. Cerebral ultrasound showed scattered brainstem lesions compatible with a diagnosis of Leigh syndrome (<a href="/entry/256000">256000</a>). The patient's neurologic condition rapidly worsened and he died at 6 months of age. In another unrelated family, a girl was born to consanguineous parents after a postterm pregnancy. She was small for gestational age, and developed severe metabolic acidosis with a plasma lactate level of 22 mmol/l. Tests showed elevated liver enzyme levels, and Krebs cycle intermediates were found in her urine. She developed proximal tubulopathy, and renal ultrasound showed hyperechogenic kidneys. At 1 year of age, she had acute episodes of ventilation abnormalities, and died from central ventilatory failure at 2 years of age. Cerebral MRI showed lesions scattered from the basal ganglia to the brainstem compatible with a diagnosis of Leigh syndrome. The last patient was a boy born to nonconsanguineous parents unrelated to all other families after an uneventful pregnancy and delivery. He developed metabolic acidosis immediately after birth and presented with elevated liver enzyme levels, hypoglycemia, and urinary accumulation of Krebs cycle intermediates. He experienced acute myoglobinuria at 1 month of age. Psychomotor development was normal at 5 months of age, after which the patient was lost to follow-up. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11528392" 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="Fernandez-Vizarra, E., Bugiani, M., Goffrini, P., Carrara, F., Farina, L., Procopio, E., Donati, A., Uziel, G., Ferrero, I., Zeviani, M. &lt;strong&gt;Impaired complex III assembly associated with BCS1L gene mutations in isolated mitochondrial encephalopathy.&lt;/strong&gt; Hum. Molec. Genet. 16: 1241-1252, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17403714/&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;17403714&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddm072&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="17403714">Fernandez-Vizarra et al. (2007)</a> reported 2 unrelated girls with complex III deficiency who presented with an encephalopathic phenotype. In the first months of life, the first child, born of unrelated Italian parents, showed failure to thrive, muscle hypotonia, severe psychomotor delay, and seizures. By 1 year of age she had severe spastic quadriparesis with muscle wasting, no postural control, and persistent lactic acidosis. She died at age 4 years. The second girl, born of unrelated Moroccan parents, showed normal development until age 9 months, when she presented with acute psychomotor regression, muscle hypotonia, and failure to thrive. Symptoms progressed to spastic quadriparesis and severe mental impairment. Blood lactate was increased in both girls. Brain MRI in both patients showed cerebral atrophy and abnormal signals in the thalami, basal ganglia, and periventricular white matter. Although neither patient had other organ involvement, including heart, liver, and kidneys, both had brittle hair. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17403714" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Blazquez, A., Gil-Borlado, M. C., Moran, M., Verdu, A., Cazorla-Calleja, M. R., Martin, M. A., Arenas, J., Ugalde, C. &lt;strong&gt;Infantile mitochondrial encephalomyopathy with unusual phenotype caused by a novel BCS1L mutation in an isolated complex III-deficient patient.&lt;/strong&gt; Neuromusc. Disord. 19: 143-146, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19162478/&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;19162478&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2008.11.016&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="19162478">Blazquez et al. (2009)</a> reported a 4-year-old Spanish boy with complex III deficiency due to a homozygous BCS1L mutation. He presented at 6 months of age with psychomotor retardation, failure to thrive, hypotonia, lactic acidosis, and hepatic dysfunction. Physical examination showed unstable head support, poor eye fixation, coarse facies, and epicanthus. There was hypertrichosis of the frontal head zone and limbs, and excessive fat distribution in the upper back, neck, hands and feet, with almost no fat on the limbs. Respiratory chain activity in muscle and fibroblasts showed an isolated complex III defect (58% of normal in muscle, 93% in fibroblasts). At age 4 years, he still showed psychomotor retardation, had developed mild sensorineural hearing loss, and persistent lactic acidemia, but renal function, hair, and iron metabolism were normal. Brain MRI was normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19162478" 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="#3" class="mim-tip-reference" title="De Meirleir, L., Seneca, S., Damis, E., Sepulchre, B., Hoorens, A., Gerlo, E., Garcia Silva, M. T., Hernandez, E. M., Lissens, W., Van Coster, R. &lt;strong&gt;Clinical and diagnostic characteristics of complex III deficiency due to mutations in the BCS1L gene.&lt;/strong&gt; Am. J. Med. Genet. 121A: 126-131, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12910490/&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;12910490&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.20171&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="12910490">De Meirleir et al. (2003)</a> reported 2 Spanish sibs with fatal infantile complex III deficiency caused by compound heterozygosity for mutation in the BCS1L gene (R45C, <a href="/entry/603647#0006">603647.0006</a>; R56X, <a href="/entry/603647#0007">603647.0007</a>). Both had severe metabolic acidosis noted shortly after birth, as well as difficulty regulating blood sugar levels. Both had severe liver dysfunction and a renal tubulopathy. One died at age 3 weeks of lactic acidosis. The second infant also developed obvious neurologic involvement, with delayed myelination, axial hypotonia, and developmental delay. He died at age 3 months. Postmortem liver examination of both infants showed liver fibrosis, severe cholestasis, and hepatosiderosis with accumulation of iron in aggregates of macrophages and in Kupffer cells. Mitochondria appeared enlarged with few or no cristae and a fluffy matrix. <a href="#3" class="mim-tip-reference" title="De Meirleir, L., Seneca, S., Damis, E., Sepulchre, B., Hoorens, A., Gerlo, E., Garcia Silva, M. T., Hernandez, E. M., Lissens, W., Van Coster, R. &lt;strong&gt;Clinical and diagnostic characteristics of complex III deficiency due to mutations in the BCS1L gene.&lt;/strong&gt; Am. J. Med. Genet. 121A: 126-131, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12910490/&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;12910490&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.20171&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="12910490">De Meirleir et al. (2003)</a> suggested that the iron accumulation could be explained by the lack of incorporation of iron in the iron-sulfur cluster of complex III. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12910490" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Ramos-Arroyo, M. A., Hualde, J., Ayechu, A., De Meirleir, L., Seneca, S., Nadal, N., Briones, P. &lt;strong&gt;Clinical and biochemical spectrum of mitochondrial complex III deficiency caused by mutations in the BCS1L gene. (Letter)&lt;/strong&gt; Clin. Genet. 75: 585-587, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19508421/&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;19508421&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.2009.01160.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="19508421">Ramos-Arroyo et al. (2009)</a> reported another Spanish infant with the R45C and R56X mutations. She presented with neonatal severe hypotonia, food intolerance, and vomiting. She soon developed a proximal renal tubulopathy with glucosuria, phosphaturia, and aminoaciduria, metabolic lactic acidosis, and hepatic involvement. Bilateral cataracts were also noted. At age 4 months, she showed nystagmus, hypertonia, microcephaly, developmental delay, and failure to thrive. Her neurologic condition and metabolic acidosis worsened rapidly, and she died at 6 months of age. Biochemical studies of muscle tissue showed impaired activity of mitochondrial complex III. <a href="#7" class="mim-tip-reference" title="Ramos-Arroyo, M. A., Hualde, J., Ayechu, A., De Meirleir, L., Seneca, S., Nadal, N., Briones, P. &lt;strong&gt;Clinical and biochemical spectrum of mitochondrial complex III deficiency caused by mutations in the BCS1L gene. (Letter)&lt;/strong&gt; Clin. Genet. 75: 585-587, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19508421/&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;19508421&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.2009.01160.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="19508421">Ramos-Arroyo et al. (2009)</a> noted that this child did not have evidence of altered iron metabolism, as had been observed in the patients reported by <a href="#3" class="mim-tip-reference" title="De Meirleir, L., Seneca, S., Damis, E., Sepulchre, B., Hoorens, A., Gerlo, E., Garcia Silva, M. T., Hernandez, E. M., Lissens, W., Van Coster, R. &lt;strong&gt;Clinical and diagnostic characteristics of complex III deficiency due to mutations in the BCS1L gene.&lt;/strong&gt; Am. J. Med. Genet. 121A: 126-131, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12910490/&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;12910490&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.20171&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="12910490">De Meirleir et al. (2003)</a>, and as has been observed in patients with the allelic disorder GRACILE syndrome (<a href="/entry/603358">603358</a>). <a href="#7" class="mim-tip-reference" title="Ramos-Arroyo, M. A., Hualde, J., Ayechu, A., De Meirleir, L., Seneca, S., Nadal, N., Briones, P. &lt;strong&gt;Clinical and biochemical spectrum of mitochondrial complex III deficiency caused by mutations in the BCS1L gene. (Letter)&lt;/strong&gt; Clin. Genet. 75: 585-587, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19508421/&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;19508421&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.2009.01160.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="19508421">Ramos-Arroyo et al. (2009)</a> postulated that phenotypic variability even in individuals with the same BCS1L genotype may reflect tissue-specific expression of the mutant gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12910490+19508421" 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="pathogenesis" class="mim-anchor"></a>
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<p><a href="#6" class="mim-tip-reference" title="Moran, M., Marin-Buera, L., Gil-Borlado, M. C., Rivera, H., Blazquez, A., Seneca, S., Vazquez-Lopez, M., Arenas, J., Martin, M. A., Ugalde, C. &lt;strong&gt;Cellular pathophysiological consequences of BCS1L mutations in mitochondrial complex III enzyme deficiency.&lt;/strong&gt; Hum. Mutat. 31: 930-941, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20518024/&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;20518024&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.21294&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="20518024">Moran et al. (2010)</a> described cellular studies of 6 patients, including 2 sibs, with mitochondrial complex III deficiency due to mutations in the BCS1L gene. Four of the patients had previously been reported by <a href="#3" class="mim-tip-reference" title="De Meirleir, L., Seneca, S., Damis, E., Sepulchre, B., Hoorens, A., Gerlo, E., Garcia Silva, M. T., Hernandez, E. M., Lissens, W., Van Coster, R. &lt;strong&gt;Clinical and diagnostic characteristics of complex III deficiency due to mutations in the BCS1L gene.&lt;/strong&gt; Am. J. Med. Genet. 121A: 126-131, 2003.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12910490/&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;12910490&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.20171&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="12910490">De Meirleir et al. (2003)</a>, <a href="#1" class="mim-tip-reference" title="Blazquez, A., Gil-Borlado, M. C., Moran, M., Verdu, A., Cazorla-Calleja, M. R., Martin, M. A., Arenas, J., Ugalde, C. &lt;strong&gt;Infantile mitochondrial encephalomyopathy with unusual phenotype caused by a novel BCS1L mutation in an isolated complex III-deficient patient.&lt;/strong&gt; Neuromusc. Disord. 19: 143-146, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19162478/&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;19162478&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2008.11.016&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="19162478">Blazquez et al. (2009)</a>, and <a href="#5" class="mim-tip-reference" title="Gil-Borlado, M. C., Gonzalez-Hoyuela, M., Blazquez, A., Garcia-Silva, M. T., Gabaldon, T., Manzanares, J., Vara, J., Martin, M. A., Seneca, S., Arenas, J., Ugalde, C. &lt;strong&gt;Pathogenic mutations in the 5-prime untranslated region of BCS1L mRNA in mitochondrial complex III deficiency.&lt;/strong&gt; Mitochondrion 9: 299-305, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19389488/&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;19389488&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.mito.2009.04.001&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="19389488">Gil-Borlado et al. (2009)</a>. Two of the patients were reported for the first time: 1 with early death at age 7 months and another with a slightly attenuated phenotype who was alive at age 5 years. Cultured fibroblasts from the patients showed variable deficiency of complex III activity, which correlated with the phenotypic severity. The 2 least severely affected individuals had low-normal levels of complex III activity and expression. Other complex activities were variably affected in all patients. Fibroblasts from all patients showed defective growth in glucose medium, with greater relative growth in the less severely affected patients. Western blot analysis detected accumulation of mutant BCS1L in the cytoplasm of patients fibroblasts, suggesting impaired mitochondrial import of the mutant protein, and reduced levels of intramitochondrial fully-assembled BCS1L complexes compared to wildtype cells. The more severely affected patients also showed evidence of increased reactive oxygen species and apoptosis compared to the lesser affected patients. Mitochondrial structure abnormalities were also observed. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=19162478+19389488+20518024+12910490" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In 6 patients with complex III deficiency, <a href="#2" class="mim-tip-reference" title="de Lonlay, P., Valnot, I., Barrientos, A., Gorbatyuk, M., Tzagoloff, A., Taanman, J.-W., Benayoun, E., Chretien, D., Kadhom, N., Lombes, A., Ogier de Baulny, H., Niaudet, P., Munnich, A., Rustin, P., Rotig, A. &lt;strong&gt;A mutant mitochondrial respiratory chain assembly protein causes complex III deficiency in patients with tubulopathy, encephalopathy and liver failure.&lt;/strong&gt; Nature Genet. 29: 57-60, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11528392/&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;11528392&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng706&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="11528392">de Lonlay et al. (2001)</a> identified biallelic mutations in the BCS1L gene (<a href="/entry/603647#0001">603647.0001</a>-<a href="/entry/603647#0004">603647.0004</a>). Complementation studies in yeast confirmed the deleterious effect of the mutations in these patients. <a href="#2" class="mim-tip-reference" title="de Lonlay, P., Valnot, I., Barrientos, A., Gorbatyuk, M., Tzagoloff, A., Taanman, J.-W., Benayoun, E., Chretien, D., Kadhom, N., Lombes, A., Ogier de Baulny, H., Niaudet, P., Munnich, A., Rustin, P., Rotig, A. &lt;strong&gt;A mutant mitochondrial respiratory chain assembly protein causes complex III deficiency in patients with tubulopathy, encephalopathy and liver failure.&lt;/strong&gt; Nature Genet. 29: 57-60, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11528392/&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;11528392&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng706&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="11528392">De Lonlay et al. (2001)</a> concluded that mutation of BCS1L seems to be a frequent cause of complex III deficiency, as one-third of their Turkish patients with complex III deficiency had BCS1L mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11528392" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 unrelated girls with complex III deficiency manifest as encephalopathy, <a href="#4" class="mim-tip-reference" title="Fernandez-Vizarra, E., Bugiani, M., Goffrini, P., Carrara, F., Farina, L., Procopio, E., Donati, A., Uziel, G., Ferrero, I., Zeviani, M. &lt;strong&gt;Impaired complex III assembly associated with BCS1L gene mutations in isolated mitochondrial encephalopathy.&lt;/strong&gt; Hum. Molec. Genet. 16: 1241-1252, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17403714/&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;17403714&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/hmg/ddm072&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="17403714">Fernandez-Vizarra et al. (2007)</a> identified compound heterozygous mutations in the BCS1L gene (see, e.g., R184C; <a href="/entry/603647#0009">603647.0009</a> and R183C; <a href="/entry/603647#0012">603647.0012</a>). Studies in yeast showed that the mutations significantly reduced mitochondrial cytochrome content and respiratory activity, as well resulted in decreased levels of fully assembled complex III. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17403714" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Blazquez, A., Gil-Borlado, M. C., Moran, M., Verdu, A., Cazorla-Calleja, M. R., Martin, M. A., Arenas, J., Ugalde, C. &lt;strong&gt;Infantile mitochondrial encephalomyopathy with unusual phenotype caused by a novel BCS1L mutation in an isolated complex III-deficient patient.&lt;/strong&gt; Neuromusc. Disord. 19: 143-146, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19162478/&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;19162478&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.nmd.2008.11.016&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="19162478">Blazquez et al. (2009)</a> reported a 4-year-old Spanish boy with complex III deficiency caused by a homozygous mutation in the BCS1L gene (T50A; <a href="/entry/603647#0011">603647.0011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19162478" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>REFERENCES</strong>
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<a id="Blazquez2009" class="mim-anchor"></a>
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Blazquez, A., Gil-Borlado, M. C., Moran, M., Verdu, A., Cazorla-Calleja, M. R., Martin, M. A., Arenas, J., Ugalde, C.
<strong>Infantile mitochondrial encephalomyopathy with unusual phenotype caused by a novel BCS1L mutation in an isolated complex III-deficient patient.</strong>
Neuromusc. Disord. 19: 143-146, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19162478/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19162478</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19162478" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.nmd.2008.11.016" target="_blank">Full Text</a>]
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<a id="de Lonlay2001" class="mim-anchor"></a>
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de Lonlay, P., Valnot, I., Barrientos, A., Gorbatyuk, M., Tzagoloff, A., Taanman, J.-W., Benayoun, E., Chretien, D., Kadhom, N., Lombes, A., Ogier de Baulny, H., Niaudet, P., Munnich, A., Rustin, P., Rotig, A.
<strong>A mutant mitochondrial respiratory chain assembly protein causes complex III deficiency in patients with tubulopathy, encephalopathy and liver failure.</strong>
Nature Genet. 29: 57-60, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11528392/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11528392</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11528392" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/ng706" target="_blank">Full Text</a>]
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<a id="De Meirleir2003" class="mim-anchor"></a>
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De Meirleir, L., Seneca, S., Damis, E., Sepulchre, B., Hoorens, A., Gerlo, E., Garcia Silva, M. T., Hernandez, E. M., Lissens, W., Van Coster, R.
<strong>Clinical and diagnostic characteristics of complex III deficiency due to mutations in the BCS1L gene.</strong>
Am. J. Med. Genet. 121A: 126-131, 2003.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12910490/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12910490</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12910490" 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.20171" target="_blank">Full Text</a>]
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<a id="Fernandez-Vizarra2007" class="mim-anchor"></a>
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Fernandez-Vizarra, E., Bugiani, M., Goffrini, P., Carrara, F., Farina, L., Procopio, E., Donati, A., Uziel, G., Ferrero, I., Zeviani, M.
<strong>Impaired complex III assembly associated with BCS1L gene mutations in isolated mitochondrial encephalopathy.</strong>
Hum. Molec. Genet. 16: 1241-1252, 2007.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17403714/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17403714</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17403714" 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/ddm072" target="_blank">Full Text</a>]
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<a id="Gil-Borlado2009" class="mim-anchor"></a>
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Gil-Borlado, M. C., Gonzalez-Hoyuela, M., Blazquez, A., Garcia-Silva, M. T., Gabaldon, T., Manzanares, J., Vara, J., Martin, M. A., Seneca, S., Arenas, J., Ugalde, C.
<strong>Pathogenic mutations in the 5-prime untranslated region of BCS1L mRNA in mitochondrial complex III deficiency.</strong>
Mitochondrion 9: 299-305, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19389488/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19389488</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19389488" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.mito.2009.04.001" target="_blank">Full Text</a>]
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<a id="Moran2010" class="mim-anchor"></a>
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Moran, M., Marin-Buera, L., Gil-Borlado, M. C., Rivera, H., Blazquez, A., Seneca, S., Vazquez-Lopez, M., Arenas, J., Martin, M. A., Ugalde, C.
<strong>Cellular pathophysiological consequences of BCS1L mutations in mitochondrial complex III enzyme deficiency.</strong>
Hum. Mutat. 31: 930-941, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20518024/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20518024</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20518024" 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.21294" target="_blank">Full Text</a>]
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<a id="Ramos-Arroyo2009" class="mim-anchor"></a>
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Ramos-Arroyo, M. A., Hualde, J., Ayechu, A., De Meirleir, L., Seneca, S., Nadal, N., Briones, P.
<strong>Clinical and biochemical spectrum of mitochondrial complex III deficiency caused by mutations in the BCS1L gene. (Letter)</strong>
Clin. Genet. 75: 585-587, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19508421/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19508421</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19508421" 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.1399-0004.2009.01160.x" target="_blank">Full Text</a>]
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Cassandra L. Kniffin - updated : 4/8/2013
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Cassandra L. Kniffin - updated : 3/21/2011<br>Cassandra L. Kniffin - updated : 11/29/2010<br>Cassandra L. Kniffin - updated : 6/1/2010<br>Cassandra L. Kniffin - updated : 3/9/2010<br>Cassandra L. Kniffin - updated : 11/4/2009<br>Cassandra L. Kniffin - updated : 10/5/2005
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Creation Date:
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Victor A. McKusick : 6/4/1986
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carol : 02/17/2020
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ckniffin : 02/13/2020<br>carol : 06/21/2016<br>carol : 12/1/2014<br>ckniffin : 12/1/2014<br>alopez : 6/11/2014<br>ckniffin : 6/5/2014<br>carol : 6/3/2014<br>ckniffin : 6/2/2014<br>carol : 10/2/2013<br>ckniffin : 10/2/2013<br>carol : 4/8/2013<br>ckniffin : 4/8/2013<br>carol : 3/22/2011<br>ckniffin : 3/21/2011<br>wwang : 11/30/2010<br>ckniffin : 11/29/2010<br>ckniffin : 11/24/2010<br>wwang : 6/4/2010<br>ckniffin : 6/1/2010<br>wwang : 3/24/2010<br>ckniffin : 3/9/2010<br>wwang : 11/18/2009<br>ckniffin : 11/4/2009<br>wwang : 6/3/2008<br>ckniffin : 5/27/2008<br>wwang : 10/12/2005<br>ckniffin : 10/5/2005<br>carol : 9/21/2005<br>ckniffin : 8/29/2005<br>carol : 6/30/2004<br>carol : 8/19/1998<br>mimadm : 6/25/1994<br>supermim : 3/16/1992<br>supermim : 3/20/1990<br>supermim : 12/31/1989<br>carol : 12/9/1989<br>ddp : 10/26/1989
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<strong>#</strong> 124000
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MITOCHONDRIAL COMPLEX III DEFICIENCY, NUCLEAR TYPE 1; MC3DN1
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<strong>ORPHA:</strong> 1460, 254902; &nbsp;
<strong>DO:</strong> 0080111; &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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2q35
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Mitochondrial complex III deficiency, nuclear type 1
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124000
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Autosomal recessive
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3
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BCS1L
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603647
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because mitochondrial complex III deficiency nuclear type 1 (MC3DN1) is caused by homozygous or compound heterozygous mutation in the nuclear-encoded BCS1L gene (603647) on chromosome 2q35.</p>
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<strong>Description</strong>
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<p>Autosomal recessive mitochondrial complex III deficiency is a severe multisystem disorder with onset at birth of lactic acidosis, hypotonia, hypoglycemia, failure to thrive, encephalopathy, and delayed psychomotor development. Visceral involvement, including hepatopathy and renal tubulopathy, may also occur. Many patients die in early childhood, but some may show longer survival (de Lonlay et al., 2001; De Meirleir et al., 2003). </p><p><strong><em>Genetic Heterogeneity of Mitochondrial Complex III Deficiency</em></strong></p><p>
Mitochondrial complex III deficiency can be caused by mutation in several different nuclear-encoded genes. See MC3DN2 (615157), caused by mutation in the TTC19 gene (613814) on chromosome 17p12; MC3DN3 (615158), caused by mutation in the UQCRB gene (191330) on chromosome 8q; MC3DN4 (615159), caused by mutation in the UQCRQ gene (612080) on chromosome 5q31; MC3DN5 (615160), caused by mutation in the UQCRC2 gene (191329) on chromosome 16p12; MC3DN6 (615453), caused by mutation in the CYC1 gene (123980) on chromosome 8q24; MC3DN7 (615824), caused by mutation in the UQCC2 gene (614461) on chromosome 6p21; MC3DN8 (615838), caused by mutation in the LYRM7 gene (615831) on chromosome 5q23; MC3DN9 (616111), caused by mutation in the UQCC3 gene (616097) on chromosome 11q12; and MC3DN10 (618775), caused by mutation in the UQCRFS1 gene (191327) on chromosome 19q12.</p><p>See also MTYCB (516020) for a discussion of a milder phenotype associated with isolated mitochondrial complex III deficiency and mutations in a mitochondrial-encoded gene.</p>
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<strong>Clinical Features</strong>
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<p>De Lonlay et al. (2001) reported 6 patients from 4 unrelated Turkish families with complex III deficiency who presented with neonatal proximal tubulopathy, hepatic involvement, and encephalopathy. The first patient was a girl born to consanguineous parents after a normal pregnancy and delivery. Immediately after birth she presented feeding difficulties with vomiting and gastric hemorrhage. She developed liver failure, lactic acidosis, and tubulointerstitial nephritis, as well as severe encephalopathy with microcephaly, deafness, and blindness, and died at age 3 months. Her sister was born after an uneventful pregnancy and delivery but developed lactic acidosis immediately after birth. Subsequently, she developed severe encephalopathy and hepatic dysfunction with mild cholestasis, elevated liver enzymes, and tubulopathy. At 2 years of age, brain MRI showed atrophy and large reduction in white matter. Complex III deficiency was demonstrated in muscle from this patient and in the liver of an aborted fetus in this family. A boy, born to consanguineous parents who were unrelated to the first family, was small for gestational age and developed a de Toni-Debre-Fanconi syndrome immediately after birth. He was hypotonic with brisk tendon reflexes and had a metabolic acidosis with a plasma lactate level of 8 mmol/l. He had mildly elevated liver enzymes as well as mildly elevated CPK. Krebs cycle intermediates accumulated in his urine. Cerebral ultrasound showed scattered brainstem lesions compatible with a diagnosis of Leigh syndrome (256000). The patient's neurologic condition rapidly worsened and he died at 6 months of age. In another unrelated family, a girl was born to consanguineous parents after a postterm pregnancy. She was small for gestational age, and developed severe metabolic acidosis with a plasma lactate level of 22 mmol/l. Tests showed elevated liver enzyme levels, and Krebs cycle intermediates were found in her urine. She developed proximal tubulopathy, and renal ultrasound showed hyperechogenic kidneys. At 1 year of age, she had acute episodes of ventilation abnormalities, and died from central ventilatory failure at 2 years of age. Cerebral MRI showed lesions scattered from the basal ganglia to the brainstem compatible with a diagnosis of Leigh syndrome. The last patient was a boy born to nonconsanguineous parents unrelated to all other families after an uneventful pregnancy and delivery. He developed metabolic acidosis immediately after birth and presented with elevated liver enzyme levels, hypoglycemia, and urinary accumulation of Krebs cycle intermediates. He experienced acute myoglobinuria at 1 month of age. Psychomotor development was normal at 5 months of age, after which the patient was lost to follow-up. </p><p>Fernandez-Vizarra et al. (2007) reported 2 unrelated girls with complex III deficiency who presented with an encephalopathic phenotype. In the first months of life, the first child, born of unrelated Italian parents, showed failure to thrive, muscle hypotonia, severe psychomotor delay, and seizures. By 1 year of age she had severe spastic quadriparesis with muscle wasting, no postural control, and persistent lactic acidosis. She died at age 4 years. The second girl, born of unrelated Moroccan parents, showed normal development until age 9 months, when she presented with acute psychomotor regression, muscle hypotonia, and failure to thrive. Symptoms progressed to spastic quadriparesis and severe mental impairment. Blood lactate was increased in both girls. Brain MRI in both patients showed cerebral atrophy and abnormal signals in the thalami, basal ganglia, and periventricular white matter. Although neither patient had other organ involvement, including heart, liver, and kidneys, both had brittle hair. </p><p>Blazquez et al. (2009) reported a 4-year-old Spanish boy with complex III deficiency due to a homozygous BCS1L mutation. He presented at 6 months of age with psychomotor retardation, failure to thrive, hypotonia, lactic acidosis, and hepatic dysfunction. Physical examination showed unstable head support, poor eye fixation, coarse facies, and epicanthus. There was hypertrichosis of the frontal head zone and limbs, and excessive fat distribution in the upper back, neck, hands and feet, with almost no fat on the limbs. Respiratory chain activity in muscle and fibroblasts showed an isolated complex III defect (58% of normal in muscle, 93% in fibroblasts). At age 4 years, he still showed psychomotor retardation, had developed mild sensorineural hearing loss, and persistent lactic acidemia, but renal function, hair, and iron metabolism were normal. Brain MRI was normal. </p><p><strong><em>Clinical Variability</em></strong></p><p>
De Meirleir et al. (2003) reported 2 Spanish sibs with fatal infantile complex III deficiency caused by compound heterozygosity for mutation in the BCS1L gene (R45C, 603647.0006; R56X, 603647.0007). Both had severe metabolic acidosis noted shortly after birth, as well as difficulty regulating blood sugar levels. Both had severe liver dysfunction and a renal tubulopathy. One died at age 3 weeks of lactic acidosis. The second infant also developed obvious neurologic involvement, with delayed myelination, axial hypotonia, and developmental delay. He died at age 3 months. Postmortem liver examination of both infants showed liver fibrosis, severe cholestasis, and hepatosiderosis with accumulation of iron in aggregates of macrophages and in Kupffer cells. Mitochondria appeared enlarged with few or no cristae and a fluffy matrix. De Meirleir et al. (2003) suggested that the iron accumulation could be explained by the lack of incorporation of iron in the iron-sulfur cluster of complex III. </p><p>Ramos-Arroyo et al. (2009) reported another Spanish infant with the R45C and R56X mutations. She presented with neonatal severe hypotonia, food intolerance, and vomiting. She soon developed a proximal renal tubulopathy with glucosuria, phosphaturia, and aminoaciduria, metabolic lactic acidosis, and hepatic involvement. Bilateral cataracts were also noted. At age 4 months, she showed nystagmus, hypertonia, microcephaly, developmental delay, and failure to thrive. Her neurologic condition and metabolic acidosis worsened rapidly, and she died at 6 months of age. Biochemical studies of muscle tissue showed impaired activity of mitochondrial complex III. Ramos-Arroyo et al. (2009) noted that this child did not have evidence of altered iron metabolism, as had been observed in the patients reported by De Meirleir et al. (2003), and as has been observed in patients with the allelic disorder GRACILE syndrome (603358). Ramos-Arroyo et al. (2009) postulated that phenotypic variability even in individuals with the same BCS1L genotype may reflect tissue-specific expression of the mutant gene. </p>
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<strong>Pathogenesis</strong>
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<p>Moran et al. (2010) described cellular studies of 6 patients, including 2 sibs, with mitochondrial complex III deficiency due to mutations in the BCS1L gene. Four of the patients had previously been reported by De Meirleir et al. (2003), Blazquez et al. (2009), and Gil-Borlado et al. (2009). Two of the patients were reported for the first time: 1 with early death at age 7 months and another with a slightly attenuated phenotype who was alive at age 5 years. Cultured fibroblasts from the patients showed variable deficiency of complex III activity, which correlated with the phenotypic severity. The 2 least severely affected individuals had low-normal levels of complex III activity and expression. Other complex activities were variably affected in all patients. Fibroblasts from all patients showed defective growth in glucose medium, with greater relative growth in the less severely affected patients. Western blot analysis detected accumulation of mutant BCS1L in the cytoplasm of patients fibroblasts, suggesting impaired mitochondrial import of the mutant protein, and reduced levels of intramitochondrial fully-assembled BCS1L complexes compared to wildtype cells. The more severely affected patients also showed evidence of increased reactive oxygen species and apoptosis compared to the lesser affected patients. Mitochondrial structure abnormalities were also observed. </p>
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<strong>Molecular Genetics</strong>
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<p>In 6 patients with complex III deficiency, de Lonlay et al. (2001) identified biallelic mutations in the BCS1L gene (603647.0001-603647.0004). Complementation studies in yeast confirmed the deleterious effect of the mutations in these patients. De Lonlay et al. (2001) concluded that mutation of BCS1L seems to be a frequent cause of complex III deficiency, as one-third of their Turkish patients with complex III deficiency had BCS1L mutations. </p><p>In 2 unrelated girls with complex III deficiency manifest as encephalopathy, Fernandez-Vizarra et al. (2007) identified compound heterozygous mutations in the BCS1L gene (see, e.g., R184C; 603647.0009 and R183C; 603647.0012). Studies in yeast showed that the mutations significantly reduced mitochondrial cytochrome content and respiratory activity, as well resulted in decreased levels of fully assembled complex III. </p><p>Blazquez et al. (2009) reported a 4-year-old Spanish boy with complex III deficiency caused by a homozygous mutation in the BCS1L gene (T50A; 603647.0011). </p>
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<strong>REFERENCES</strong>
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<p class="mim-text-font">
Blazquez, A., Gil-Borlado, M. C., Moran, M., Verdu, A., Cazorla-Calleja, M. R., Martin, M. A., Arenas, J., Ugalde, C.
<strong>Infantile mitochondrial encephalomyopathy with unusual phenotype caused by a novel BCS1L mutation in an isolated complex III-deficient patient.</strong>
Neuromusc. Disord. 19: 143-146, 2009.
[PubMed: 19162478]
[Full Text: https://doi.org/10.1016/j.nmd.2008.11.016]
</p>
</li>
<li>
<p class="mim-text-font">
de Lonlay, P., Valnot, I., Barrientos, A., Gorbatyuk, M., Tzagoloff, A., Taanman, J.-W., Benayoun, E., Chretien, D., Kadhom, N., Lombes, A., Ogier de Baulny, H., Niaudet, P., Munnich, A., Rustin, P., Rotig, A.
<strong>A mutant mitochondrial respiratory chain assembly protein causes complex III deficiency in patients with tubulopathy, encephalopathy and liver failure.</strong>
Nature Genet. 29: 57-60, 2001.
[PubMed: 11528392]
[Full Text: https://doi.org/10.1038/ng706]
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<li>
<p class="mim-text-font">
De Meirleir, L., Seneca, S., Damis, E., Sepulchre, B., Hoorens, A., Gerlo, E., Garcia Silva, M. T., Hernandez, E. M., Lissens, W., Van Coster, R.
<strong>Clinical and diagnostic characteristics of complex III deficiency due to mutations in the BCS1L gene.</strong>
Am. J. Med. Genet. 121A: 126-131, 2003.
[PubMed: 12910490]
[Full Text: https://doi.org/10.1002/ajmg.a.20171]
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</li>
<li>
<p class="mim-text-font">
Fernandez-Vizarra, E., Bugiani, M., Goffrini, P., Carrara, F., Farina, L., Procopio, E., Donati, A., Uziel, G., Ferrero, I., Zeviani, M.
<strong>Impaired complex III assembly associated with BCS1L gene mutations in isolated mitochondrial encephalopathy.</strong>
Hum. Molec. Genet. 16: 1241-1252, 2007.
[PubMed: 17403714]
[Full Text: https://doi.org/10.1093/hmg/ddm072]
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<li>
<p class="mim-text-font">
Gil-Borlado, M. C., Gonzalez-Hoyuela, M., Blazquez, A., Garcia-Silva, M. T., Gabaldon, T., Manzanares, J., Vara, J., Martin, M. A., Seneca, S., Arenas, J., Ugalde, C.
<strong>Pathogenic mutations in the 5-prime untranslated region of BCS1L mRNA in mitochondrial complex III deficiency.</strong>
Mitochondrion 9: 299-305, 2009.
[PubMed: 19389488]
[Full Text: https://doi.org/10.1016/j.mito.2009.04.001]
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<li>
<p class="mim-text-font">
Moran, M., Marin-Buera, L., Gil-Borlado, M. C., Rivera, H., Blazquez, A., Seneca, S., Vazquez-Lopez, M., Arenas, J., Martin, M. A., Ugalde, C.
<strong>Cellular pathophysiological consequences of BCS1L mutations in mitochondrial complex III enzyme deficiency.</strong>
Hum. Mutat. 31: 930-941, 2010.
[PubMed: 20518024]
[Full Text: https://doi.org/10.1002/humu.21294]
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</li>
<li>
<p class="mim-text-font">
Ramos-Arroyo, M. A., Hualde, J., Ayechu, A., De Meirleir, L., Seneca, S., Nadal, N., Briones, P.
<strong>Clinical and biochemical spectrum of mitochondrial complex III deficiency caused by mutations in the BCS1L gene. (Letter)</strong>
Clin. Genet. 75: 585-587, 2009.
[PubMed: 19508421]
[Full Text: https://doi.org/10.1111/j.1399-0004.2009.01160.x]
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