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Entry
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- #251880 - MITOCHONDRIAL DNA DEPLETION SYNDROME 3 (HEPATOCEREBRAL TYPE); MTDPS3
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- OMIM
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<p>
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<span class="h4">#251880</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<li role="presentation">
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<a href="/clinicalSynopsis/251880"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS603041"> <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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<a href="#inheritance">Inheritance</a>
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<a href="#mapping">Mapping</a>
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<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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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div style="display: table-cell;">External Links</div>
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</h4>
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<div style="display: table-row">
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<div style="display: table-cell;">Clinical Resources</div>
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<div class="panel-body small mim-panel-body">
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<div><a href="https://clinicaltrials.gov/search?cond=MITOCHONDRIAL DNA DEPLETION SYNDROME 3 (HEPATOCEREBRAL TYPE)" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=20419&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="#mimGeneReviewsFold" id="mimGeneReviewsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling."><span id="mimGeneReviewsToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Gene Reviews</div>
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<div id="mimGeneReviewsFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.ncbi.nlm.nih.gov/books/NBK487393/" title="Mitochondrial DNA Maintenance Defects Overview" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Mitochondrial DNA Maintena…</a></div><div style="margin-left: 0.5em;"><a href="https://www.ncbi.nlm.nih.gov/books/NBK7040/" title="Deoxyguanosine Kinase Deficiency" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Deoxyguanosine Kinase Defi…</a></div>
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</div>
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<div><a href="https://www.diseaseinfosearch.org/x/8901" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://medlineplus.gov/genetics/condition/deoxyguanosine-kinase-deficiency" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=251880[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=279934" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</a>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/disease/DOID:0080121" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="http://www.informatics.jax.org/disease/251880" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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<a id="title" class="mim-anchor"></a>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 783734000<br />
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<strong>ORPHA:</strong> 279934<br />
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<strong>DO:</strong> 0080121<br />
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">ICD+</a>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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251880
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</span>
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</span>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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MITOCHONDRIAL DNA DEPLETION SYNDROME 3 (HEPATOCEREBRAL TYPE); MTDPS3
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</h3>
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<div>
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<br />
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<a id="phenotypeMap" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
|
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<strong>Phenotype-Gene Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/2/371?start=-3&limit=10&highlight=371">
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2p13.1
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</a>
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</span>
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</td>
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<td>
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<span class="mim-font">
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Mitochondrial DNA depletion syndrome 3 (hepatocerebral type)
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/251880"> 251880 </a>
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</span>
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</td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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<span class="mim-font">
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DGUOK
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</span>
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</td>
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<td>
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<span class="mim-font">
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<a href="/entry/601465"> 601465 </a>
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</span>
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</td>
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</tbody>
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</table>
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<div>
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<div class="btn-group ">
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<a href="/clinicalSynopsis/251880" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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</div>
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<div class="btn-group">
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<a href="/phenotypicSeries/PS603041" class="btn btn-info" role="button"> Phenotypic Series </a>
|
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<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
|
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<span class="caret"></span>
|
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<span class="sr-only">Toggle Dropdown</span>
|
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</button>
|
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</div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
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<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/251880" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
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<li><a href="/graph/radial/251880" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
|
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</div>
|
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<div>
|
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<p />
|
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</div>
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
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<div class="small" style="margin: 5px">
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<div>
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<div>
|
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<span class="h5 mim-font">
|
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<strong> INHERITANCE </strong>
|
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</span>
|
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</div>
|
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<div style="margin-left: 2em;">
|
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<div>
|
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<span class="mim-font">
|
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|
|
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
|
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<div>
|
|
<span class="h5 mim-font">
|
|
<strong> GROWTH </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
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|
|
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|
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<div>
|
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<div>
|
|
<span class="h5 mim-font">
|
|
<em> Other </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Poor growth <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837385&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837385</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001510</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001510</a>]</span><br /> -
|
|
Failure to thrive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/432788009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">432788009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/54840006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">54840006</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0015544&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015544</a>, <a href="https://bioportal.bioontology.org/search?q=C2315100&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2315100</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Head </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Microcephaly (less common) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1148757008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1148757008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q02" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q02</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/742.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">742.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551563&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551563</a>, <a href="https://bioportal.bioontology.org/search?q=C0025958&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025958</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Microcephaly-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Eyes </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Nystagmus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/563001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">563001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/379.50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">379.50</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0028738&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0028738</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span><br /> -
|
|
Disconjugate eye movements <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1845274&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1845274</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000549" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000549</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000549" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000549</a>]</span><br /> -
|
|
Optic dysplasia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855042&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855042</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> External Features </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Ascites <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/389026000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">389026000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R18" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R18</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R18.8" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R18.8</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0003962&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0003962</a>, <a href="https://bioportal.bioontology.org/search?q=C5441966&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5441966</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001541" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001541</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0030995" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030995</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001541" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001541</a>]</span><br /> -
|
|
Portal hypertension <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/34742003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">34742003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K76.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K76.6</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/572.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">572.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020541&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020541</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001409" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001409</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001409" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001409</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Liver </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Hepatomegaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/80515008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">80515008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0019209&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0019209</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002240" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002240</a>]</span><br /> -
|
|
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 /> -
|
|
Liver tissue shows 80 to 99% depletion of mitochondrial DNA (mtDNA) with decreased activities of mitochondrial-encoded respiratory chain complexes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2673386&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2673386</a>]</span><br /> -
|
|
Biopsy shows micronodular cirrhosis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855037&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855037</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 /> -
|
|
Steatosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/442191002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">442191002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1187537008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1187537008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/197321007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">197321007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/29185008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">29185008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2711227&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2711227</a>, <a href="https://bioportal.bioontology.org/search?q=C0152254&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0152254</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001397" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001397</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001397" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001397</a>]</span><br /> -
|
|
Jaundice <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/18165001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">18165001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R17" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R17</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2203646&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2203646</a>, <a href="https://bioportal.bioontology.org/search?q=C0022346&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022346</a>, <a href="https://bioportal.bioontology.org/search?q=C2010848&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2010848</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000952" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000952</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000952" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000952</a>]</span><br /> -
|
|
Hepatocellular loss <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855038&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855038</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001404" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001404</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001404" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001404</a>]</span><br /> -
|
|
Hepatocellular necrosis <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855038&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855038</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001404" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001404</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001404" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001404</a>]</span><br /> -
|
|
Periportal fibrosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/870517000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">870517000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1849766&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1849766</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001405" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001405</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001405" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001405</a>]</span><br /> -
|
|
Pseudoacinar formation <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855039&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855039</a>]</span><br /> -
|
|
Electron microscopy shows increased and abnormal mitochondria <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855040&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855040</a>]</span><br /> -
|
|
Hepatic failure <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/59927004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">59927004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K72.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K72.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0085605&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085605</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001399" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001399</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001399" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001399</a>]</span><br />
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</span>
|
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
|
|
<em> Spleen </em>
|
|
</span>
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</div>
|
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<div style="margin-left: 2em;">
|
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<span class="mim-font">
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|
- Splenomegaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16294009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16294009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R16.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R16.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/789.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">789.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038002&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038002</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001744" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001744</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001744" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001744</a>]</span><br />
|
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</span>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
|
|
<em> Gastrointestinal </em>
|
|
</span>
|
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</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
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|
|
- 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 /> -
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|
Vomiting <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422400008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422400008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/300359004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">300359004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249497008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249497008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R11.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R11.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R11.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R11.10</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042963&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042963</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002013" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002013</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002013" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002013</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
|
|
<strong> SKIN, NAILS, & HAIR </strong>
|
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</span>
|
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</div>
|
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<div style="margin-left: 2em;">
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<div>
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<div>
|
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<span class="h5 mim-font">
|
|
<em> Skin </em>
|
|
</span>
|
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</div>
|
|
<div style="margin-left: 2em;">
|
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<span class="mim-font">
|
|
|
|
- Jaundice <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/18165001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">18165001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R17" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R17</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2203646&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2203646</a>, <a href="https://bioportal.bioontology.org/search?q=C0022346&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022346</a>, <a href="https://bioportal.bioontology.org/search?q=C2010848&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2010848</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000952" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000952</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000952" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000952</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> NEUROLOGIC </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
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<em> Central Nervous System </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Encephalopathy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/81308009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">81308009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G93.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G93.40</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/348.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">348.30</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/348.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">348.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0085584&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085584</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001298" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001298</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001298" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001298</a>]</span><br /> -
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Nystagmus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/563001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">563001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/379.50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">379.50</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0028738&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0028738</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span><br /> -
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Hypotonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398151007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398151007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398152000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398152000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026827&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026827</a>, <a href="https://bioportal.bioontology.org/search?q=C1858120&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1858120</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001290" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001290</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001252</a>]</span><br /> -
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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 /> -
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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 /> -
|
|
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 />
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</span>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
|
|
<em> Peripheral Nervous System </em>
|
|
</span>
|
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</div>
|
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<div style="margin-left: 2em;">
|
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<span class="mim-font">
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|
|
- Peripheral neuropathy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/42658009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">42658009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/302226006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">302226006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G64" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G64</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/350-359.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">350-359.99</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4721453&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4721453</a>, <a href="https://bioportal.bioontology.org/search?q=C0031117&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0031117</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009830" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009830</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0000759" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000759</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001271" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001271</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0009830" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0009830</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
|
|
<strong> METABOLIC FEATURES </strong>
|
|
</span>
|
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</div>
|
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<div style="margin-left: 2em;">
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<div>
|
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<span class="mim-font">
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|
- 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 /> -
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Hypothermia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/386689009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">386689009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/T68" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">T68</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/991.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">991.6</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/99.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">99.81</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0413252&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0413252</a>, <a href="https://bioportal.bioontology.org/search?q=C0020673&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020673</a>, <a href="https://bioportal.bioontology.org/search?q=C0020672&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020672</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002045" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002045</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002045" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002045</a>]</span><br /> -
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|
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 />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
|
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<strong> HEMATOLOGY </strong>
|
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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|
- Coagulopathy due to hepatic failure <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855043&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855043</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/64779008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">64779008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/362970003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">362970003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D68.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D68.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/286" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">286</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003256" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003256</a>]</span><br /> -
|
|
Thrombocytopenia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/415116008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">415116008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/302215000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">302215000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D69.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D69.6</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/287.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">287.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0392386&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0392386</a>, <a href="https://bioportal.bioontology.org/search?q=C0040034&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0040034</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001873" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001873</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001873" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001873</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
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|
|
|
</div>
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> LABORATORY ABNORMALITIES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Hyperbilirubinemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/14783006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">14783006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/26165005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">26165005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020433&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020433</a>, <a href="https://bioportal.bioontology.org/search?q=C0311468&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0311468</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002904" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002904</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002904" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002904</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 /> -
|
|
Hypoalbuminemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/119247004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">119247004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1153477009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1153477009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3665623&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3665623</a>, <a href="https://bioportal.bioontology.org/search?q=C0239981&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239981</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003073" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003073</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003073" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003073</a>]</span><br /> -
|
|
Generalized aminoaciduria <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1847868&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1847868</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002909" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002909</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002909" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002909</a>]</span><br />
|
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|
|
</span>
|
|
</div>
|
|
|
|
</div>
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|
|
|
</div>
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|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Onset as neonate<br /> -
|
|
Hepatic failure develops in first months of life<br /> -
|
|
Most patients die of hepatic failure by 9 months of age<br />
|
|
|
|
</span>
|
|
</div>
|
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|
|
</div>
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|
|
</div>
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|
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|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Caused by mutation in the nuclear-encoded mitochondrial deoxyguanosine kinase gene (DGUOK, <a href="/entry/601465#0001">601465.0001</a>).<br />
|
|
|
|
</span>
|
|
</div>
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|
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</div>
|
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|
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</div>
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|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
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|
|
|
|
|
|
|
|
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small">
|
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|
|
|
|
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|
|
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|
|
<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Mitochondrial DNA depletion syndrome
|
|
- <a href="/phenotypicSeries/PS603041">PS603041</a>
|
|
- 25 Entries
|
|
</h5>
|
|
</div>
|
|
</div>
|
|
|
|
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
|
<table class="table table-bordered table-condensed table-hover mim-table-padding">
|
|
<thead>
|
|
<tr>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Location</strong>
|
|
</th>
|
|
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
|
<strong>Phenotype</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Inheritance</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />mapping key</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />MIM number</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/1772?start=-3&limit=10&highlight=1772"> 1q42.13 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/621071"> Mitochondrial DNA depletion syndrome 21 </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/621071"> 621071 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/139270"> GUK1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/139270"> 139270 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/2/131?start=-3&limit=10&highlight=131"> 2p23.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/256810"> Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) </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/256810"> 256810 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/137960"> MPV17 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/137960"> 137960 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/2/371?start=-3&limit=10&highlight=371"> 2p13.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/251880"> Mitochondrial DNA depletion syndrome 3 (hepatocerebral type) </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/251880"> 251880 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601465"> DGUOK </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/601465"> 601465 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/2/413?start=-3&limit=10&highlight=413"> 2p11.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/245400"> Mitochondrial DNA depletion syndrome 9 (encephalomyopathic type with methylmalonic aciduria) </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/245400"> 245400 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611224"> SUCLG1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/611224"> 611224 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/3/975?start=-3&limit=10&highlight=975"> 3q29 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/616896"> ?Mitochondrial DNA depletion syndrome 14 (encephalocardiomyopathic type) </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/616896"> 616896 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605290"> OPA1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605290"> 605290 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/4/714?start=-3&limit=10&highlight=714"> 4q35.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/617184"> Mitochondrial DNA depletion syndrome 12A (cardiomyopathic type) AD </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal dominant">AD</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/617184"> 617184 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/103220"> SLC25A4 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/103220"> 103220 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/4/714?start=-3&limit=10&highlight=714"> 4q35.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615418"> Mitochondrial DNA depletion syndrome 12B (cardiomyopathic type) AR </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/615418"> 615418 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/103220"> SLC25A4 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/103220"> 103220 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/6/722?start=-3&limit=10&highlight=722"> 6q16.1-q16.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/615471"> Mitochondrial DNA depletion syndrome 13 (encephalomyopathic type) </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/615471"> 615471 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605654"> FBXL4 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605654"> 605654 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/7/21?start=-3&limit=10&highlight=21"> 7p22.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/618567"> Mitochondrial DNA depletion syndrome 17 </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/618567"> 618567 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606906"> MRM2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606906"> 606906 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/7/744?start=-3&limit=10&highlight=744"> 7q34 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/212350"> Sengers syndrome </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/212350"> 212350 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610345"> AGK </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/610345"> 610345 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/8/452?start=-3&limit=10&highlight=452"> 8q22.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612075"> Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy) </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/612075"> 612075 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604712"> RRM2B </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604712"> 604712 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/8/452?start=-3&limit=10&highlight=452"> 8q22.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612075"> Mitochondrial DNA depletion syndrome 8B (MNGIE type) </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/612075"> 612075 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604712"> RRM2B </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/604712"> 604712 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/10/214?start=-3&limit=10&highlight=214"> 10q21.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/617156"> ?Mitochondrial DNA depletion syndrome 15 (hepatocerebral type) </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/617156"> 617156 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600438"> TFAM </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/600438"> 600438 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/10/489?start=-3&limit=10&highlight=489"> 10q24.31 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/271245"> Mitochondrial DNA depletion syndrome 7 (hepatocerebral type) </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/271245"> 271245 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606075"> TWNK </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606075"> 606075 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/13/158?start=-3&limit=10&highlight=158"> 13q14.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612073"> Mitochondrial DNA depletion syndrome 5 (encephalomyopathic with or without methylmalonic aciduria) </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/612073"> 612073 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603921"> SUCLA2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603921"> 603921 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/14/182?start=-3&limit=10&highlight=182"> 14q13.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/618811"> ?Mitochondrial DNA depletion syndrome 18 </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/618811"> 618811 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607571"> SLC25A21 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607571"> 607571 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/15/498?start=-3&limit=10&highlight=498"> 15q26.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/613662"> Mitochondrial DNA depletion syndrome 4B (MNGIE type) </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/613662"> 613662 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/174763"> POLG </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/174763"> 174763 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/15/498?start=-3&limit=10&highlight=498"> 15q26.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/203700"> Mitochondrial DNA depletion syndrome 4A (Alpers type) </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/203700"> 203700 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/174763"> POLG </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/174763"> 174763 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/16/511?start=-3&limit=10&highlight=511"> 16q21 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/609560"> Mitochondrial DNA depletion syndrome 2 (myopathic type) </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>
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<a href="/entry/619425"> ?Mitochondrial DNA depletion syndrome 16B (neuroophthalmic type) </a>
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<a href="/entry/603041"> Mitochondrial DNA depletion syndrome 1 (MNGIE type) </a>
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because mitochondrial DNA depletion syndrome-3 (MTDPS3) is caused by homozygous or compound heterozygous mutation in the DGUOK gene (<a href="/entry/601465">601465</a>) on chromosome 2p13.</p><p>Biallelic mutation in the DGUOK gene can also cause adult-onset PEOB4 (<a href="/entry/617070">617070</a>).</p>
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<p>Mitochondrial DNA depletion syndrome-3 is a severe autosomal recessive disorder characterized by onset in infancy of progressive liver failure and neurologic abnormalities, hypoglycemia, and increased lactate in body fluids. Affected tissues show both decreased activity of the mtDNA-encoded respiratory chain complexes (I, III, IV, and V) and mtDNA depletion (<a href="#9" class="mim-tip-reference" title="Mandel, H., Szargel, R., Labay, V., Elpeleg, O., Saada, A., Shalata, A., Anbinder, Y., Berkowitz, D., Hartman, C., Barak, M., Eriksson, S., Cohen, N. <strong>The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA.</strong> Nature Genet. 29: 337-341, 2001. Note: Erratum: Nature Genet. 29: 491 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11687800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11687800</a>] [<a href="https://doi.org/10.1038/ng746" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11687800">Mandel et al., 2001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11687800" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (<a href="/entry/603041">603041</a>).</p>
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<p><a href="#3" class="mim-tip-reference" title="Boustany, R. N., Aprille, J. R., Halperin, J., Levy, H., DeLong, G. R. <strong>Mitochondrial cytochrome deficiency presenting as a myopathy with hypotonia, external ophthalmoplegia, and lactic acidosis in an infant and as fatal hepatopathy in a second cousin.</strong> Ann. Neurol. 14: 462-470, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6314875/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6314875</a>] [<a href="https://doi.org/10.1002/ana.410140411" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6314875">Boustany et al. (1983)</a> reported a patient who died at age 9 months of hepatic failure with generalized aminoaciduria, but without lactic acidosis or muscle involvement. Liver biopsy showed enlarged mitochondria and decreased cytochrome c oxidase activity (less than 10% of normal). Kidney mitochondria showed normal cytochromes. A second cousin, related through the maternal grandfather, had a fatal mitochondrial myopathy characterized by progressive generalized hypotonia, progressive external ophthalmoplegia, and severe lactic acidosis. In an addendum, the authors noted that another family member presented at 2 months of age with hypotonia, ophthalmoplegia, and lactic acidosis. In tissue samples from the patient reported by <a href="#3" class="mim-tip-reference" title="Boustany, R. N., Aprille, J. R., Halperin, J., Levy, H., DeLong, G. R. <strong>Mitochondrial cytochrome deficiency presenting as a myopathy with hypotonia, external ophthalmoplegia, and lactic acidosis in an infant and as fatal hepatopathy in a second cousin.</strong> Ann. Neurol. 14: 462-470, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6314875/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6314875</a>] [<a href="https://doi.org/10.1002/ana.410140411" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6314875">Boustany et al. (1983)</a>, <a href="#11" class="mim-tip-reference" title="Moraes, C. T., Shanske, S., Tritschler, H.-J., Aprille, J. R., Andreetta, F., Bonilla, E., Schon, E. A., DiMauro, S. <strong>mtDNA depletion with variable tissue expression: a novel genetic abnormality in mitochondrial diseases.</strong> Am. J. Hum. Genet. 48: 492-501, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1998336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1998336</a>]" pmid="1998336">Moraes et al. (1991)</a> found a quantitative defect of mtDNA involving liver (12% of control values). There was no evidence of an mtDNA mutation in the areas surrounding the origin of replication of the heavy strand (H-strand) or light strand (L-strand) of mtDNA. <a href="#11" class="mim-tip-reference" title="Moraes, C. T., Shanske, S., Tritschler, H.-J., Aprille, J. R., Andreetta, F., Bonilla, E., Schon, E. A., DiMauro, S. <strong>mtDNA depletion with variable tissue expression: a novel genetic abnormality in mitochondrial diseases.</strong> Am. J. Hum. Genet. 48: 492-501, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1998336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1998336</a>]" pmid="1998336">Moraes et al. (1991)</a> concluded that affected individuals exhibit variable levels of mtDNA depletion (up to 98%) in affected tissues, while unaffected tissues have relatively normal levels of mtDNA. In addition, different tissues may be involved in related patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1998336+6314875" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Mazziotta, M. R. M., Ricci, E., Bertini, E., Vici, C. D., Servidei, S., Burlina, A. B., Sabetta, G., Bartuli, A., Manfredi, G., Silvestri, G., Moraes, C. T., DiMauro, S. <strong>Fatal infantile liver failure associated with mitochondrial DNA depletion.</strong> J. Pediat. 121: 896-901, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1447652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1447652</a>] [<a href="https://doi.org/10.1016/s0022-3476(05)80335-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1447652">Mazziotta et al. (1992)</a> reported a 3-month-old girl who presented with frequent vomiting and hypotonia. She had severe metabolic acidosis, hepatomegaly, and rapidly progressive fatal liver failure with death at age 4 months. Mitochondrial DNA was 90% depleted in liver and activity of mitochondrial-encoded respiratory chain enzymes were markedly decreased. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1447652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Bodnar, A. G., Cooper, J. M., Holt, I. J., Leonard, J. V., Schapira, A. H. V. <strong>Nuclear complementation restores mtDNA levels in cultured cells from a patient with mtDNA depletion.</strong> Am. J. Hum. Genet. 53: 663-669, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8394647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8394647</a>]" pmid="8394647">Bodnar et al. (1993)</a> studied fibroblasts from a patient described by <a href="#7" class="mim-tip-reference" title="Leonard, J. V., Hyland, K., Furukawa, N., Clayton, P. T. <strong>Mitochondrial phosphoenolpyruvate carboxykinase deficiency.</strong> Europ. J. Pediat. 150: 198-199, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2044592/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2044592</a>] [<a href="https://doi.org/10.1007/BF01963566" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2044592">Leonard et al. (1991)</a>. The fourth child of healthy, unrelated parents and the product of an uncomplicated full-term pregnancy, the infant soon after birth developed progressive liver failure, widespread edema, hyponatremia, hypoalbuminemia, marked prolongation of clotting times, and lactic acidosis. He became progressively more hypotonic and unresponsive and died at 4 months of age. An older sister had a clinically similar illness and died at 4 months of age. One older brother was noted to be hypertonic and jittery on the second day of life and died suddenly and unexpectedly at 4 weeks of age. Clinical presentation and family history were similar to those reported for cases of mtDNA depletion. Studies on cultured skin fibroblasts from patient 1 revealed a decrease in activities of the respiratory-chain enzymes and a quantitative decrease in mtDNA. It was also observed that the fibroblasts were dependent on uridine and pyruvate for growth, which is a well-characterized requirement for rho(0) cells, which have been depleted of mtDNA by long-term exposure to low concentrations of ethidium bromide. This property of the patient's fibroblasts provided a selectable marker for experiments performed by <a href="#2" class="mim-tip-reference" title="Bodnar, A. G., Cooper, J. M., Holt, I. J., Leonard, J. V., Schapira, A. H. V. <strong>Nuclear complementation restores mtDNA levels in cultured cells from a patient with mtDNA depletion.</strong> Am. J. Hum. Genet. 53: 663-669, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8394647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8394647</a>]" pmid="8394647">Bodnar et al. (1993)</a> because complementation of these metabolic requirements indicated the reconstitution of mitochondrial function. The nuclear genome of this patient was represented by enucleated fibroblasts and human-derived rho(0) cell lines. The resulting cybrids grew in medium lacking pyruvate and uridine, indicating restoration of respiratory chain function. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2044592+8394647" 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="#14" class="mim-tip-reference" title="Taanman, J.-W., Bodnar, A. G., Cooper, J. M., Morris, A. A. M., Clayton, P. T., Leonard, J. V., Schapira, A. H. V. <strong>Molecular mechanisms in mitochondrial DNA depletion syndrome.</strong> Hum. Molec. Genet. 6: 935-942, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9175742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9175742</a>] [<a href="https://doi.org/10.1093/hmg/6.6.935" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9175742">Taanman et al. (1997)</a> studied myoblast cell cultures from a patient with the mtDNA depletion syndrome and demonstrated complementation by normal nuclei. The patient presented at 8 weeks of age with hypotonia, poor visual fixation, and variable lactic acidemia. He died of progressive liver failure at the age of 7.5 months. <a href="#14" class="mim-tip-reference" title="Taanman, J.-W., Bodnar, A. G., Cooper, J. M., Morris, A. A. M., Clayton, P. T., Leonard, J. V., Schapira, A. H. V. <strong>Molecular mechanisms in mitochondrial DNA depletion syndrome.</strong> Hum. Molec. Genet. 6: 935-942, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9175742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9175742</a>] [<a href="https://doi.org/10.1093/hmg/6.6.935" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9175742">Taanman et al. (1997)</a> stated that the mitochondrial DNA depletion syndrome had been documented in 29 children. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9175742" 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="Blake, J. C., Taanman, J.-W., Morris, A. M. M., Gray, R. G. F., Cooper, J. M., McKiernan, P. J., Leonard, J. V., Schapira, A. H. V. <strong>Mitochondrial DNA depletion syndrome is expressed in amniotic fluid cell cultures.</strong> Am. J. Path. 155: 67-70, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10393838/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10393838</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10393838[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1016/S0002-9440(10)65100-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10393838">Blake et al. (1999)</a> reported 2 sibs with the disorder. In the proband, they used immunocytochemical techniques to demonstrate that the disorder was expressed in amniotic fluid cells. The proband, the second child in the family, was well at birth but developed hypoglycemia during the first 24 hours of life. Later, she developed lactic acidemia with progressive liver failure. Liver biopsy showed micronodular cirrhosis with proliferation of bile ducts and abundant neutral fat and bile pigment in hepatocytes. The activity of cytochrome c oxidase was severely depleted in liver. Assay of phosphoenolpyruvate carboxykinase (PEPCK; <a href="/entry/614168">614168</a>) in liver mitochondria revealed evidence of reduced mitochondrial PEPCK activity, but PEPCK activity measured in amniotic fluid cells and fibroblasts was within normal limits. The patient died of progressive liver failure at the age of 6 months. Skeletal muscle obtained at postmortem showed relatively uniform fibers with no evidence of ragged-red fibers. There was an excess of coarse lipid droplets in many muscle fibers. Cytochrome c oxidase activity was normal and present in all fibers. The patient's elder brother was well at birth but very soon developed symptoms compatible with liver failure. Blood lactate was variably increased. The child died at the age of 7 weeks of progressive liver failure. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10393838" 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="#9" class="mim-tip-reference" title="Mandel, H., Szargel, R., Labay, V., Elpeleg, O., Saada, A., Shalata, A., Anbinder, Y., Berkowitz, D., Hartman, C., Barak, M., Eriksson, S., Cohen, N. <strong>The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA.</strong> Nature Genet. 29: 337-341, 2001. Note: Erratum: Nature Genet. 29: 491 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11687800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11687800</a>] [<a href="https://doi.org/10.1038/ng746" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11687800">Mandel et al. (2001)</a> reported 19 affected members from 3 unrelated Israeli-Druze families with the hepatocerebral form of mtDNA depletion syndrome. Affected individuals presented between birth and 6 months of age with hepatic failure, severe failure to thrive, oscillating eye movements, and neurologic abnormalities, accompanied by lactic acidosis, hypoglycemia, and markedly elevated amounts of alpha-fetoprotein in plasma. Death usually occurred before 1 year of age. Enzymatic activities of the mitochondrial respiratory chain complexes containing mtDNA-encoded subunits (complexes I, III, and IV) were reduced to various extents, whereas complex II enzymatic activity, which is encoded solely by nuclear genes, was normal. Muscle tissue from 7 affected patients showed normal histology and respiratory chain complex activities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11687800" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Mancuso, M., Ferraris, S., Pancrudo, J., Feigenbaum, A., Raiman, J., Christodoulou, J., Thorburn, D. R., DiMauro, S. <strong>New DGK gene mutations in the hepatocerebral form of mitochondrial DNA depletion syndrome.</strong> Arch. Neurol. 62: 745-747, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15883261/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15883261</a>] [<a href="https://doi.org/10.1001/archneur.62.5.745" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15883261">Mancuso et al. (2005)</a> reported 2 sibs and 1 unrelated patient with hepatocerebral DNA depletion syndrome caused by mutations in the DGUOK gene. Common features included poor feeding, vomiting, failure to thrive, hypothermia, metabolic acidosis, and hypoglycemia in the neonatal period. Signs of overt liver failure developed in the first months of life with ascites, jaundice, hepatomegaly, abnormal liver function tests, hyperbilirubinemia, and coagulopathy. Liver biopsy of 2 patients showed severe micronodular cirrhosis, marked cholestasis, steatosis, hepatocellular loss, and fibrosis. Ultrastructural examination in 1 patient showed excessive and abnormal mitochondria. Liver specimens showed 84 to 90% mtDNA depletion. All patients showed variable encephalopathic signs including nystagmus, cerebral atrophy, microcephaly, hypotonia, and in 1 patient, optic dysplasia. Although 1 patient underwent liver transplantation, all 3 died by 5 months of age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15883261" 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>
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<a href="#6" class="mim-tip-reference" title="Ducluzeau, P.-H., Lachaux, A., Bouvier, R., Streichenberger, N., Stepien, G., Mousson, B. <strong>Depletion of mitochondrial DNA associated with infantile cholestasis and progressive liver fibrosis.</strong> J. Hepat. 30: 149-155, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9927162/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9927162</a>] [<a href="https://doi.org/10.1016/s0168-8278(99)80019-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9927162">Ducluzeau et al. (1999)</a> described the case of a 28-month-old French boy who presented with a transient liver cholestasis, beginning at the age of 2 months, complicated by progressive fibrosis due to liver mtDNA depletion but without extrahepatic involvement. Lactate levels and lactate/pyruvate ratio were elevated. On the third liver biopsy, micronodular cirrhosis was fully established. Mitochondrial enzyme analyses and Southern blots were abnormal in liver, but normal in skin and skeletal muscle. <a href="#5" class="mim-tip-reference" title="Ducluzeau, P.-H., Lachaux, A., Bouvier, R., Duborjal, H., Stepien, G., Bozon, D., Mousson de Camaret, B. <strong>Progressive reversion of clinical and molecular phenotype in a child with liver mitochondrial DNA depletion.</strong> J. Hepatol. 36: 698-703, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11983456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11983456</a>] [<a href="https://doi.org/10.1016/s0168-8278(02)00021-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11983456">Ducluzeau et al. (2002)</a> reported clinical follow-up of the patient reported by <a href="#6" class="mim-tip-reference" title="Ducluzeau, P.-H., Lachaux, A., Bouvier, R., Streichenberger, N., Stepien, G., Mousson, B. <strong>Depletion of mitochondrial DNA associated with infantile cholestasis and progressive liver fibrosis.</strong> J. Hepat. 30: 149-155, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9927162/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9927162</a>] [<a href="https://doi.org/10.1016/s0168-8278(99)80019-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9927162">Ducluzeau et al. (1999)</a>, who was 6 years old at the time of the second report. At about 32 months of age, the patient's liver tests began to improve spontaneously, and this was associated with an increase in clotting factors, a dramatic decrease of liver fibrosis and normal appearance of hepatocytes on biopsy, an increase in liver mtDNA content, and almost complete restoration of respiratory chain complex activities containing mtDNA-encoded subunits. He showed normal psychomotor development at age 46 months. <a href="#5" class="mim-tip-reference" title="Ducluzeau, P.-H., Lachaux, A., Bouvier, R., Duborjal, H., Stepien, G., Bozon, D., Mousson de Camaret, B. <strong>Progressive reversion of clinical and molecular phenotype in a child with liver mitochondrial DNA depletion.</strong> J. Hepatol. 36: 698-703, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11983456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11983456</a>] [<a href="https://doi.org/10.1016/s0168-8278(02)00021-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11983456">Ducluzeau et al. (2002)</a> suggested that the most probable hypotheses for such a highly unusual recovery of mtDNA level include somatic mosaicism for a mutation in the nuclear genome or spontaneous reversion to normal of one of the putative mutations. In the patient reported by <a href="#6" class="mim-tip-reference" title="Ducluzeau, P.-H., Lachaux, A., Bouvier, R., Streichenberger, N., Stepien, G., Mousson, B. <strong>Depletion of mitochondrial DNA associated with infantile cholestasis and progressive liver fibrosis.</strong> J. Hepat. 30: 149-155, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9927162/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9927162</a>] [<a href="https://doi.org/10.1016/s0168-8278(99)80019-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9927162">Ducluzeau et al. (1999)</a>, <a href="#12" class="mim-tip-reference" title="Mousson de Camaret, B., Taanman, J. W., Padet, S., Chassagne, M., Mayencon, M., Clerc-Renaud, P., Mandon, G., Zabot, M.-T., Lachaux, A., Bozon, D. <strong>Kinetic properties of mutant deoxyguanosine kinase in a case of reversible hepatic mtDNA depletion.</strong> Biochem. J. 402: 377-385, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17073823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17073823</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17073823[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1042/BJ20060705" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17073823">Mousson de Camaret et al. (2007)</a> identified compound heterozygous missense mutations in the DGUOK gene (N46S, <a href="/entry/601465#0008">601465.0008</a> and L266R, <a href="/entry/601465#0009">601465.0009</a>). In vitro studies showed that these mutations retained 10 to 14% residual enzymatic activity, which likely contributed to the unusual phenotypic reversal in this patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=11983456+17073823+9927162" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#11" class="mim-tip-reference" title="Moraes, C. T., Shanske, S., Tritschler, H.-J., Aprille, J. R., Andreetta, F., Bonilla, E., Schon, E. A., DiMauro, S. <strong>mtDNA depletion with variable tissue expression: a novel genetic abnormality in mitochondrial diseases.</strong> Am. J. Hum. Genet. 48: 492-501, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1998336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1998336</a>]" pmid="1998336">Moraes et al. (1991)</a> found no evidence of maternal inheritance, and suggested that mtDNA depletion may be inherited as an autosomal recessive disorder. Alternatively, they also suggested that this phenotype may be the result of a dominant nuclear mutation expressed only when combined with a certain mitochondrial genotype. <a href="#10" class="mim-tip-reference" title="Mazziotta, M. R. M., Ricci, E., Bertini, E., Vici, C. D., Servidei, S., Burlina, A. B., Sabetta, G., Bartuli, A., Manfredi, G., Silvestri, G., Moraes, C. T., DiMauro, S. <strong>Fatal infantile liver failure associated with mitochondrial DNA depletion.</strong> J. Pediat. 121: 896-901, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1447652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1447652</a>] [<a href="https://doi.org/10.1016/s0022-3476(05)80335-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1447652">Mazziotta et al. (1992)</a> suggested that it is an autosomal dominant trait with incomplete penetrance. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1998336+1447652" 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>All 29 patients reviewed by <a href="#14" class="mim-tip-reference" title="Taanman, J.-W., Bodnar, A. G., Cooper, J. M., Morris, A. A. M., Clayton, P. T., Leonard, J. V., Schapira, A. H. V. <strong>Molecular mechanisms in mitochondrial DNA depletion syndrome.</strong> Hum. Molec. Genet. 6: 935-942, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9175742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9175742</a>] [<a href="https://doi.org/10.1093/hmg/6.6.935" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9175742">Taanman et al. (1997)</a> were born to clinically normal parents, and family histories were compatible with autosomal recessive inheritance in all but 1 pedigree, where the pattern of inheritance could be explained by autosomal dominant transmission with incomplete penetrance (<a href="#10" class="mim-tip-reference" title="Mazziotta, M. R. M., Ricci, E., Bertini, E., Vici, C. D., Servidei, S., Burlina, A. B., Sabetta, G., Bartuli, A., Manfredi, G., Silvestri, G., Moraes, C. T., DiMauro, S. <strong>Fatal infantile liver failure associated with mitochondrial DNA depletion.</strong> J. Pediat. 121: 896-901, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1447652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1447652</a>] [<a href="https://doi.org/10.1016/s0022-3476(05)80335-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1447652">Mazziotta et al., 1992</a>). Whether recessive or dominant, the autosomal inheritance supported the involvement of a nuclear-encoded factor. Complementation with nuclear DNA from a normal cell line (<a href="#2" class="mim-tip-reference" title="Bodnar, A. G., Cooper, J. M., Holt, I. J., Leonard, J. V., Schapira, A. H. V. <strong>Nuclear complementation restores mtDNA levels in cultured cells from a patient with mtDNA depletion.</strong> Am. J. Hum. Genet. 53: 663-669, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8394647/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8394647</a>]" pmid="8394647">Bodnar et al., 1993</a>) indicated involvement of the nuclear genome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9175742+8394647+1447652" 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="Douglas, G. V., Wiszniewska, J., Lipson, M. H., Witt, D. R., McDowell, T., Sifry-Platt, M., Hirano, M., Craigen, W. J., Wong, L.-J. C. <strong>Detection of uniparental isodisomy in autosomal recessive mitochondrial DNA depletion syndrome by high-density SNP array analysis.</strong> J. Hum. Genet. 56: 834-839, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22011815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22011815</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22011815[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/jhg.2011.112" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22011815">Douglas et al. (2011)</a> reported a patient, born of unrelated Mexican parents, with classic hepatocerebral mtDNA depletion syndrome due to an apparently homozygous mutation in the DGUOK gene. However, analysis of parental DNA showed that only the father carried the mutation in the heterozygous state. Analysis of patient tissue ruled out gene deletion, and SNP array analysis showed only paternal inheritance of informative markers and no inheritance of maternal alleles. There was copy-neutral absence of heterozygosity across the entire chromosome 2, consistent with uniparental isodisomy for the DGUOK gene. The findings had implications for genetic counseling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22011815" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#9" class="mim-tip-reference" title="Mandel, H., Szargel, R., Labay, V., Elpeleg, O., Saada, A., Shalata, A., Anbinder, Y., Berkowitz, D., Hartman, C., Barak, M., Eriksson, S., Cohen, N. <strong>The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA.</strong> Nature Genet. 29: 337-341, 2001. Note: Erratum: Nature Genet. 29: 491 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11687800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11687800</a>] [<a href="https://doi.org/10.1038/ng746" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11687800">Mandel et al. (2001)</a> used homozygosity mapping in 3 kindreds of Druze origin segregating for the hepatocerebral mtDNA depletion syndrome and mapped the disorder to a region of 6.1 cM on chromosome 2p13. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11687800" 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 3 Israeli-Druze kindreds with hepatocerebral mtDNA depletion syndrome-3, <a href="#9" class="mim-tip-reference" title="Mandel, H., Szargel, R., Labay, V., Elpeleg, O., Saada, A., Shalata, A., Anbinder, Y., Berkowitz, D., Hartman, C., Barak, M., Eriksson, S., Cohen, N. <strong>The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA.</strong> Nature Genet. 29: 337-341, 2001. Note: Erratum: Nature Genet. 29: 491 only, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11687800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11687800</a>] [<a href="https://doi.org/10.1038/ng746" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11687800">Mandel et al. (2001)</a> identified a 1-bp deletion in the DGUOK gene (204delA; <a href="/entry/601465#0001">601465.0001</a>) that segregated with the disease. Western blot analysis failed to detect deoxyguanosine kinase protein in the liver of affected individuals. The main supply of deoxyribonucleotides (dNTPs) for mtDNA synthesis comes from the salvage pathway initiated by deoxyguanosine kinase and thymidine kinase-2. The association of mtDNA depletion with mutated DGUOK suggested that the salvage pathway enzymes are involved in the maintenance of balanced mitochondrial dNTP pools. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11687800" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 3 (14%) of 21 patients with hepatocerebral mtDNA depletion syndrome-3, <a href="#13" class="mim-tip-reference" title="Salviati, L., Sacconi, S., Mancuso, M., Otaegui, D., Camano, P., Marina, A., Rabinowitz, S., Shiffman, R., Thompson, K., Wilson, C. M., Feigenbaum, A., Naini, A. B., Hirano, M., Bonilla, E., DiMauro, S., Vu, T. H. <strong>Mitochondrial DNA depletion and dGK gene mutations.</strong> Ann. Neurol. 52: 311-316, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12205643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12205643</a>] [<a href="https://doi.org/10.1002/ana.10284" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12205643">Salviati et al. (2002)</a> identified mutations in the DGUOK gene (<a href="/entry/601465#0003">601465.0003</a>-<a href="/entry/601465#0006">601465.0006</a>). The findings suggested that other genes may also be responsible for mitochondrial depletion in the liver. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12205643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Tadiboyina, V. T., Rupar, A., Atkison, P. Feigenbaum, A., Kronick, J., Wang, J., Hegele, R. A. <strong>Novel mutation in DGUOK in hepatocerebral mitochondrial DNA depletion syndrome associated with cystathioninuria.</strong> Am. J. Med. Genet. 135A: 289-291, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15887277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15887277</a>] [<a href="https://doi.org/10.1002/ajmg.a.30748" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15887277">Tadiboyina et al. (2005)</a> reported 3 patients with the hepatocerebral form of mtDNA depletion syndrome together with cystathioninuria (see <a href="/entry/219500">219500</a>). All 3 children were homozygous for a D255Y mutation (<a href="/entry/601465#0007">601465.0007</a>) in the DGUOK gene but had no mutations in the cystathionine gamma-lyase gene (CTH; <a href="/entry/607657">607657</a>), indicating that the hepatocerebral form of mtDNA depletion syndrome might be associated with secondary cystathioninuria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15887277" 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 href="https://doi.org/10.1002/ana.410140411" target="_blank">Full Text</a>]
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Douglas, G. V., Wiszniewska, J., Lipson, M. H., Witt, D. R., McDowell, T., Sifry-Platt, M., Hirano, M., Craigen, W. J., Wong, L.-J. C.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22011815/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22011815</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=22011815[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22011815" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/jhg.2011.112" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11983456/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11983456</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11983456" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/BF01963566" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1001/archneur.62.5.745" target="_blank">Full Text</a>]
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Mandel, H., Szargel, R., Labay, V., Elpeleg, O., Saada, A., Shalata, A., Anbinder, Y., Berkowitz, D., Hartman, C., Barak, M., Eriksson, S., Cohen, N.
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<strong>The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA.</strong>
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Nature Genet. 29: 337-341, 2001. Note: Erratum: Nature Genet. 29: 491 only, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11687800/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11687800</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11687800" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/ng746" target="_blank">Full Text</a>]
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Mazziotta, M. R. M., Ricci, E., Bertini, E., Vici, C. D., Servidei, S., Burlina, A. B., Sabetta, G., Bartuli, A., Manfredi, G., Silvestri, G., Moraes, C. T., DiMauro, S.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1447652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1447652</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1447652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0022-3476(05)80335-x" target="_blank">Full Text</a>]
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Moraes, C. T., Shanske, S., Tritschler, H.-J., Aprille, J. R., Andreetta, F., Bonilla, E., Schon, E. A., DiMauro, S.
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<strong>mtDNA depletion with variable tissue expression: a novel genetic abnormality in mitochondrial diseases.</strong>
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Am. J. Hum. Genet. 48: 492-501, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1998336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1998336</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1998336" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="Mousson de Camaret2007" class="mim-anchor"></a>
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Mousson de Camaret, B., Taanman, J. W., Padet, S., Chassagne, M., Mayencon, M., Clerc-Renaud, P., Mandon, G., Zabot, M.-T., Lachaux, A., Bozon, D.
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<strong>Kinetic properties of mutant deoxyguanosine kinase in a case of reversible hepatic mtDNA depletion.</strong>
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Biochem. J. 402: 377-385, 2007.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17073823/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17073823</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=17073823[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17073823" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1042/BJ20060705" target="_blank">Full Text</a>]
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<a id="Salviati2002" class="mim-anchor"></a>
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Salviati, L., Sacconi, S., Mancuso, M., Otaegui, D., Camano, P., Marina, A., Rabinowitz, S., Shiffman, R., Thompson, K., Wilson, C. M., Feigenbaum, A., Naini, A. B., Hirano, M., Bonilla, E., DiMauro, S., Vu, T. H.
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<strong>Mitochondrial DNA depletion and dGK gene mutations.</strong>
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Ann. Neurol. 52: 311-316, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12205643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12205643</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12205643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.10284" target="_blank">Full Text</a>]
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<a id="14" class="mim-anchor"></a>
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<a id="Taanman1997" class="mim-anchor"></a>
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Taanman, J.-W., Bodnar, A. G., Cooper, J. M., Morris, A. A. M., Clayton, P. T., Leonard, J. V., Schapira, A. H. V.
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<strong>Molecular mechanisms in mitochondrial DNA depletion syndrome.</strong>
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Hum. Molec. Genet. 6: 935-942, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9175742/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9175742</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9175742" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/6.6.935" target="_blank">Full Text</a>]
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<a id="15" class="mim-anchor"></a>
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<a id="Tadiboyina2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tadiboyina, V. T., Rupar, A., Atkison, P. Feigenbaum, A., Kronick, J., Wang, J., Hegele, R. A.
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<strong>Novel mutation in DGUOK in hepatocerebral mitochondrial DNA depletion syndrome associated with cystathioninuria.</strong>
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Am. J. Med. Genet. 135A: 289-291, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15887277/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15887277</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15887277" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ajmg.a.30748" target="_blank">Full Text</a>]
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 08/11/2016
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Cassandra L. Kniffin - updated : 1/5/2012<br>George E. Tiller - updated : 11/2/2009<br>Cassandra L. Kniffin - updated : 10/16/2008<br>Cassandra L. Kniffin - updated : 3/31/2008<br>Victor A. McKusick - updated : 8/23/2006<br>Victor A. McKusick - updated : 4/26/2006<br>Cassandra L. Kniffin - updated : 8/31/2005<br>Marla J. F. O'Neill - updated : 7/12/2005<br>Cassandra L. Kniffin - updated : 5/23/2005<br>Cassandra L. Kniffin - updated : 8/4/2004<br>Cassandra L. Kniffin - reorganized : 9/11/2003<br>Cassandra L. Kniffin - updated : 8/7/2003<br>Victor A. McKusick - updated : 12/27/2002<br>Cassandra L. Kniffin - updated : 12/13/2002<br>Victor A. McKusick - updated : 10/19/2001<br>Victor A. McKusick - updated : 7/24/2001<br>Victor A. McKusick - updated : 9/20/1999<br>Wilson H. Y. Lo - updated : 6/25/1999<br>Victor A. McKusick - updated : 6/23/1997
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<span class="mim-text-font">
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Victor A. McKusick : 9/28/1993
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carol : 10/28/2024
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carol : 08/12/2016<br>ckniffin : 08/11/2016<br>carol : 06/21/2016<br>carol : 7/8/2014<br>carol : 1/5/2012<br>ckniffin : 1/5/2012<br>terry : 12/27/2010<br>joanna : 12/22/2010<br>carol : 12/21/2010<br>ckniffin : 12/9/2010<br>wwang : 11/2/2009<br>ckniffin : 10/12/2009<br>wwang : 10/20/2008<br>ckniffin : 10/16/2008<br>wwang : 4/4/2008<br>ckniffin : 3/31/2008<br>alopez : 8/25/2006<br>terry : 8/23/2006<br>wwang : 5/2/2006<br>terry : 4/26/2006<br>carol : 9/20/2005<br>ckniffin : 8/31/2005<br>wwang : 7/18/2005<br>terry : 7/12/2005<br>terry : 7/12/2005<br>tkritzer : 5/23/2005<br>ckniffin : 5/23/2005<br>terry : 4/6/2005<br>tkritzer : 8/13/2004<br>ckniffin : 8/4/2004<br>carol : 9/11/2003<br>ckniffin : 9/11/2003<br>ckniffin : 9/3/2003<br>tkritzer : 8/12/2003<br>ckniffin : 8/7/2003<br>cwells : 1/2/2003<br>terry : 12/27/2002<br>carol : 12/17/2002<br>ckniffin : 12/13/2002<br>alopez : 11/27/2001<br>alopez : 11/21/2001<br>cwells : 10/23/2001<br>cwells : 10/23/2001<br>cwells : 10/23/2001<br>terry : 10/19/2001<br>mcapotos : 8/8/2001<br>mcapotos : 7/31/2001<br>terry : 7/24/2001<br>jlewis : 9/29/1999<br>terry : 9/20/1999<br>carol : 6/25/1999<br>dkim : 7/24/1998<br>jenny : 6/23/1997<br>terry : 6/19/1997<br>carol : 12/13/1994<br>carol : 10/1/1993<br>carol : 9/28/1993
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<strong>#</strong> 251880
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MITOCHONDRIAL DNA DEPLETION SYNDROME 3 (HEPATOCEREBRAL TYPE); MTDPS3
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<strong>SNOMEDCT:</strong> 783734000;
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<strong>ORPHA:</strong> 279934;
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<strong>DO:</strong> 0080121;
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<strong>Phenotype-Gene Relationships</strong>
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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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2p13.1
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Mitochondrial DNA depletion syndrome 3 (hepatocerebral type)
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251880
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Autosomal recessive
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3
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DGUOK
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601465
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because mitochondrial DNA depletion syndrome-3 (MTDPS3) is caused by homozygous or compound heterozygous mutation in the DGUOK gene (601465) on chromosome 2p13.</p><p>Biallelic mutation in the DGUOK gene can also cause adult-onset PEOB4 (617070).</p>
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<strong>Description</strong>
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<p>Mitochondrial DNA depletion syndrome-3 is a severe autosomal recessive disorder characterized by onset in infancy of progressive liver failure and neurologic abnormalities, hypoglycemia, and increased lactate in body fluids. Affected tissues show both decreased activity of the mtDNA-encoded respiratory chain complexes (I, III, IV, and V) and mtDNA depletion (Mandel et al., 2001). </p><p>For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (603041).</p>
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<strong>Clinical Features</strong>
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<p>Boustany et al. (1983) reported a patient who died at age 9 months of hepatic failure with generalized aminoaciduria, but without lactic acidosis or muscle involvement. Liver biopsy showed enlarged mitochondria and decreased cytochrome c oxidase activity (less than 10% of normal). Kidney mitochondria showed normal cytochromes. A second cousin, related through the maternal grandfather, had a fatal mitochondrial myopathy characterized by progressive generalized hypotonia, progressive external ophthalmoplegia, and severe lactic acidosis. In an addendum, the authors noted that another family member presented at 2 months of age with hypotonia, ophthalmoplegia, and lactic acidosis. In tissue samples from the patient reported by Boustany et al. (1983), Moraes et al. (1991) found a quantitative defect of mtDNA involving liver (12% of control values). There was no evidence of an mtDNA mutation in the areas surrounding the origin of replication of the heavy strand (H-strand) or light strand (L-strand) of mtDNA. Moraes et al. (1991) concluded that affected individuals exhibit variable levels of mtDNA depletion (up to 98%) in affected tissues, while unaffected tissues have relatively normal levels of mtDNA. In addition, different tissues may be involved in related patients. </p><p>Mazziotta et al. (1992) reported a 3-month-old girl who presented with frequent vomiting and hypotonia. She had severe metabolic acidosis, hepatomegaly, and rapidly progressive fatal liver failure with death at age 4 months. Mitochondrial DNA was 90% depleted in liver and activity of mitochondrial-encoded respiratory chain enzymes were markedly decreased. </p><p>Bodnar et al. (1993) studied fibroblasts from a patient described by Leonard et al. (1991). The fourth child of healthy, unrelated parents and the product of an uncomplicated full-term pregnancy, the infant soon after birth developed progressive liver failure, widespread edema, hyponatremia, hypoalbuminemia, marked prolongation of clotting times, and lactic acidosis. He became progressively more hypotonic and unresponsive and died at 4 months of age. An older sister had a clinically similar illness and died at 4 months of age. One older brother was noted to be hypertonic and jittery on the second day of life and died suddenly and unexpectedly at 4 weeks of age. Clinical presentation and family history were similar to those reported for cases of mtDNA depletion. Studies on cultured skin fibroblasts from patient 1 revealed a decrease in activities of the respiratory-chain enzymes and a quantitative decrease in mtDNA. It was also observed that the fibroblasts were dependent on uridine and pyruvate for growth, which is a well-characterized requirement for rho(0) cells, which have been depleted of mtDNA by long-term exposure to low concentrations of ethidium bromide. This property of the patient's fibroblasts provided a selectable marker for experiments performed by Bodnar et al. (1993) because complementation of these metabolic requirements indicated the reconstitution of mitochondrial function. The nuclear genome of this patient was represented by enucleated fibroblasts and human-derived rho(0) cell lines. The resulting cybrids grew in medium lacking pyruvate and uridine, indicating restoration of respiratory chain function. </p><p>Taanman et al. (1997) studied myoblast cell cultures from a patient with the mtDNA depletion syndrome and demonstrated complementation by normal nuclei. The patient presented at 8 weeks of age with hypotonia, poor visual fixation, and variable lactic acidemia. He died of progressive liver failure at the age of 7.5 months. Taanman et al. (1997) stated that the mitochondrial DNA depletion syndrome had been documented in 29 children. </p><p>Blake et al. (1999) reported 2 sibs with the disorder. In the proband, they used immunocytochemical techniques to demonstrate that the disorder was expressed in amniotic fluid cells. The proband, the second child in the family, was well at birth but developed hypoglycemia during the first 24 hours of life. Later, she developed lactic acidemia with progressive liver failure. Liver biopsy showed micronodular cirrhosis with proliferation of bile ducts and abundant neutral fat and bile pigment in hepatocytes. The activity of cytochrome c oxidase was severely depleted in liver. Assay of phosphoenolpyruvate carboxykinase (PEPCK; 614168) in liver mitochondria revealed evidence of reduced mitochondrial PEPCK activity, but PEPCK activity measured in amniotic fluid cells and fibroblasts was within normal limits. The patient died of progressive liver failure at the age of 6 months. Skeletal muscle obtained at postmortem showed relatively uniform fibers with no evidence of ragged-red fibers. There was an excess of coarse lipid droplets in many muscle fibers. Cytochrome c oxidase activity was normal and present in all fibers. The patient's elder brother was well at birth but very soon developed symptoms compatible with liver failure. Blood lactate was variably increased. The child died at the age of 7 weeks of progressive liver failure. </p><p>Mandel et al. (2001) reported 19 affected members from 3 unrelated Israeli-Druze families with the hepatocerebral form of mtDNA depletion syndrome. Affected individuals presented between birth and 6 months of age with hepatic failure, severe failure to thrive, oscillating eye movements, and neurologic abnormalities, accompanied by lactic acidosis, hypoglycemia, and markedly elevated amounts of alpha-fetoprotein in plasma. Death usually occurred before 1 year of age. Enzymatic activities of the mitochondrial respiratory chain complexes containing mtDNA-encoded subunits (complexes I, III, and IV) were reduced to various extents, whereas complex II enzymatic activity, which is encoded solely by nuclear genes, was normal. Muscle tissue from 7 affected patients showed normal histology and respiratory chain complex activities. </p><p>Mancuso et al. (2005) reported 2 sibs and 1 unrelated patient with hepatocerebral DNA depletion syndrome caused by mutations in the DGUOK gene. Common features included poor feeding, vomiting, failure to thrive, hypothermia, metabolic acidosis, and hypoglycemia in the neonatal period. Signs of overt liver failure developed in the first months of life with ascites, jaundice, hepatomegaly, abnormal liver function tests, hyperbilirubinemia, and coagulopathy. Liver biopsy of 2 patients showed severe micronodular cirrhosis, marked cholestasis, steatosis, hepatocellular loss, and fibrosis. Ultrastructural examination in 1 patient showed excessive and abnormal mitochondria. Liver specimens showed 84 to 90% mtDNA depletion. All patients showed variable encephalopathic signs including nystagmus, cerebral atrophy, microcephaly, hypotonia, and in 1 patient, optic dysplasia. Although 1 patient underwent liver transplantation, all 3 died by 5 months of age. </p><p><strong><em>Clinical Variability</em></strong></p><p>
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Ducluzeau et al. (1999) described the case of a 28-month-old French boy who presented with a transient liver cholestasis, beginning at the age of 2 months, complicated by progressive fibrosis due to liver mtDNA depletion but without extrahepatic involvement. Lactate levels and lactate/pyruvate ratio were elevated. On the third liver biopsy, micronodular cirrhosis was fully established. Mitochondrial enzyme analyses and Southern blots were abnormal in liver, but normal in skin and skeletal muscle. Ducluzeau et al. (2002) reported clinical follow-up of the patient reported by Ducluzeau et al. (1999), who was 6 years old at the time of the second report. At about 32 months of age, the patient's liver tests began to improve spontaneously, and this was associated with an increase in clotting factors, a dramatic decrease of liver fibrosis and normal appearance of hepatocytes on biopsy, an increase in liver mtDNA content, and almost complete restoration of respiratory chain complex activities containing mtDNA-encoded subunits. He showed normal psychomotor development at age 46 months. Ducluzeau et al. (2002) suggested that the most probable hypotheses for such a highly unusual recovery of mtDNA level include somatic mosaicism for a mutation in the nuclear genome or spontaneous reversion to normal of one of the putative mutations. In the patient reported by Ducluzeau et al. (1999), Mousson de Camaret et al. (2007) identified compound heterozygous missense mutations in the DGUOK gene (N46S, 601465.0008 and L266R, 601465.0009). In vitro studies showed that these mutations retained 10 to 14% residual enzymatic activity, which likely contributed to the unusual phenotypic reversal in this patient. </p>
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<strong>Inheritance</strong>
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<p>Moraes et al. (1991) found no evidence of maternal inheritance, and suggested that mtDNA depletion may be inherited as an autosomal recessive disorder. Alternatively, they also suggested that this phenotype may be the result of a dominant nuclear mutation expressed only when combined with a certain mitochondrial genotype. Mazziotta et al. (1992) suggested that it is an autosomal dominant trait with incomplete penetrance. </p><p>All 29 patients reviewed by Taanman et al. (1997) were born to clinically normal parents, and family histories were compatible with autosomal recessive inheritance in all but 1 pedigree, where the pattern of inheritance could be explained by autosomal dominant transmission with incomplete penetrance (Mazziotta et al., 1992). Whether recessive or dominant, the autosomal inheritance supported the involvement of a nuclear-encoded factor. Complementation with nuclear DNA from a normal cell line (Bodnar et al., 1993) indicated involvement of the nuclear genome. </p><p>Douglas et al. (2011) reported a patient, born of unrelated Mexican parents, with classic hepatocerebral mtDNA depletion syndrome due to an apparently homozygous mutation in the DGUOK gene. However, analysis of parental DNA showed that only the father carried the mutation in the heterozygous state. Analysis of patient tissue ruled out gene deletion, and SNP array analysis showed only paternal inheritance of informative markers and no inheritance of maternal alleles. There was copy-neutral absence of heterozygosity across the entire chromosome 2, consistent with uniparental isodisomy for the DGUOK gene. The findings had implications for genetic counseling. </p>
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<strong>Mapping</strong>
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<p>Mandel et al. (2001) used homozygosity mapping in 3 kindreds of Druze origin segregating for the hepatocerebral mtDNA depletion syndrome and mapped the disorder to a region of 6.1 cM on chromosome 2p13. </p>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<p>In 3 Israeli-Druze kindreds with hepatocerebral mtDNA depletion syndrome-3, Mandel et al. (2001) identified a 1-bp deletion in the DGUOK gene (204delA; 601465.0001) that segregated with the disease. Western blot analysis failed to detect deoxyguanosine kinase protein in the liver of affected individuals. The main supply of deoxyribonucleotides (dNTPs) for mtDNA synthesis comes from the salvage pathway initiated by deoxyguanosine kinase and thymidine kinase-2. The association of mtDNA depletion with mutated DGUOK suggested that the salvage pathway enzymes are involved in the maintenance of balanced mitochondrial dNTP pools. </p><p>In 3 (14%) of 21 patients with hepatocerebral mtDNA depletion syndrome-3, Salviati et al. (2002) identified mutations in the DGUOK gene (601465.0003-601465.0006). The findings suggested that other genes may also be responsible for mitochondrial depletion in the liver. </p><p>Tadiboyina et al. (2005) reported 3 patients with the hepatocerebral form of mtDNA depletion syndrome together with cystathioninuria (see 219500). All 3 children were homozygous for a D255Y mutation (601465.0007) in the DGUOK gene but had no mutations in the cystathionine gamma-lyase gene (CTH; 607657), indicating that the hepatocerebral form of mtDNA depletion syndrome might be associated with secondary cystathioninuria. </p>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<strong>Mitochondrial DNA depletion syndrome is expressed in amniotic fluid cell cultures.</strong>
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Bodnar, A. G., Cooper, J. M., Holt, I. J., Leonard, J. V., Schapira, A. H. V.
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<strong>Nuclear complementation restores mtDNA levels in cultured cells from a patient with mtDNA depletion.</strong>
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Boustany, R. N., Aprille, J. R., Halperin, J., Levy, H., DeLong, G. R.
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Douglas, G. V., Wiszniewska, J., Lipson, M. H., Witt, D. R., McDowell, T., Sifry-Platt, M., Hirano, M., Craigen, W. J., Wong, L.-J. C.
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<strong>Detection of uniparental isodisomy in autosomal recessive mitochondrial DNA depletion syndrome by high-density SNP array analysis.</strong>
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J. Hum. Genet. 56: 834-839, 2011.
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<p class="mim-text-font">
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Ducluzeau, P.-H., Lachaux, A., Bouvier, R., Duborjal, H., Stepien, G., Bozon, D., Mousson de Camaret, B.
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<strong>Progressive reversion of clinical and molecular phenotype in a child with liver mitochondrial DNA depletion.</strong>
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J. Hepatol. 36: 698-703, 2002.
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Ducluzeau, P.-H., Lachaux, A., Bouvier, R., Streichenberger, N., Stepien, G., Mousson, B.
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<strong>Depletion of mitochondrial DNA associated with infantile cholestasis and progressive liver fibrosis.</strong>
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J. Hepat. 30: 149-155, 1999.
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Leonard, J. V., Hyland, K., Furukawa, N., Clayton, P. T.
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<strong>Mitochondrial phosphoenolpyruvate carboxykinase deficiency.</strong>
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Europ. J. Pediat. 150: 198-199, 1991.
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Mancuso, M., Ferraris, S., Pancrudo, J., Feigenbaum, A., Raiman, J., Christodoulou, J., Thorburn, D. R., DiMauro, S.
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<strong>New DGK gene mutations in the hepatocerebral form of mitochondrial DNA depletion syndrome.</strong>
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Arch. Neurol. 62: 745-747, 2005.
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[Full Text: https://doi.org/10.1001/archneur.62.5.745]
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Mandel, H., Szargel, R., Labay, V., Elpeleg, O., Saada, A., Shalata, A., Anbinder, Y., Berkowitz, D., Hartman, C., Barak, M., Eriksson, S., Cohen, N.
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<strong>The deoxyguanosine kinase gene is mutated in individuals with depleted hepatocerebral mitochondrial DNA.</strong>
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Nature Genet. 29: 337-341, 2001. Note: Erratum: Nature Genet. 29: 491 only, 2001.
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[PubMed: 11687800]
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[Full Text: https://doi.org/10.1038/ng746]
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Mazziotta, M. R. M., Ricci, E., Bertini, E., Vici, C. D., Servidei, S., Burlina, A. B., Sabetta, G., Bartuli, A., Manfredi, G., Silvestri, G., Moraes, C. T., DiMauro, S.
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<strong>Fatal infantile liver failure associated with mitochondrial DNA depletion.</strong>
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Moraes, C. T., Shanske, S., Tritschler, H.-J., Aprille, J. R., Andreetta, F., Bonilla, E., Schon, E. A., DiMauro, S.
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<strong>mtDNA depletion with variable tissue expression: a novel genetic abnormality in mitochondrial diseases.</strong>
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Am. J. Hum. Genet. 48: 492-501, 1991.
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<p class="mim-text-font">
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Mousson de Camaret, B., Taanman, J. W., Padet, S., Chassagne, M., Mayencon, M., Clerc-Renaud, P., Mandon, G., Zabot, M.-T., Lachaux, A., Bozon, D.
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<strong>Kinetic properties of mutant deoxyguanosine kinase in a case of reversible hepatic mtDNA depletion.</strong>
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Biochem. J. 402: 377-385, 2007.
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<p class="mim-text-font">
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Salviati, L., Sacconi, S., Mancuso, M., Otaegui, D., Camano, P., Marina, A., Rabinowitz, S., Shiffman, R., Thompson, K., Wilson, C. M., Feigenbaum, A., Naini, A. B., Hirano, M., Bonilla, E., DiMauro, S., Vu, T. H.
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<strong>Mitochondrial DNA depletion and dGK gene mutations.</strong>
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<p class="mim-text-font">
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Taanman, J.-W., Bodnar, A. G., Cooper, J. M., Morris, A. A. M., Clayton, P. T., Leonard, J. V., Schapira, A. H. V.
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<strong>Molecular mechanisms in mitochondrial DNA depletion syndrome.</strong>
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Hum. Molec. Genet. 6: 935-942, 1997.
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[PubMed: 9175742]
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[Full Text: https://doi.org/10.1093/hmg/6.6.935]
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Tadiboyina, V. T., Rupar, A., Atkison, P. Feigenbaum, A., Kronick, J., Wang, J., Hegele, R. A.
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<strong>Novel mutation in DGUOK in hepatocerebral mitochondrial DNA depletion syndrome associated with cystathioninuria.</strong>
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Am. J. Med. Genet. 135A: 289-291, 2005.
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[PubMed: 15887277]
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[Full Text: https://doi.org/10.1002/ajmg.a.30748]
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<span class="text-nowrap mim-text-font">
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Contributors:
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</span>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 08/11/2016<br>Cassandra L. Kniffin - updated : 1/5/2012<br>George E. Tiller - updated : 11/2/2009<br>Cassandra L. Kniffin - updated : 10/16/2008<br>Cassandra L. Kniffin - updated : 3/31/2008<br>Victor A. McKusick - updated : 8/23/2006<br>Victor A. McKusick - updated : 4/26/2006<br>Cassandra L. Kniffin - updated : 8/31/2005<br>Marla J. F. O'Neill - updated : 7/12/2005<br>Cassandra L. Kniffin - updated : 5/23/2005<br>Cassandra L. Kniffin - updated : 8/4/2004<br>Cassandra L. Kniffin - reorganized : 9/11/2003<br>Cassandra L. Kniffin - updated : 8/7/2003<br>Victor A. McKusick - updated : 12/27/2002<br>Cassandra L. Kniffin - updated : 12/13/2002<br>Victor A. McKusick - updated : 10/19/2001<br>Victor A. McKusick - updated : 7/24/2001<br>Victor A. McKusick - updated : 9/20/1999<br>Wilson H. Y. Lo - updated : 6/25/1999<br>Victor A. McKusick - updated : 6/23/1997
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Creation Date:
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Victor A. McKusick : 9/28/1993
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carol : 10/28/2024<br>carol : 08/12/2016<br>ckniffin : 08/11/2016<br>carol : 06/21/2016<br>carol : 7/8/2014<br>carol : 1/5/2012<br>ckniffin : 1/5/2012<br>terry : 12/27/2010<br>joanna : 12/22/2010<br>carol : 12/21/2010<br>ckniffin : 12/9/2010<br>wwang : 11/2/2009<br>ckniffin : 10/12/2009<br>wwang : 10/20/2008<br>ckniffin : 10/16/2008<br>wwang : 4/4/2008<br>ckniffin : 3/31/2008<br>alopez : 8/25/2006<br>terry : 8/23/2006<br>wwang : 5/2/2006<br>terry : 4/26/2006<br>carol : 9/20/2005<br>ckniffin : 8/31/2005<br>wwang : 7/18/2005<br>terry : 7/12/2005<br>terry : 7/12/2005<br>tkritzer : 5/23/2005<br>ckniffin : 5/23/2005<br>terry : 4/6/2005<br>tkritzer : 8/13/2004<br>ckniffin : 8/4/2004<br>carol : 9/11/2003<br>ckniffin : 9/11/2003<br>ckniffin : 9/3/2003<br>tkritzer : 8/12/2003<br>ckniffin : 8/7/2003<br>cwells : 1/2/2003<br>terry : 12/27/2002<br>carol : 12/17/2002<br>ckniffin : 12/13/2002<br>alopez : 11/27/2001<br>alopez : 11/21/2001<br>cwells : 10/23/2001<br>cwells : 10/23/2001<br>cwells : 10/23/2001<br>terry : 10/19/2001<br>mcapotos : 8/8/2001<br>mcapotos : 7/31/2001<br>terry : 7/24/2001<br>jlewis : 9/29/1999<br>terry : 9/20/1999<br>carol : 6/25/1999<br>dkim : 7/24/1998<br>jenny : 6/23/1997<br>terry : 6/19/1997<br>carol : 12/13/1994<br>carol : 10/1/1993<br>carol : 9/28/1993
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