3269 lines
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Entry
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- #603471 - CITRULLINEMIA, TYPE II, ADULT-ONSET; CTLN2
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- OMIM
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<p>
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<span class="h4">#603471</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/603471"><strong>Clinical Synopsis</strong></a>
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<li role="presentation">
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<a href="/phenotypicSeries/PS215700"> <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="#biochemicalFeatures">Biochemical Features</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="#pathogenesis">Pathogenesis</a>
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<a href="#clinicalManagement">Clinical Management</a>
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<a href="#populationGenetics">Population Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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<div class="panel-body small mim-panel-body">
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<div><a href="https://clinicaltrials.gov/search?cond=CITRULLINEMIA, TYPE II, ADULT-ONSET" 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=19528&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1181/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/1652" 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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=603471[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=247585" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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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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</div>
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</a>
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</span>
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</span>
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</div>
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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:0070342" 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/603471" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0070342" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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<span 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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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 716863007<br />
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<strong>ORPHA:</strong> 247585<br />
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<strong>DO:</strong> 0070342<br />
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">ICD+</a>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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603471
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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CITRULLINEMIA, TYPE II, ADULT-ONSET; CTLN2
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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CITRIN DEFICIENCY
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="phenotypeMap" class="mim-anchor"></a>
|
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<h4>
|
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<span class="mim-font">
|
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<strong>Phenotype-Gene Relationships</strong>
|
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</span>
|
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</h4>
|
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<div>
|
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
|
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<a href="/geneMap/7/434?start=-3&limit=10&highlight=434">
|
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7q21.3
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</a>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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Citrullinemia, adult-onset type II
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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/603471"> 603471 </a>
|
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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SLC25A13
|
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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/603859"> 603859 </a>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group ">
|
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<a href="/clinicalSynopsis/603471" 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/PS215700" 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/603471" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/603471" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<div>
|
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<p />
|
|
</div>
|
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|
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<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">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
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|
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<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ABDOMEN </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Liver </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Nonalcoholic fatty liver disease <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/197315008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">197315008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1231824009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1231824009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K76.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K76.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0400966&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0400966</a>]</span><br /> -
|
|
Hepatic 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/197321007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">197321007</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=C0015695&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015695</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 /> -
|
|
Hepatic fibrosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/62484002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">62484002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K74.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K74.00</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K74.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K74.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0239946&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239946</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001395" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001395</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001395" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001395</a>]</span><br /> -
|
|
Hepatocyte ballooning <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3276178&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3276178</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Pancreas </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Pancreatitis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/75694006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">75694006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K85.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K85.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0030305&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0030305</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001733" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001733</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001733" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001733</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEUROLOGIC </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Central Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Sudden onset of neuropsychiatric symptoms <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3276177&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3276177</a>]</span><br /> -
|
|
Disorientation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/62476001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">62476001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/286933003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">286933003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R41.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R41.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0009676&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009676</a>, <a href="https://bioportal.bioontology.org/search?q=C0233407&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0233407</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001289" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001289</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001289" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001289</a>]</span><br /> -
|
|
Confusion <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/40917007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">40917007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/286933003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">286933003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R41.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R41.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0009676&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009676</a>, <a href="https://bioportal.bioontology.org/search?q=C0683369&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0683369</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001289" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001289</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001289" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001289</a>]</span><br /> -
|
|
Disturbance of consciousness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/3006004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">3006004</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/780.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">780.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234428&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234428</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004372" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004372</a>]</span><br /> -
|
|
Coma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/371632003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">371632003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405809000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405809000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R40.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R40.20</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R40.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R40.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/780.01" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">780.01</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0543874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0543874</a>, <a href="https://bioportal.bioontology.org/search?q=C3146279&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3146279</a>, <a href="https://bioportal.bioontology.org/search?q=C0009421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009421</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001259" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001259</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001259" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001259</a>]</span><br /> -
|
|
Brain edema <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/2032001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">2032001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G93.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G93.6</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/348.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">348.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0006114&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0006114</a>, <a href="https://bioportal.bioontology.org/search?q=C1527311&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1527311</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002181" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002181</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002181" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002181</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
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|
|
</div>
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</div>
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|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEOPLASIA </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Hepatocellular carcinoma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/109841003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">109841003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/187769009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">187769009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1186630006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1186630006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/25370001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">25370001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/C22.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">C22.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2239176&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2239176</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001402" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001402</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001402" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001402</a>]</span><br />
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</span>
|
|
</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> LABORATORY ABNORMALITIES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Hyperammonemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/9360008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">9360008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E72.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E72.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5574662&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5574662</a>, <a href="https://bioportal.bioontology.org/search?q=C0220994&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0220994</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001987" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001987</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001987" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001987</a>]</span><br /> -
|
|
Citrullinemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/124711003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">124711003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398680004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398680004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E72.23" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E72.23</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0175683&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0175683</a>]</span><br /> -
|
|
Abnormal liver enzymes <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/166643006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">166643006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0438237&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0438237</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002910" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002910</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002910" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002910</a>]</span><br /> -
|
|
Low serum albumin <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0580493&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0580493</a>]</span><br /> -
|
|
Increased serum triglycerides <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/166848004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">166848004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0813230&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0813230</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002155" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002155</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002155" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002155</a>]</span><br /> -
|
|
Increased serum pancreatic secretory trypsin inhibitor (PSTI) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3276179&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3276179</a>]</span><br /> -
|
|
Secondary decreased activity of argininosuccinate synthetase (ASS1) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3276180&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3276180</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Mean age of diagnosis is 40 years (range 11 to 79 years)<br /> -
|
|
Some patients may be asymptomatic<br /> -
|
|
Natural aversion to carbohydrates<br /> -
|
|
Favoring of fat and protein<br /> -
|
|
Increased frequency in individuals of Asian descent<br /> -
|
|
1 in 19,000 in Japan<br /> -
|
|
1 in 50,000 in Korea<br /> -
|
|
1 in 17,000 in China<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Caused by mutation in the solute carrier family 25 (mitochondrial carrier, citrin), member 13 (SLC25A13, <a href="/entry/603859#0001">603859.0001</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Citrullinemia
|
|
- <a href="/phenotypicSeries/PS215700">PS215700</a>
|
|
- 3 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/7/434?start=-3&limit=10&highlight=434"> 7q21.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605814"> Citrullinemia, type II, neonatal-onset </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/605814"> 605814 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603859"> SLC25A13 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603859"> 603859 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/7/434?start=-3&limit=10&highlight=434"> 7q21.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603471"> Citrullinemia, adult-onset type II </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603471"> 603471 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603859"> SLC25A13 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603859"> 603859 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/9/577?start=-3&limit=10&highlight=577"> 9q34.11 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/215700"> Citrullinemia </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/215700"> 215700 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603470"> ASS1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603470"> 603470 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="text-right small">
|
|
<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
|
|
|
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
|
|
<span class="mim-font">
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<p>A number sign (#) is used with this entry because adult-onset type II citrullinemia, also known as citrin deficiency, is caused by homozygous or compound heterozygous mutation in the SLC25A13 gene (<a href="/entry/603859">603859</a>) on chromosome 7q21.</p><p>Neonatal-onset type II citrullinemia (<a href="/entry/605814">605814</a>) is caused by mutation in the same gene.</p><p>Classic citrullinemia (CTLN1; <a href="/entry/215700">215700</a>) is a genetically distinct disorder caused by mutation in the gene encoding argininosuccinate synthetase (ASS1; <a href="/entry/603470">603470</a>).</p>
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<p>Adult-onset type II citrullinemia is an autosomal recessive metabolic disorder characterized clinically by the sudden onset of various neuropsychologic symptoms such as disorientation, abnormal behavior, convulsions, and coma due to hyperammonemia. In some cases, rapid progression can lead to brain edema and death if liver transplantation is not possible. Some patients may present with nonalcoholic hepatic steatosis or may develop hepatic fibrosis or hepatocellular carcinoma. Patients with this disorder have a natural aversion to carbohydrates and favor protein, which is in contrast to protein aversion usually observed in patients with urea cycle defects (summary by <a href="#5" class="mim-tip-reference" title="Komatsu, M., Yazaki, M., Tanaka, N., Sano, K., Hashimoto, E., Takei, Y., Song, Y.-Z., Tanaka, E., Kiyosawa, K., Saheki, T., Aoyama, T., Kobayashi, K. <strong>Citrin deficiency as a cause of chronic liver disorder mimicking non-alcoholic fatty liver disease.</strong> J. Hepatol. 49: 810-820, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18620775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18620775</a>] [<a href="https://doi.org/10.1016/j.jhep.2008.05.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18620775">Komatsu et al., 2008</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18620775" 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 Japan a distinct late-onset form of citrullinemia was reported; see review by <a href="#14" class="mim-tip-reference" title="Walser, M. <strong>Urea cycle disorders and other hereditary hyperammonemic syndromes. In: Stanbury, J. B.; Wyngaarden, J. B.; Fredrickson, D. S.; Goldstein, J. L.; Brown, M. S. (eds.): The Metabolic Basis of Inherited Disease. (5th ed.)</strong> New York: McGraw-Hill (pub.) 1983. Pp. 402-438."None>Walser (1983)</a>. Significant clinical abnormality had onset in childhood or not until adulthood, age 48 years in 1 case. Symptoms included enuresis, delayed menarche, insomnia, sleep reversal, nocturnal sweats and terrors, recurrent vomiting (especially at night), diarrhea, tremors, episodes of confusion after meals, lethargy, convulsions, delusions, hallucinations, and brief episodes of coma. Delayed mental and physical development was shown by some patients. Most had a peculiar fondness for beans, peas, and peanuts from early childhood and a dislike for rice, other vegetables, and sweets. Since the preferred foods are high in arginine, the dietary predilection of these patients may reflect an arginine deficiency. As the patients get older, episodic disturbances become more frequent, and bizarre behavior, including manic episodes, echolalia, and frank psychosis, appears. Citrulline concentrations in the plasma were increased. The late-onset form is apparently autosomal recessive because sibs have been affected and some of the parents have been consanguineous. Most of the reports of the late-onset form appeared in Japanese journals; see <a href="#14" class="mim-tip-reference" title="Walser, M. <strong>Urea cycle disorders and other hereditary hyperammonemic syndromes. In: Stanbury, J. B.; Wyngaarden, J. B.; Fredrickson, D. S.; Goldstein, J. L.; Brown, M. S. (eds.): The Metabolic Basis of Inherited Disease. (5th ed.)</strong> New York: McGraw-Hill (pub.) 1983. Pp. 402-438."None>Walser (1983)</a> for references. An exception was the report by <a href="#7" class="mim-tip-reference" title="Matsuda, I., Anakura, M., Arashima, S., Saito, Y., Oka, Y. <strong>Variant form of citrullinemia.</strong> J. Pediat. 88: 824-826, 1976.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1271146/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1271146</a>] [<a href="https://doi.org/10.1016/s0022-3476(76)81123-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1271146">Matsuda et al. (1976)</a>. Also see <a href="#13" class="mim-tip-reference" title="Scott-Emuakpor, A., Higgins, J. V., Kohrman, A. F. <strong>Citrullinemia: a new case, with implications concerning adaptation to defective urea synthesis.</strong> Pediat. Res. 6: 626-633, 1972.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5057291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5057291</a>]" pmid="5057291">Scott-Emuakpor et al. (1972)</a> for a similar case reported from the United States. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5057291+1271146" 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 the study of adult-onset type II citrullinemia in Japanese, <a href="#16" class="mim-tip-reference" title="Yasuda, T., Yamaguchi, N., Kobayashi, K., Nishi, I., Horinouchi, H., Jalil, M. A., Li, M. X., Ushikai, M., Iijima, M., Kondo, I., Saheki, T. <strong>Identification of two novel mutations in the SLC25A13 gene and detection of seven mutations in 102 patients with adult-onset type II citrullinemia.</strong> Hum. Genet. 107: 537-545, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11153906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11153906</a>] [<a href="https://doi.org/10.1007/s004390000430" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11153906">Yasuda et al. (2000)</a> found that the onset of serious and recurring symptoms in CTLN2 varied from age 11 to age 79, with a mean of 34.4 years. Almost all patients suffered from a sudden disturbance of consciousness associated with disorientation, restlessness, drowsiness, and coma, and most died mainly of cerebral edema within a few years of onset. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11153906" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Komatsu, M., Yazaki, M., Tanaka, N., Sano, K., Hashimoto, E., Takei, Y., Song, Y.-Z., Tanaka, E., Kiyosawa, K., Saheki, T., Aoyama, T., Kobayashi, K. <strong>Citrin deficiency as a cause of chronic liver disorder mimicking non-alcoholic fatty liver disease.</strong> J. Hepatol. 49: 810-820, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18620775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18620775</a>] [<a href="https://doi.org/10.1016/j.jhep.2008.05.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18620775">Komatsu et al. (2008)</a> found that 17 (89%) of 19 patients with genetically confirmed CTLN2 had hepatic steatosis. Four (21%) had been diagnosed with nonalcoholic fatty liver disease before the appearance of neuropsychologic symptoms that are usually characteristic of CTLN2. Hepatic steatosis occurred in the absence of obesity or features of the metabolic syndrome; all patients were lean. Some patients showed hepatic fibrosis, suggesting progression of liver damage. Laboratory abnormalities in CTLN2 patients included citrullinemia, abnormal liver enzymes, low albumin, increased serum triglycerides, and decreased activity of argininosuccinate synthetase. CTLN2 patients had a higher frequency of pancreatitis compared to those without mutations. Increased levels of pancreatic secretory protease inhibitor (PSTI, SPINK1; <a href="/entry/167790">167790</a>) were associated with citrin deficiency, which could be a useful method of distinguishing CTLN2 patients from those with nonalcoholic fatty liver disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18620775" 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="Batshaw, M. L., Tuchman, M., Summar, M., Seminara, J., Members of the Urea Cycle Disorders Consortium. <strong>A longitudinal study of urea cycle disorders.</strong> Molec. Genet. Metab. 113: 127-130, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25135652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25135652</a>] [<a href="https://doi.org/10.1016/j.ymgme.2014.08.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25135652">Batshaw et al. (2014)</a> reported the results of an analysis of 614 patients with urea cycle disorders (UCDs) enrolled in the Urea Cycle Disorders Consortium's longitudinal study protocol. Citrullinemia type II occurred in 2 patients (0.3%), of whom 1 had the late-onset form and the other the neonatal form. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25135652" 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>Most patients with adult-onset citrullinemia in Japan were found to have type II citrullinemia, which is associated with decreased activity of argininosuccinate synthetase activity and protein in the liver but normal ASS1 levels in other tissues such as kidney, brain, and fibroblasts. Patients suffer from a disturbance of consciousness, such as disorientation, restlessness, and coma, and may die with cerebral edema within a few years of onset. Although there is a decrease in ASS enzyme protein with normal kinetic properties, there was no apparent abnormality in the amount, translational activity, or gross structure of hepatic ASS mRNA (<a href="#3" class="mim-tip-reference" title="Kobayashi, K., Shaheen, N., Kumashiro, R., Tanikawa, K., O'Brien, W. E., Beaudet, A. L., Saheki, T. <strong>A search for the primary abnormality in adult-onset type II citrullinemia.</strong> Am. J. Hum. Genet. 53: 1024-1030, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8105687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8105687</a>]" pmid="8105687">Kobayashi et al., 1993</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8105687" 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="#4" class="mim-tip-reference" title="Kobayashi, K., Sinasac, D. S., Iijima, M., Boright, A. P., Begum, L., Lee, J. R., Yasuda, T., Ikeda, S., Hirano, R., Terazono, H., Crackower, M. A., Kondo, I., Tsui, L.-C., Scherer, S. W., Saheki, T. <strong>The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein.</strong> Nature Genet. 22: 159-163, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369257/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369257</a>] [<a href="https://doi.org/10.1038/9667" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10369257">Kobayashi et al. (1999)</a> studied 118 CTLN2 families in Japan and localized the CTLN2 locus to chromosome 7q21.3 by homozygosity mapping analysis of individuals from 18 consanguineous unions. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10369257" 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="#3" class="mim-tip-reference" title="Kobayashi, K., Shaheen, N., Kumashiro, R., Tanikawa, K., O'Brien, W. E., Beaudet, A. L., Saheki, T. <strong>A search for the primary abnormality in adult-onset type II citrullinemia.</strong> Am. J. Hum. Genet. 53: 1024-1030, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8105687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8105687</a>]" pmid="8105687">Kobayashi et al. (1993)</a> found on sequence analysis no mutation in the ASS1 mRNA from 2 patients with adult-onset type II citrullinemia. They also reported RFLP analysis of a consanguineous family with type II citrullinemia in which 3 polymorphisms located within the ASS1 gene locus were examined. In spite of having consanguineous parents, the patient was not homozygous for the ASS1 gene haplotype. The RFLP analysis of 16 affected patients from consanguineous parents showed that 5 of 16 had the heterozygous pattern for 1 of the 3 DNA probes and that the frequency of the heterozygous haplotype was not different from the control frequency. These results suggested that the primary defect of type II citrullinemia was not within the ASS1 gene locus. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8105687" 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>Pathogenic Mutations in the SLC25A13 Gene</em></strong></p><p>
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In 18 adult patients with CTLN2 from consanguineous parents, <a href="#4" class="mim-tip-reference" title="Kobayashi, K., Sinasac, D. S., Iijima, M., Boright, A. P., Begum, L., Lee, J. R., Yasuda, T., Ikeda, S., Hirano, R., Terazono, H., Crackower, M. A., Kondo, I., Tsui, L.-C., Scherer, S. W., Saheki, T. <strong>The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein.</strong> Nature Genet. 22: 159-163, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369257/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369257</a>] [<a href="https://doi.org/10.1038/9667" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10369257">Kobayashi et al. (1999)</a> identified 5 distinct mutations (<a href="/entry/603859#0001">603859.0001</a>-<a href="/entry/603859#0005">603859.0005</a>) in the SLC25A13 gene, encoding citrin, and confirmed their causative role in the disease. The studies of adult-onset type II citrullinemia in Japanese were extended by <a href="#16" class="mim-tip-reference" title="Yasuda, T., Yamaguchi, N., Kobayashi, K., Nishi, I., Horinouchi, H., Jalil, M. A., Li, M. X., Ushikai, M., Iijima, M., Kondo, I., Saheki, T. <strong>Identification of two novel mutations in the SLC25A13 gene and detection of seven mutations in 102 patients with adult-onset type II citrullinemia.</strong> Hum. Genet. 107: 537-545, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11153906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11153906</a>] [<a href="https://doi.org/10.1007/s004390000430" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11153906">Yasuda et al. (2000)</a>, who identified 2 novel mutations in the SLC25A13 gene (see, e.g., <a href="/entry/603859">603859</a>). Diagnostic analysis for the 7 known mutations in 103 CTLN2 patients diagnosed by biochemical and enzymatic studies revealed that 102 patients had 1 or 2 of the 7 mutations and 93 patients were homozygotes or compound heterozygotes. Five of 22 patients from consanguineous unions were compound heterozygotes, suggesting a high frequency of the mutated genes. The frequency of homozygotes was calculated to be more than 1 in 20,000 from carrier detection (6 in 400 individuals tested) in the Japanese population. By Western blot analysis with antihuman citrin antibody, the authors detected no cross-reactive immune materials in the liver of CTLN2 patients with any of the 7 mutations. From these findings, <a href="#16" class="mim-tip-reference" title="Yasuda, T., Yamaguchi, N., Kobayashi, K., Nishi, I., Horinouchi, H., Jalil, M. A., Li, M. X., Ushikai, M., Iijima, M., Kondo, I., Saheki, T. <strong>Identification of two novel mutations in the SLC25A13 gene and detection of seven mutations in 102 patients with adult-onset type II citrullinemia.</strong> Hum. Genet. 107: 537-545, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11153906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11153906</a>] [<a href="https://doi.org/10.1007/s004390000430" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11153906">Yasuda et al. (2000)</a> hypothesized that CTLN2 is caused by a complete deletion of citrin, although this did not explain the mechanism of argininosuccinate synthetase deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10369257+11153906" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 38-year-old Pakistani man living in Europe who had episodic confusion, elevated plasma ammonia and arginine levels, citrullinemia, normal glutamine, low serine levels, and fatal hyperammonemic encephalopathy, <a href="#2" class="mim-tip-reference" title="Fiermonte, G., Soon, D., Chaudhuri, A., Paradies, E., Lee, P. J., Krywawych, S., Palmieri, F., Lachmann, R. H. <strong>An adult with type 2 citrullinemia presenting in Europe. (Letter)</strong> New Eng. J. Med. 358: 1408-1409, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18367750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18367750</a>] [<a href="https://doi.org/10.1056/NEJMc0707353" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18367750">Fiermonte et al. (2008)</a> identified homozygosity for a mutation at a highly conserved residue in the SLC25A13 gene (R588Q; <a href="/entry/603859#0007">603859.0007</a>). The authors noted that type II citrullinemia has rarely been reported outside of East Asia but must be considered in adults presenting with hyperammonemic encephalopathy, since the management is different from the management of classic urea-cycle defects (see <a href="/entry/311250">311250</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18367750" 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="Saheki, T., Kobayashi, K. <strong>Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD).</strong> J. Hum. Genet. 47: 333-341, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12111366/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12111366</a>] [<a href="https://doi.org/10.1007/s100380200046" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12111366">Saheki and Kobayashi (2002)</a> concluded that citrin deficiency causes 2 different phenotypes, NICCD in neonates (<a href="/entry/605814">605814</a>) and CTLN2 in adults, through the additional effects of genetic or environmental modifiers. Since citrin and aralar (SLC25A12; <a href="/entry/603667">603667</a>) are mitochondrial aspartate glutamate carriers, the various symptoms of NICCD and CTLN2 may be caused by defective aspartate export from the mitochondria to the cytosol and defects in the malate aspartate shuttle. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12111366" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Komatsu, M., Yazaki, M., Tanaka, N., Sano, K., Hashimoto, E., Takei, Y., Song, Y.-Z., Tanaka, E., Kiyosawa, K., Saheki, T., Aoyama, T., Kobayashi, K. <strong>Citrin deficiency as a cause of chronic liver disorder mimicking non-alcoholic fatty liver disease.</strong> J. Hepatol. 49: 810-820, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18620775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18620775</a>] [<a href="https://doi.org/10.1016/j.jhep.2008.05.016" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18620775">Komatsu et al. (2008)</a> hypothesized that the hepatic steatosis observed in patients with CTLN2 may result from a compensatory upregulation of the malate-citrate shuttle, which increases citrate in the cytosol, resulting in increased acetyl-CoA and an overproduction of fatty acids in hepatocytes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18620775" 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="#10" class="mim-tip-reference" title="Saheki, T., Inoue, K., Tushima, A., Mutoh, K., Kobayashi, K. <strong>Citrin deficiency and current treatment concepts.</strong> Molec. Genet. Metab. 100 (Suppl. 1): S59-S64, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20233664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20233664</a>] [<a href="https://doi.org/10.1016/j.ymgme.2010.02.014" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20233664">Saheki et al. (2010)</a> noted that conventional treatments for hyperammonemia and brain edema, such as glycerol, are harmful in patients with CTLN2 because use of carbohydrates can exacerbate hyperammonemia. The most effective treatment for this disorder is liver transplantation, although many patients can be managed by a low-carbohydrate/high-protein diet. Use of dietary arginine or sodium pyruvate may also be potentially therapeutic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20233664" 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="#4" class="mim-tip-reference" title="Kobayashi, K., Sinasac, D. S., Iijima, M., Boright, A. P., Begum, L., Lee, J. R., Yasuda, T., Ikeda, S., Hirano, R., Terazono, H., Crackower, M. A., Kondo, I., Tsui, L.-C., Scherer, S. W., Saheki, T. <strong>The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein.</strong> Nature Genet. 22: 159-163, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369257/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369257</a>] [<a href="https://doi.org/10.1038/9667" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10369257">Kobayashi et al. (1999)</a> stated that the frequency of CTLN2 in Japan is approximately 1 in 100,000. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10369257" 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="#16" class="mim-tip-reference" title="Yasuda, T., Yamaguchi, N., Kobayashi, K., Nishi, I., Horinouchi, H., Jalil, M. A., Li, M. X., Ushikai, M., Iijima, M., Kondo, I., Saheki, T. <strong>Identification of two novel mutations in the SLC25A13 gene and detection of seven mutations in 102 patients with adult-onset type II citrullinemia.</strong> Hum. Genet. 107: 537-545, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11153906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11153906</a>] [<a href="https://doi.org/10.1007/s004390000430" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11153906">Yasuda et al. (2000)</a> calculated the frequency of homozygotes of SLC25A13 mutations to be more than 1 in 20,000 from carrier detection (6 in 400 individuals tested) in the Japanese population. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11153906" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Among 1,315 Japanese individuals tested, <a href="#15" class="mim-tip-reference" title="Yamaguchi, N., Kobayashi, K., Yasuda, T., Nishi, I., Iijima, M., Nakagawa, M., Osame, M., Kondo, I., Saheki, T. <strong>Screening of SLC25A13 mutations in early and late onset patients with citrin deficiency and in the Japanese population: identification of two novel mutations and establishment of multiple DNA diagnosis methods for nine mutations.</strong> Hum. Mutat. 19: 122-130, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11793471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11793471</a>] [<a href="https://doi.org/10.1002/humu.10022" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11793471">Yamaguchi et al. (2002)</a> found that 18 were carriers of an SLC25A13 mutation; this provided an estimate of minimally 1 in 21,000 for homozygotes. They referred to 2 Chinese CTLN2 patients in Taiwan and a Vietnamese neonatal-onset type II citrullinemia (NICCD) patient in Australia who had the same SLC25A13 mutations as those identified in Japanese patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11793471" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Lu, Y. B., Kobayashi, K., Ushikai, M., Tabata, A., Iijima, M., Li, M. X., Lei, L., Kawabe, K., Taura, S., Yang, Y., Liu, T.-T., Chiang, S.-H., Hsiao, K.-J., Lau, Y.-L., Tsui, L.-C., Lee, D. H., Saheki, T. <strong>Frequency and distribution in East Asia of 12 mutations identified in the SLC25A13 gene of Japanese patients with citrin deficiency.</strong> J. Hum. Genet. 50: 338-346, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16059747/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16059747</a>] [<a href="https://doi.org/10.1007/s10038-005-0262-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="16059747">Lu et al. (2005)</a> estimated the frequencies of SLC25A13 homozygotes to be 1 in 19,000 in Japan, 1 in 50,000 in Korea, and 1 in 17,000 in China. Specific mutations were identified in all Asian countries tested, with the most common mutations being a 4-bp deletion (<a href="/entry/603859#0001">603859.0001</a>) and a splice site mutation (<a href="/entry/603859#0002">603859.0002</a>). The frequencies of SLC25A13 homozygotes in China were calculated to be 1 in 9,200 to the south of the Yangtze River and 1 in 3,500,000 to the north of the Yangtze River. The findings were consistent with the historical boundary of the Yangtze River; modern Chinese are thought to derive from 2 distinct populations, 1 originating in the Yellow River valley and the other in the Yangtze River valley, during early Neolithic times (3,000 to 7,000 years ago). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16059747" 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>Slc25a13-knockout mice show reduced mitochondrial Asp transport, but have no apparent phenotype, likely due to increased hepatic activity of mitochondrial glycerol-3-phosphate dehydrogenase (GPD2; <a href="/entry/138430">138430</a>), which can transport NADH reducing equivalents into mitochondria. <a href="#9" class="mim-tip-reference" title="Saheki, T., Iijima, M., Li, M. X., Kobayashi, K., Horiuchi, M., Ushikai, M., Okumura, F., Meng, X. J., Inoue, I., Tajima, A., Moriyama, M., Eto, K., Kadowaki, T., Sinasac, D. S., Tsui, L.-C., Tsuji, M., Okano, A., Kobayashi, T. <strong>Citrin/mitochondrial glycerol-3-phosphate dehydrogenase double knock-out mice recapitulate features of human citrin deficiency.</strong> J. Biol. Chem. 282: 25041-25052, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17591776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17591776</a>] [<a href="https://doi.org/10.1074/jbc.M702031200" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17591776">Saheki et al. (2007)</a> found that mice with a combined disruption of the Slc25a13 and Gpd2 genes had poor growth and developed citrullinemia, hyperammonemia, hypoglycemia, and fatty liver, all features of human citrin deficiency. An altered cytosolic NADH/NAD(+) ratio was closely associated with hyperammonemia. The data indicated that the more severe phenotype present in the Slc25a13/Gpd2 double-knockout mice represents a more accurate model of human citrin deficiency than Slc25a13-knockout mice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17591776" 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="#Matsuda1979" class="mim-tip-reference" title="Matsuda, I., Arashima, S., Imanishi, Y., Yamamoto, J., Akaboshi, I., Shinozuka, S., Nagata, N. <strong>Lysine intolerance in a variant form of citrullinemia.</strong> Pediat. Res. 13: 1134-1136, 1979.">Matsuda et al. (1979)</a>; <a href="#Sase1985" class="mim-tip-reference" title="Sase, M., Kobayashi, K., Imamura, Y., Saheki, T., Nakano, K., Miura, S., Mori, M. <strong>Level of translatable messenger RNA coding for argininosuccinate synthetase in the liver of the patients with quantitative-type citrullinemia.</strong> Hum. Genet. 69: 130-134, 1985.">Sase et al. (1985)</a>
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Molec. Genet. Metab. 113: 127-130, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25135652/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25135652</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25135652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<strong>An adult with type 2 citrullinemia presenting in Europe. (Letter)</strong>
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New Eng. J. Med. 358: 1408-1409, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18367750/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18367750</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18367750" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
|
Kobayashi, K., Shaheen, N., Kumashiro, R., Tanikawa, K., O'Brien, W. E., Beaudet, A. L., Saheki, T.
|
|
<strong>A search for the primary abnormality in adult-onset type II citrullinemia.</strong>
|
|
Am. J. Hum. Genet. 53: 1024-1030, 1993.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8105687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8105687</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8105687" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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|
|
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|
|
|
|
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|
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|
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<a id="Kobayashi1999" class="mim-anchor"></a>
|
|
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|
|
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|
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Kobayashi, K., Sinasac, D. S., Iijima, M., Boright, A. P., Begum, L., Lee, J. R., Yasuda, T., Ikeda, S., Hirano, R., Terazono, H., Crackower, M. A., Kondo, I., Tsui, L.-C., Scherer, S. W., Saheki, T.
|
|
<strong>The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein.</strong>
|
|
Nature Genet. 22: 159-163, 1999.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10369257/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10369257</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10369257" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
|
[<a href="https://doi.org/10.1038/9667" target="_blank">Full Text</a>]
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|
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|
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|
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|
|
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|
|
|
|
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|
|
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|
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|
|
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|
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|
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Komatsu, M., Yazaki, M., Tanaka, N., Sano, K., Hashimoto, E., Takei, Y., Song, Y.-Z., Tanaka, E., Kiyosawa, K., Saheki, T., Aoyama, T., Kobayashi, K.
|
|
<strong>Citrin deficiency as a cause of chronic liver disorder mimicking non-alcoholic fatty liver disease.</strong>
|
|
J. Hepatol. 49: 810-820, 2008.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18620775/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18620775</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18620775" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
|
|
|
|
|
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[<a href="https://doi.org/10.1016/j.jhep.2008.05.016" target="_blank">Full Text</a>]
|
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|
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|
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|
|
|
|
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|
|
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|
|
<a id="Lu2005" class="mim-anchor"></a>
|
|
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|
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|
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Lu, Y. B., Kobayashi, K., Ushikai, M., Tabata, A., Iijima, M., Li, M. X., Lei, L., Kawabe, K., Taura, S., Yang, Y., Liu, T.-T., Chiang, S.-H., Hsiao, K.-J., Lau, Y.-L., Tsui, L.-C., Lee, D. H., Saheki, T.
|
|
<strong>Frequency and distribution in East Asia of 12 mutations identified in the SLC25A13 gene of Japanese patients with citrin deficiency.</strong>
|
|
J. Hum. Genet. 50: 338-346, 2005.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16059747/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16059747</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16059747" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
|
|
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[<a href="https://doi.org/10.1007/s10038-005-0262-8" target="_blank">Full Text</a>]
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|
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|
|
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|
|
|
|
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|
|
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|
|
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|
|
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|
|
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|
|
Matsuda, I., Anakura, M., Arashima, S., Saito, Y., Oka, Y.
|
|
<strong>Variant form of citrullinemia.</strong>
|
|
J. Pediat. 88: 824-826, 1976.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1271146/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1271146</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1271146" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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[<a href="https://doi.org/10.1016/s0022-3476(76)81123-7" target="_blank">Full Text</a>]
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|
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|
|
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|
|
|
|
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|
|
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|
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|
|
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|
|
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|
|
Matsuda, I., Arashima, S., Imanishi, Y., Yamamoto, J., Akaboshi, I., Shinozuka, S., Nagata, N.
|
|
<strong>Lysine intolerance in a variant form of citrullinemia.</strong>
|
|
Pediat. Res. 13: 1134-1136, 1979.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/503639/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">503639</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=503639" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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|
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|
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[<a href="https://doi.org/10.1203/00006450-197910000-00010" target="_blank">Full Text</a>]
|
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|
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|
|
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|
|
|
|
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|
|
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|
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|
|
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|
|
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Saheki, T., Iijima, M., Li, M. X., Kobayashi, K., Horiuchi, M., Ushikai, M., Okumura, F., Meng, X. J., Inoue, I., Tajima, A., Moriyama, M., Eto, K., Kadowaki, T., Sinasac, D. S., Tsui, L.-C., Tsuji, M., Okano, A., Kobayashi, T.
|
|
<strong>Citrin/mitochondrial glycerol-3-phosphate dehydrogenase double knock-out mice recapitulate features of human citrin deficiency.</strong>
|
|
J. Biol. Chem. 282: 25041-25052, 2007.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17591776/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17591776</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17591776" 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/10.1074/jbc.M702031200" target="_blank">Full Text</a>]
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|
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|
|
|
|
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|
|
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|
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|
|
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|
|
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|
|
Saheki, T., Inoue, K., Tushima, A., Mutoh, K., Kobayashi, K.
|
|
<strong>Citrin deficiency and current treatment concepts.</strong>
|
|
Molec. Genet. Metab. 100 (Suppl. 1): S59-S64, 2010.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20233664/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20233664</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20233664" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2010.02.014" target="_blank">Full Text</a>]
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|
|
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|
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Saheki, T., Kobayashi, K.
|
|
<strong>Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD).</strong>
|
|
J. Hum. Genet. 47: 333-341, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12111366/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12111366</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12111366" 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/s100380200046" target="_blank">Full Text</a>]
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|
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<a id="Sase1985" class="mim-anchor"></a>
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|
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|
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Sase, M., Kobayashi, K., Imamura, Y., Saheki, T., Nakano, K., Miura, S., Mori, M.
|
|
<strong>Level of translatable messenger RNA coding for argininosuccinate synthetase in the liver of the patients with quantitative-type citrullinemia.</strong>
|
|
Hum. Genet. 69: 130-134, 1985.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3972414/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3972414</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3972414" 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/BF00293282" target="_blank">Full Text</a>]
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|
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|
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Scott-Emuakpor, A., Higgins, J. V., Kohrman, A. F.
|
|
<strong>Citrullinemia: a new case, with implications concerning adaptation to defective urea synthesis.</strong>
|
|
Pediat. Res. 6: 626-633, 1972.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5057291/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5057291</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5057291" 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="Walser1983" class="mim-anchor"></a>
|
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Walser, M.
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<strong>Urea cycle disorders and other hereditary hyperammonemic syndromes. In: Stanbury, J. B.; Wyngaarden, J. B.; Fredrickson, D. S.; Goldstein, J. L.; Brown, M. S. (eds.): The Metabolic Basis of Inherited Disease. (5th ed.)</strong>
|
|
New York: McGraw-Hill (pub.) 1983. Pp. 402-438.
|
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|
|
|
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|
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|
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Yamaguchi, N., Kobayashi, K., Yasuda, T., Nishi, I., Iijima, M., Nakagawa, M., Osame, M., Kondo, I., Saheki, T.
|
|
<strong>Screening of SLC25A13 mutations in early and late onset patients with citrin deficiency and in the Japanese population: identification of two novel mutations and establishment of multiple DNA diagnosis methods for nine mutations.</strong>
|
|
Hum. Mutat. 19: 122-130, 2002.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11793471/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11793471</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11793471" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.10022" target="_blank">Full Text</a>]
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Yasuda, T., Yamaguchi, N., Kobayashi, K., Nishi, I., Horinouchi, H., Jalil, M. A., Li, M. X., Ushikai, M., Iijima, M., Kondo, I., Saheki, T.
|
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<strong>Identification of two novel mutations in the SLC25A13 gene and detection of seven mutations in 102 patients with adult-onset type II citrullinemia.</strong>
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Hum. Genet. 107: 537-545, 2000.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11153906/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11153906</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11153906" 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/s004390000430" target="_blank">Full Text</a>]
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Ada Hamosh - updated : 1/8/2015
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Cassandra L. Kniffin - updated : 7/19/2011<br>Marla J. F. O'Neill - updated : 6/25/2008<br>Cassandra L. Kniffin - updated : 11/8/2005<br>Ada Hamosh - updated : 9/22/2003<br>Cassandra L. Kniffin - reorganized : 8/15/2002<br>Victor A. McKusick - updated : 2/26/2002<br>Victor A. McKusick - updated : 5/31/1999
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Victor A. McKusick : 1/28/1999
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carol : 07/07/2016<br>alopez : 1/8/2015<br>wwang : 7/29/2011<br>ckniffin : 7/19/2011<br>wwang : 7/2/2008<br>terry : 6/25/2008<br>wwang : 11/16/2005<br>wwang : 11/16/2005<br>ckniffin : 11/8/2005<br>alopez : 9/22/2003<br>alopez : 9/22/2003<br>carol : 8/15/2002<br>ckniffin : 8/15/2002<br>carol : 2/26/2002<br>carol : 4/3/2001<br>mcapotos : 1/18/2001<br>carol : 6/1/1999<br>carol : 5/31/1999<br>carol : 5/26/1999
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<span class="mim-font">
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<strong>#</strong> 603471
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</h3>
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CITRULLINEMIA, TYPE II, ADULT-ONSET; CTLN2
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</h3>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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CITRIN DEFICIENCY
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<strong>SNOMEDCT:</strong> 716863007;
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<strong>ORPHA:</strong> 247585;
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<strong>DO:</strong> 0070342;
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<strong>Phenotype-Gene Relationships</strong>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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<span class="mim-font">
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7q21.3
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<span class="mim-font">
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Citrullinemia, adult-onset type II
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<span class="mim-font">
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603471
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<span class="mim-font">
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Autosomal recessive
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<span class="mim-font">
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3
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SLC25A13
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<span class="mim-font">
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603859
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because adult-onset type II citrullinemia, also known as citrin deficiency, is caused by homozygous or compound heterozygous mutation in the SLC25A13 gene (603859) on chromosome 7q21.</p><p>Neonatal-onset type II citrullinemia (605814) is caused by mutation in the same gene.</p><p>Classic citrullinemia (CTLN1; 215700) is a genetically distinct disorder caused by mutation in the gene encoding argininosuccinate synthetase (ASS1; 603470).</p>
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<strong>Description</strong>
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<p>Adult-onset type II citrullinemia is an autosomal recessive metabolic disorder characterized clinically by the sudden onset of various neuropsychologic symptoms such as disorientation, abnormal behavior, convulsions, and coma due to hyperammonemia. In some cases, rapid progression can lead to brain edema and death if liver transplantation is not possible. Some patients may present with nonalcoholic hepatic steatosis or may develop hepatic fibrosis or hepatocellular carcinoma. Patients with this disorder have a natural aversion to carbohydrates and favor protein, which is in contrast to protein aversion usually observed in patients with urea cycle defects (summary by Komatsu et al., 2008). </p>
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<h4>
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<strong>Clinical Features</strong>
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<p>In Japan a distinct late-onset form of citrullinemia was reported; see review by Walser (1983). Significant clinical abnormality had onset in childhood or not until adulthood, age 48 years in 1 case. Symptoms included enuresis, delayed menarche, insomnia, sleep reversal, nocturnal sweats and terrors, recurrent vomiting (especially at night), diarrhea, tremors, episodes of confusion after meals, lethargy, convulsions, delusions, hallucinations, and brief episodes of coma. Delayed mental and physical development was shown by some patients. Most had a peculiar fondness for beans, peas, and peanuts from early childhood and a dislike for rice, other vegetables, and sweets. Since the preferred foods are high in arginine, the dietary predilection of these patients may reflect an arginine deficiency. As the patients get older, episodic disturbances become more frequent, and bizarre behavior, including manic episodes, echolalia, and frank psychosis, appears. Citrulline concentrations in the plasma were increased. The late-onset form is apparently autosomal recessive because sibs have been affected and some of the parents have been consanguineous. Most of the reports of the late-onset form appeared in Japanese journals; see Walser (1983) for references. An exception was the report by Matsuda et al. (1976). Also see Scott-Emuakpor et al. (1972) for a similar case reported from the United States. </p><p>In the study of adult-onset type II citrullinemia in Japanese, Yasuda et al. (2000) found that the onset of serious and recurring symptoms in CTLN2 varied from age 11 to age 79, with a mean of 34.4 years. Almost all patients suffered from a sudden disturbance of consciousness associated with disorientation, restlessness, drowsiness, and coma, and most died mainly of cerebral edema within a few years of onset. </p><p>Komatsu et al. (2008) found that 17 (89%) of 19 patients with genetically confirmed CTLN2 had hepatic steatosis. Four (21%) had been diagnosed with nonalcoholic fatty liver disease before the appearance of neuropsychologic symptoms that are usually characteristic of CTLN2. Hepatic steatosis occurred in the absence of obesity or features of the metabolic syndrome; all patients were lean. Some patients showed hepatic fibrosis, suggesting progression of liver damage. Laboratory abnormalities in CTLN2 patients included citrullinemia, abnormal liver enzymes, low albumin, increased serum triglycerides, and decreased activity of argininosuccinate synthetase. CTLN2 patients had a higher frequency of pancreatitis compared to those without mutations. Increased levels of pancreatic secretory protease inhibitor (PSTI, SPINK1; 167790) were associated with citrin deficiency, which could be a useful method of distinguishing CTLN2 patients from those with nonalcoholic fatty liver disease. </p><p>Batshaw et al. (2014) reported the results of an analysis of 614 patients with urea cycle disorders (UCDs) enrolled in the Urea Cycle Disorders Consortium's longitudinal study protocol. Citrullinemia type II occurred in 2 patients (0.3%), of whom 1 had the late-onset form and the other the neonatal form. </p>
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<h4>
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<span class="mim-font">
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<strong>Biochemical Features</strong>
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<span class="mim-text-font">
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<p>Most patients with adult-onset citrullinemia in Japan were found to have type II citrullinemia, which is associated with decreased activity of argininosuccinate synthetase activity and protein in the liver but normal ASS1 levels in other tissues such as kidney, brain, and fibroblasts. Patients suffer from a disturbance of consciousness, such as disorientation, restlessness, and coma, and may die with cerebral edema within a few years of onset. Although there is a decrease in ASS enzyme protein with normal kinetic properties, there was no apparent abnormality in the amount, translational activity, or gross structure of hepatic ASS mRNA (Kobayashi et al., 1993). </p>
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</span>
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<h4>
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<span class="mim-font">
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<strong>Mapping</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Kobayashi et al. (1999) studied 118 CTLN2 families in Japan and localized the CTLN2 locus to chromosome 7q21.3 by homozygosity mapping analysis of individuals from 18 consanguineous unions. </p>
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</span>
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<div>
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<br />
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<span class="mim-text-font">
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<p><strong><em>Exclusion of Mutations in the ASS1 Gene</em></strong></p><p>
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Kobayashi et al. (1993) found on sequence analysis no mutation in the ASS1 mRNA from 2 patients with adult-onset type II citrullinemia. They also reported RFLP analysis of a consanguineous family with type II citrullinemia in which 3 polymorphisms located within the ASS1 gene locus were examined. In spite of having consanguineous parents, the patient was not homozygous for the ASS1 gene haplotype. The RFLP analysis of 16 affected patients from consanguineous parents showed that 5 of 16 had the heterozygous pattern for 1 of the 3 DNA probes and that the frequency of the heterozygous haplotype was not different from the control frequency. These results suggested that the primary defect of type II citrullinemia was not within the ASS1 gene locus. </p><p><strong><em>Pathogenic Mutations in the SLC25A13 Gene</em></strong></p><p>
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In 18 adult patients with CTLN2 from consanguineous parents, Kobayashi et al. (1999) identified 5 distinct mutations (603859.0001-603859.0005) in the SLC25A13 gene, encoding citrin, and confirmed their causative role in the disease. The studies of adult-onset type II citrullinemia in Japanese were extended by Yasuda et al. (2000), who identified 2 novel mutations in the SLC25A13 gene (see, e.g., 603859). Diagnostic analysis for the 7 known mutations in 103 CTLN2 patients diagnosed by biochemical and enzymatic studies revealed that 102 patients had 1 or 2 of the 7 mutations and 93 patients were homozygotes or compound heterozygotes. Five of 22 patients from consanguineous unions were compound heterozygotes, suggesting a high frequency of the mutated genes. The frequency of homozygotes was calculated to be more than 1 in 20,000 from carrier detection (6 in 400 individuals tested) in the Japanese population. By Western blot analysis with antihuman citrin antibody, the authors detected no cross-reactive immune materials in the liver of CTLN2 patients with any of the 7 mutations. From these findings, Yasuda et al. (2000) hypothesized that CTLN2 is caused by a complete deletion of citrin, although this did not explain the mechanism of argininosuccinate synthetase deficiency. </p><p>In a 38-year-old Pakistani man living in Europe who had episodic confusion, elevated plasma ammonia and arginine levels, citrullinemia, normal glutamine, low serine levels, and fatal hyperammonemic encephalopathy, Fiermonte et al. (2008) identified homozygosity for a mutation at a highly conserved residue in the SLC25A13 gene (R588Q; 603859.0007). The authors noted that type II citrullinemia has rarely been reported outside of East Asia but must be considered in adults presenting with hyperammonemic encephalopathy, since the management is different from the management of classic urea-cycle defects (see 311250). </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Pathogenesis</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Saheki and Kobayashi (2002) concluded that citrin deficiency causes 2 different phenotypes, NICCD in neonates (605814) and CTLN2 in adults, through the additional effects of genetic or environmental modifiers. Since citrin and aralar (SLC25A12; 603667) are mitochondrial aspartate glutamate carriers, the various symptoms of NICCD and CTLN2 may be caused by defective aspartate export from the mitochondria to the cytosol and defects in the malate aspartate shuttle. </p><p>Komatsu et al. (2008) hypothesized that the hepatic steatosis observed in patients with CTLN2 may result from a compensatory upregulation of the malate-citrate shuttle, which increases citrate in the cytosol, resulting in increased acetyl-CoA and an overproduction of fatty acids in hepatocytes. </p>
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<h4>
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<span class="mim-font">
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<strong>Clinical Management</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Saheki et al. (2010) noted that conventional treatments for hyperammonemia and brain edema, such as glycerol, are harmful in patients with CTLN2 because use of carbohydrates can exacerbate hyperammonemia. The most effective treatment for this disorder is liver transplantation, although many patients can be managed by a low-carbohydrate/high-protein diet. Use of dietary arginine or sodium pyruvate may also be potentially therapeutic. </p>
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<h4>
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<span class="mim-font">
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<strong>Population Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Kobayashi et al. (1999) stated that the frequency of CTLN2 in Japan is approximately 1 in 100,000. </p><p>Yasuda et al. (2000) calculated the frequency of homozygotes of SLC25A13 mutations to be more than 1 in 20,000 from carrier detection (6 in 400 individuals tested) in the Japanese population. </p><p>Among 1,315 Japanese individuals tested, Yamaguchi et al. (2002) found that 18 were carriers of an SLC25A13 mutation; this provided an estimate of minimally 1 in 21,000 for homozygotes. They referred to 2 Chinese CTLN2 patients in Taiwan and a Vietnamese neonatal-onset type II citrullinemia (NICCD) patient in Australia who had the same SLC25A13 mutations as those identified in Japanese patients. </p><p>Lu et al. (2005) estimated the frequencies of SLC25A13 homozygotes to be 1 in 19,000 in Japan, 1 in 50,000 in Korea, and 1 in 17,000 in China. Specific mutations were identified in all Asian countries tested, with the most common mutations being a 4-bp deletion (603859.0001) and a splice site mutation (603859.0002). The frequencies of SLC25A13 homozygotes in China were calculated to be 1 in 9,200 to the south of the Yangtze River and 1 in 3,500,000 to the north of the Yangtze River. The findings were consistent with the historical boundary of the Yangtze River; modern Chinese are thought to derive from 2 distinct populations, 1 originating in the Yellow River valley and the other in the Yangtze River valley, during early Neolithic times (3,000 to 7,000 years ago). </p>
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<h4>
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<span class="mim-font">
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<strong>Animal Model</strong>
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</span>
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<span class="mim-text-font">
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<p>Slc25a13-knockout mice show reduced mitochondrial Asp transport, but have no apparent phenotype, likely due to increased hepatic activity of mitochondrial glycerol-3-phosphate dehydrogenase (GPD2; 138430), which can transport NADH reducing equivalents into mitochondria. Saheki et al. (2007) found that mice with a combined disruption of the Slc25a13 and Gpd2 genes had poor growth and developed citrullinemia, hyperammonemia, hypoglycemia, and fatty liver, all features of human citrin deficiency. An altered cytosolic NADH/NAD(+) ratio was closely associated with hyperammonemia. The data indicated that the more severe phenotype present in the Slc25a13/Gpd2 double-knockout mice represents a more accurate model of human citrin deficiency than Slc25a13-knockout mice. </p>
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</span>
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<div>
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<h4>
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<span class="mim-font">
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<strong>See Also:</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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Matsuda et al. (1979); Sase et al. (1985)
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</span>
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<br />
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<ol>
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<li>
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<p class="mim-text-font">
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Batshaw, M. L., Tuchman, M., Summar, M., Seminara, J., Members of the Urea Cycle Disorders Consortium.
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<strong>A longitudinal study of urea cycle disorders.</strong>
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Molec. Genet. Metab. 113: 127-130, 2014.
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[PubMed: 25135652]
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[Full Text: https://doi.org/10.1016/j.ymgme.2014.08.001]
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</li>
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<li>
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<p class="mim-text-font">
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Fiermonte, G., Soon, D., Chaudhuri, A., Paradies, E., Lee, P. J., Krywawych, S., Palmieri, F., Lachmann, R. H.
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<strong>An adult with type 2 citrullinemia presenting in Europe. (Letter)</strong>
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New Eng. J. Med. 358: 1408-1409, 2008.
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[PubMed: 18367750]
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[Full Text: https://doi.org/10.1056/NEJMc0707353]
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</li>
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<li>
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<p class="mim-text-font">
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Kobayashi, K., Shaheen, N., Kumashiro, R., Tanikawa, K., O'Brien, W. E., Beaudet, A. L., Saheki, T.
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<strong>A search for the primary abnormality in adult-onset type II citrullinemia.</strong>
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Am. J. Hum. Genet. 53: 1024-1030, 1993.
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[PubMed: 8105687]
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<li>
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<p class="mim-text-font">
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Kobayashi, K., Sinasac, D. S., Iijima, M., Boright, A. P., Begum, L., Lee, J. R., Yasuda, T., Ikeda, S., Hirano, R., Terazono, H., Crackower, M. A., Kondo, I., Tsui, L.-C., Scherer, S. W., Saheki, T.
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<strong>The gene mutated in adult-onset type II citrullinaemia encodes a putative mitochondrial carrier protein.</strong>
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Nature Genet. 22: 159-163, 1999.
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[PubMed: 10369257]
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[Full Text: https://doi.org/10.1038/9667]
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<p class="mim-text-font">
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Komatsu, M., Yazaki, M., Tanaka, N., Sano, K., Hashimoto, E., Takei, Y., Song, Y.-Z., Tanaka, E., Kiyosawa, K., Saheki, T., Aoyama, T., Kobayashi, K.
|
|
<strong>Citrin deficiency as a cause of chronic liver disorder mimicking non-alcoholic fatty liver disease.</strong>
|
|
J. Hepatol. 49: 810-820, 2008.
|
|
|
|
|
|
[PubMed: 18620775]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.jhep.2008.05.016]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Lu, Y. B., Kobayashi, K., Ushikai, M., Tabata, A., Iijima, M., Li, M. X., Lei, L., Kawabe, K., Taura, S., Yang, Y., Liu, T.-T., Chiang, S.-H., Hsiao, K.-J., Lau, Y.-L., Tsui, L.-C., Lee, D. H., Saheki, T.
|
|
<strong>Frequency and distribution in East Asia of 12 mutations identified in the SLC25A13 gene of Japanese patients with citrin deficiency.</strong>
|
|
J. Hum. Genet. 50: 338-346, 2005.
|
|
|
|
|
|
[PubMed: 16059747]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10038-005-0262-8]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matsuda, I., Anakura, M., Arashima, S., Saito, Y., Oka, Y.
|
|
<strong>Variant form of citrullinemia.</strong>
|
|
J. Pediat. 88: 824-826, 1976.
|
|
|
|
|
|
[PubMed: 1271146]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-3476(76)81123-7]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Matsuda, I., Arashima, S., Imanishi, Y., Yamamoto, J., Akaboshi, I., Shinozuka, S., Nagata, N.
|
|
<strong>Lysine intolerance in a variant form of citrullinemia.</strong>
|
|
Pediat. Res. 13: 1134-1136, 1979.
|
|
|
|
|
|
[PubMed: 503639]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1203/00006450-197910000-00010]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Saheki, T., Iijima, M., Li, M. X., Kobayashi, K., Horiuchi, M., Ushikai, M., Okumura, F., Meng, X. J., Inoue, I., Tajima, A., Moriyama, M., Eto, K., Kadowaki, T., Sinasac, D. S., Tsui, L.-C., Tsuji, M., Okano, A., Kobayashi, T.
|
|
<strong>Citrin/mitochondrial glycerol-3-phosphate dehydrogenase double knock-out mice recapitulate features of human citrin deficiency.</strong>
|
|
J. Biol. Chem. 282: 25041-25052, 2007.
|
|
|
|
|
|
[PubMed: 17591776]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1074/jbc.M702031200]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Saheki, T., Inoue, K., Tushima, A., Mutoh, K., Kobayashi, K.
|
|
<strong>Citrin deficiency and current treatment concepts.</strong>
|
|
Molec. Genet. Metab. 100 (Suppl. 1): S59-S64, 2010.
|
|
|
|
|
|
[PubMed: 20233664]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2010.02.014]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Saheki, T., Kobayashi, K.
|
|
<strong>Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD).</strong>
|
|
J. Hum. Genet. 47: 333-341, 2002.
|
|
|
|
|
|
[PubMed: 12111366]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s100380200046]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sase, M., Kobayashi, K., Imamura, Y., Saheki, T., Nakano, K., Miura, S., Mori, M.
|
|
<strong>Level of translatable messenger RNA coding for argininosuccinate synthetase in the liver of the patients with quantitative-type citrullinemia.</strong>
|
|
Hum. Genet. 69: 130-134, 1985.
|
|
|
|
|
|
[PubMed: 3972414]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/BF00293282]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Scott-Emuakpor, A., Higgins, J. V., Kohrman, A. F.
|
|
<strong>Citrullinemia: a new case, with implications concerning adaptation to defective urea synthesis.</strong>
|
|
Pediat. Res. 6: 626-633, 1972.
|
|
|
|
|
|
[PubMed: 5057291]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Walser, M.
|
|
<strong>Urea cycle disorders and other hereditary hyperammonemic syndromes. In: Stanbury, J. B.; Wyngaarden, J. B.; Fredrickson, D. S.; Goldstein, J. L.; Brown, M. S. (eds.): The Metabolic Basis of Inherited Disease. (5th ed.)</strong>
|
|
New York: McGraw-Hill (pub.) 1983. Pp. 402-438.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
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Yamaguchi, N., Kobayashi, K., Yasuda, T., Nishi, I., Iijima, M., Nakagawa, M., Osame, M., Kondo, I., Saheki, T.
|
|
<strong>Screening of SLC25A13 mutations in early and late onset patients with citrin deficiency and in the Japanese population: identification of two novel mutations and establishment of multiple DNA diagnosis methods for nine mutations.</strong>
|
|
Hum. Mutat. 19: 122-130, 2002.
|
|
|
|
|
|
[PubMed: 11793471]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1002/humu.10022]
|
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</p>
|
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</li>
|
|
|
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<li>
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<p class="mim-text-font">
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Yasuda, T., Yamaguchi, N., Kobayashi, K., Nishi, I., Horinouchi, H., Jalil, M. A., Li, M. X., Ushikai, M., Iijima, M., Kondo, I., Saheki, T.
|
|
<strong>Identification of two novel mutations in the SLC25A13 gene and detection of seven mutations in 102 patients with adult-onset type II citrullinemia.</strong>
|
|
Hum. Genet. 107: 537-545, 2000.
|
|
|
|
|
|
[PubMed: 11153906]
|
|
|
|
|
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[Full Text: https://doi.org/10.1007/s004390000430]
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