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Entry
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- #605814 - CITRULLINEMIA, TYPE II, NEONATAL-ONSET
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- OMIM
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<p>
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<span class="h4">#605814</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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<a href="/clinicalSynopsis/605814"><strong>Clinical Synopsis</strong></a>
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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="#clinicalManagement">Clinical Management</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="#populationGenetics">Population Genetics</a>
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<a href="#nomenclature">Nomenclature</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div style="display: table-cell;">External Links</div>
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</h4>
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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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><a href="https://clinicaltrials.gov/search?cond=CITRULLINEMIA, TYPE II, NEONATAL-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=19529&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/1648" 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="#mimMedlinePlusGeneticsFold" id="mimMedlinePlusGeneticsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Consumer-friendly information about the effects of genetic variation on human health."><span id="mimMedlinePlusGeneticsToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>MedlinePlus Genetics</div>
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<div id="mimMedlinePlusGeneticsFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://medlineplus.gov/genetics/condition/citrullinemia" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">Citrullinemia </a></div><div style="margin-left: 0.5em;"><a href="https://medlineplus.gov/genetics/gene/slc25a13" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">SLC25A13 gene </a></div>
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</div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=605814[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="#mimNewbornScreeningFold" id="mimNewbornScreeningToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Information and resources for newborn screening and genetics."><span id="mimNewbornScreeningToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Newborn Screening</div>
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<div id="mimNewbornScreeningFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.acmg.net/PDFLibrary/Citrullinemia.pdf" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Newborn Screening', 'domain': 'www.acmg.net'})">ACMG ACT Sheet</a></div><div style="margin-left: 0.5em;"><a href="https://www.acmg.net/PDFLibrary/Citrulline-Algorithm.pdf" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Newborn Screening', 'domain': 'www.acmg.net'})">ACMG Algorithm</a></div>
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</div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=247598" 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 panel-default" style="margin-top: 0px; border-radius: 0px">
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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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<div><a href="https://www.alliancegenome.org/disease/DOID:0070341" 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/605814" 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:0070341" 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>
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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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</div>
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<div>
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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> 717155003<br />
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<strong>ORPHA:</strong> 247598<br />
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<strong>DO:</strong> 0070341<br />
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">ICD+</a>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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605814
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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, NEONATAL-ONSET
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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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</p>
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<div>
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<h4>
|
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<span class="mim-font">
|
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CITRULLINEMIA, TYPE II, NEONATAL-ONSET, WITH OR WITHOUT FAILURE TO THRIVE AND DYSLIPIDEMIA<br />
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CHOLESTASIS, NEONATAL INTRAHEPATIC, CAUSED BY CITRIN DEFICIENCY; NICCD
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</span>
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</h4>
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<div>
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<br />
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<a id="phenotypeMap" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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<strong>Phenotype-Gene Relationships</strong>
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</span>
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</h4>
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<div>
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<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/7/434?start=-3&limit=10&highlight=434">
|
|
7q21.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Citrullinemia, type II, neonatal-onset
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/605814"> 605814 </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">
|
|
SLC25A13
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603859"> 603859 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/605814" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
|
|
<a href="/phenotypicSeries/PS215700" class="btn btn-info" role="button"> Phenotypic Series </a>
|
|
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/605814" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/605814" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> GROWTH </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Other </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Failure to thrive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/432788009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">432788009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/54840006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">54840006</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0015544&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015544</a>, <a href="https://bioportal.bioontology.org/search?q=C2315100&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2315100</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span><br /> -
|
|
Poor growth <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837385&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837385</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001510</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001510</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ABDOMEN </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Liver </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Intrahepatic cholestasis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/4637005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">4637005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0008372&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0008372</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001406" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001406</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001406" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001406</a>]</span><br /> -
|
|
Elevated bilirubin (bilirubinemia) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853946&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853946</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/26165005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">26165005</a>]</span><br /> -
|
|
Cirrhosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/19943007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">19943007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K74.60" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K74.60</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0023890&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023890</a>, <a href="https://bioportal.bioontology.org/search?q=C1623038&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1623038</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001394" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001394</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001394" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001394</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEMATOLOGY </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Echinocytosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/250248000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">250248000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0427484&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0427484</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> LABORATORY ABNORMALITIES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Elevated plasma citrulline (citrullinemia) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853943&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853943</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011966" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011966</a>]</span><br /> -
|
|
Elevated plasma methionine (methioninemia) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853944&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853944</a>]</span><br /> -
|
|
Elevated plasma galactose (galactosemia) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853945&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853945</a>]</span><br /> -
|
|
Elevated bilirubin (bilirubinemia) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853946&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853946</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/26165005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">26165005</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 cholesterol <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3276464&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3276464</a>]</span><br /> -
|
|
Decreased HDL cholesterol <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151691&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151691</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003233" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003233</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003233" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003233</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">
|
|
|
|
- Most have resolution of symptoms between 6 and 12 months<br /> -
|
|
Some patients may develop concurrent failure to thrive and dyslipidemia<br /> -
|
|
Natural aversion to carbohydrates and favoring of protein<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
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<strong> MOLECULAR BASIS </strong>
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- Caused by mutation in the solute carrier family 25 (mitochondrial carrier, citrin), member 13 gene (SLC25A13, <a href="/entry/603859#0001">603859.0001</a>)<br />
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Citrullinemia
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- <a href="/phenotypicSeries/PS215700">PS215700</a>
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- 3 Entries
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<a href="/geneMap/7/434?start=-3&limit=10&highlight=434"> 7q21.3 </a>
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<a href="/entry/603471"> Citrullinemia, adult-onset type II </a>
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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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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<a href="/entry/603471"> 603471 </a>
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<a href="/entry/603859"> SLC25A13 </a>
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<a href="/entry/603859"> 603859 </a>
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<a href="/geneMap/7/434?start=-3&limit=10&highlight=434"> 7q21.3 </a>
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<a href="/entry/605814"> Citrullinemia, type II, neonatal-onset </a>
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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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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<a href="/entry/605814"> 605814 </a>
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<a href="/entry/603859"> SLC25A13 </a>
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<a href="/entry/603859"> 603859 </a>
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<a href="/geneMap/9/577?start=-3&limit=10&highlight=577"> 9q34.11 </a>
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<span class="mim-font">
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<a href="/entry/215700"> Citrullinemia </a>
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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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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<a href="/entry/215700"> 215700 </a>
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<a href="/entry/603470"> ASS1 </a>
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<a href="/entry/603470"> 603470 </a>
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because neonatal-onset type II citrullinemia, also known as neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), is caused by homozygous or compound heterozygous mutation in the SLC25A13 gene (<a href="/entry/603859">603859</a>).</p><p>Adult-onset type II citrullinemia (<a href="/entry/603471">603471</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>Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive metabolic disorder characterized by poor growth, intrahepatic cholestasis, and increased serum citrulline. Most patients show spontaneous improvement by 1 year of age. However, some patients may have a progressive course with continued failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), and some may develop chronic or fatal liver disease (summary by <a href="#8" class="mim-tip-reference" title="Song, Y.-Z., Deng, M., Chen, F.-P., Wen, F., Guo, L., Cao, S.-L., Gong, J., Xu, H., Jiang, G.-Y., Zhong, L., Kobayashi, K., Saheki, T., Wang, Z.-N. <strong>Genotypic and phenotypic features of citrin deficiency: five-year experience in a Chinese pediatric center.</strong> Int. J. Molec. Med. 28: 33-40, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21424115/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21424115</a>] [<a href="https://doi.org/10.3892/ijmm.2011.653" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21424115">Song et al., 2011</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21424115" 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="#5" class="mim-tip-reference" title="Ohura, T., Kobayashi, K., Tazawa, Y., Nishi, I., Abukawa, D., Sakamoto, O., Iinuma, K., Saheki, T. <strong>Neonatal presentation of adult-onset type II citrullinemia.</strong> Hum. Genet. 108: 87-90, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11281457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11281457</a>] [<a href="https://doi.org/10.1007/s004390000448" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11281457">Ohura et al. (2001)</a> reported 3 neonates who presented with intrahepatic cholestasis associated with hypermethioninemia or hypergalactosemia detected by a neonatal mass screening. One infant was of average gestational age and had a methionine level of 134 micromol/l. His younger brother, also born at term, manifested liver dysfunction by day 3 of life. The other infant had elevated galactose levels. Plasma amino acid analysis showed significant elevation of citrulline and methionine in all 3 patients. The concentrations of threonine, tyrosine, lysine, and arginine were also 2 to 4 times higher than control levels. Organic acids in 1 patient showed elevation of hydroxyphenyllactic acid and hydroxyphenylpyruvic acid. Succinylacetone was not detected in any patients. Without specific treatment other than feeding with formula containing medium-chain triglycerides or lactose-free formula, all 3 patients had favorable clinical courses. Amino acid profiles were abnormal for the first couple of months, but resolved entirely by 12 months of age. Cholestasis improved by 3 months of age. On follow-up for 18 months to 8 years, all patients were alive and showed no developmental delay or neurologic abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11281457" 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="#13" class="mim-tip-reference" title="Tomomasa, T., Kobayashi, K., Kaneko, H., Shimura, H., Fukusato, T., Tabata, M., Inoue, Y., Ohwada, S., Kasahara, M., Morishita, Y., Kimura, M., Saheki, T., Morikawa, A. <strong>Possible clinical and histologic manifestations of adult-onset type II citrullinemia in early infancy.</strong> J. Pediat. 138: 741-743, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11343053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11343053</a>] [<a href="https://doi.org/10.1067/mpd.2001.113361" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11343053">Tomomasa et al. (2001)</a> described 2 patients with type II citrullinemia who developed transient hypoproteinemia and jaundice in early infancy. Liver histology showed markedly fatty changes and fibrosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11343053" 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="#12" class="mim-tip-reference" title="Tazawa, Y., Kobayashi, K., Ohura, T., Abukawa, D., Nishinomiya, F., Hosoda, Y., Yamashita, M., Nagata, I., Kono, Y., Yasuda, T., Yamaguchi, N., Saheki, T. <strong>Infantile cholestatic jaundice associated with adult-onset type II citrullinemia.</strong> J. Pediat. 138: 735-740, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11343052/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11343052</a>] [<a href="https://doi.org/10.1067/mpd.2001.113264" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11343052">Tazawa et al. (2001)</a> described 3 children with neonatal-onset of type II citrullinemia who presented between 1 and 5 months of age with cholestatic jaundice. Liver histology showed fatty tissue without evidence of giant cell hepatitis, the usual finding in most forms of transient neonatal jaundice. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11343052" 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="#11" class="mim-tip-reference" title="Tamamori, A., Okano, Y., Ozaki, H., Fujimoto, A., Kajiwara, M., Fukuda, K., Kobayashi, K., Saheki, T., Tagami, Y., Yamano, T. <strong>Neonatal intrahepatic cholestasis caused by citrin deficiency: severe hepatic dysfunction in an infant requiring liver transplantation.</strong> Europ. J. Pediat. 161: 609-613, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12424587/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12424587</a>] [<a href="https://doi.org/10.1007/s00431-002-1045-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12424587">Tamamori et al. (2002)</a> reported 5 patients with neonatal intrahepatic cholestasis caused by citrin deficiency and confirmed by mutation analysis. Four of the patients showed a typical disease course, with spontaneous remission between 5 and 7 months of age. All patients had very high serum levels of alpha-fetoprotein (AFP; <a href="/entry/104150">104150</a>), which the authors attributed to premature hepatocytes and hepatic damage or regeneration. One patient had an unusual disease course with a worsening of liver function at age 6 months, ultimately requiring a living-related liver transplant at 10 months of age. She had normal growth and mental development at age 3 years. The patient was compound heterozygous for 2 previously reported mutations in the SLC25A13 gene (<a href="/entry/603859#0001">603859.0001</a>; <a href="/entry/603859#0002">603859.0002</a>). <a href="#11" class="mim-tip-reference" title="Tamamori, A., Okano, Y., Ozaki, H., Fujimoto, A., Kajiwara, M., Fukuda, K., Kobayashi, K., Saheki, T., Tagami, Y., Yamano, T. <strong>Neonatal intrahepatic cholestasis caused by citrin deficiency: severe hepatic dysfunction in an infant requiring liver transplantation.</strong> Europ. J. Pediat. 161: 609-613, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12424587/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12424587</a>] [<a href="https://doi.org/10.1007/s00431-002-1045-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12424587">Tamamori et al. (2002)</a> noted that the same genotype had been identified in a patient with the usual course of spontaneous remission (<a href="#5" class="mim-tip-reference" title="Ohura, T., Kobayashi, K., Tazawa, Y., Nishi, I., Abukawa, D., Sakamoto, O., Iinuma, K., Saheki, T. <strong>Neonatal presentation of adult-onset type II citrullinemia.</strong> Hum. Genet. 108: 87-90, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11281457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11281457</a>] [<a href="https://doi.org/10.1007/s004390000448" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11281457">Ohura et al., 2001</a>), suggesting that the severe phenotype was not due to the genotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12424587+11281457" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Naito, E., Ito, M., Matsuura, S., Yokota, I., Saijo, T., Ogawa, Y., Kitamura, S., Kobayashi, K., Saheki, T., Nishimura, Y., Sakura, N., Kuroda, Y. <strong>Type II citrullinaemia (citrin deficiency) in a neonate with hypergalactosaemia detected by mass screening.</strong> J. Inherit. Metab. Dis. 25: 71-76, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11999983/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11999983</a>] [<a href="https://doi.org/10.1023/a:1015198103395" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11999983">Naito et al. (2002)</a> described an infant who presented with neonatal hepatitis in association with hypergalactosemia detected by neonatal mass screening. DNA analysis of the SLC25A13 gene identified homozygosity for an intron 11 splice site mutation (<a href="/entry/603859#0002">603859.0002</a>). <a href="#4" class="mim-tip-reference" title="Naito, E., Ito, M., Matsuura, S., Yokota, I., Saijo, T., Ogawa, Y., Kitamura, S., Kobayashi, K., Saheki, T., Nishimura, Y., Sakura, N., Kuroda, Y. <strong>Type II citrullinaemia (citrin deficiency) in a neonate with hypergalactosaemia detected by mass screening.</strong> J. Inherit. Metab. Dis. 25: 71-76, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11999983/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11999983</a>] [<a href="https://doi.org/10.1023/a:1015198103395" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11999983">Naito et al. (2002)</a> concluded that mutations in the SLC25A13 gene should be suspected in neonatal patients with hypergalactosemia of unknown cause. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11999983" 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><p><strong><em>Clinical Variability</em></strong></p><p>
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Most patients with NICCD show clinical improvement between 6 and 12 months of age, and enter what is termed the 'apparently healthy period.' However, some of these patients may develop cirrhosis or severe infections, or may later develop symptoms of adult-onset citrin deficiency (<a href="/entry/603471">603471</a>). Descriptions of post-NICCD presentations before onset of CTLN2 is limited. <a href="#9" class="mim-tip-reference" title="Song, Y.-Z., Guo, L., Yang, Y.-L., Han, L.-S., Kobayashi, K., Saheki, T. Failure to thrive and dyslipidemia caused by citrin deficiency. <strong>a novel clinical phenotype.</strong> Chin. J. Contemp. Pediat. 11: 328-332, 2009."None>Song et al. (2009)</a> described a Chinese child with citrin deficiency who had a novel phenotype consisting of continued failure to thrive and dyslipidemia due to citrin deficiency (FTTDCD) after age 1 year.</p><p><a href="#8" class="mim-tip-reference" title="Song, Y.-Z., Deng, M., Chen, F.-P., Wen, F., Guo, L., Cao, S.-L., Gong, J., Xu, H., Jiang, G.-Y., Zhong, L., Kobayashi, K., Saheki, T., Wang, Z.-N. <strong>Genotypic and phenotypic features of citrin deficiency: five-year experience in a Chinese pediatric center.</strong> Int. J. Molec. Med. 28: 33-40, 2011.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21424115/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21424115</a>] [<a href="https://doi.org/10.3892/ijmm.2011.653" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="21424115">Song et al. (2011)</a> evaluated the phenotype of 51 Chinese children with genetically confirmed citrin deficiency, and found that 9 of 34 post-NICCD cases over 1 year of age had concurrent FTTDCD. These patients had higher total bile acid levels, suggesting increased intraphepatic cholestasis. Seven of the 51 were found to have echinocytosis, which was associated with more severe biochemical abnormalities. Delayed hepatic discharge and bile duct/bowel visualization were common scintigraphic findings in the whole cohort. The findings expanded the phenotypic spectrum of citrin deficiency in children. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21424115" 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 a retrospective investigation of 21 Chinese NICCD patients, <a href="#10" class="mim-tip-reference" title="Song, Y.-Z., Wen, F., Chen, F.-P., Kobayashi, K., Saheki, T. <strong>Neonatal intraphepatic cholestasis caused by citrin deficiency: efficacy of therapeutic formulas and update of clinical outcomes.</strong> Jpn. J. Inherit. Metab. Dis. 26: 57-69, 2010."None>Song et al. (2010)</a> found that those treated with therapeutic formulas had catch-up growth and biochemical improvement. The authors concluded that breast milk, which is high in carbohydrates, is not a suitable diet for such patients. Dietary macronutrient formula types with higher protein levels are good sources of food. Vitamin D supplementation may help alleviate neuropsychiatric disturbances.</p><p>In a review, <a href="#6" class="mim-tip-reference" title="Okano, Y., Ohura, T., Sakamoto, O., Inui, A. <strong>Current treatment for citrin deficiency during NICCD and adaptation/compensation stages: strategy to prevent CTLN2.</strong> Molec. Genet. Metab. 127: 175-183, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31255436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31255436</a>] [<a href="https://doi.org/10.1016/j.ymgme.2019.06.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31255436">Okano et al. (2019)</a> stated that treatment of infants with NICCD with lactose-free formula supplemented with MCT oil is an appropriate dietary intervention. Supplementation with lipid soluble vitamins, particularly vitamin K, may be helpful in the setting of cholestasis. <a href="#6" class="mim-tip-reference" title="Okano, Y., Ohura, T., Sakamoto, O., Inui, A. <strong>Current treatment for citrin deficiency during NICCD and adaptation/compensation stages: strategy to prevent CTLN2.</strong> Molec. Genet. Metab. 127: 175-183, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31255436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31255436</a>] [<a href="https://doi.org/10.1016/j.ymgme.2019.06.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31255436">Okano et al. (2019)</a> also noted that intravenous treatment with a high glucose-containing fluid may precipitate liver failure. Dietary intake in childhood and beyond should be lower in carbohydrates and higher in fat and protein compared to a standard diet. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31255436" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#2" class="mim-tip-reference" title="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 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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<p>In 3 neonates with neonatal-onset type II citrullinemia, <a href="#5" class="mim-tip-reference" title="Ohura, T., Kobayashi, K., Tazawa, Y., Nishi, I., Abukawa, D., Sakamoto, O., Iinuma, K., Saheki, T. <strong>Neonatal presentation of adult-onset type II citrullinemia.</strong> Hum. Genet. 108: 87-90, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11281457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11281457</a>] [<a href="https://doi.org/10.1007/s004390000448" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11281457">Ohura et al. (2001)</a> identified mutations in the SLC25A13 gene. The sibs were homozygous for an IVS11+1G-A mutation (<a href="/entry/603859#0002">603859.0002</a>), and the third child was a compound heterozygote for the same mutation and the 851del4 mutation (<a href="/entry/603859#0001">603859.0001</a>). <a href="#5" class="mim-tip-reference" title="Ohura, T., Kobayashi, K., Tazawa, Y., Nishi, I., Abukawa, D., Sakamoto, O., Iinuma, K., Saheki, T. <strong>Neonatal presentation of adult-onset type II citrullinemia.</strong> Hum. Genet. 108: 87-90, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11281457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11281457</a>] [<a href="https://doi.org/10.1007/s004390000448" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11281457">Ohura et al. (2001)</a> concluded that there may be a variety of liver diseases related to mutations in the SLC25A13 gene in children. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11281457" 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="#13" class="mim-tip-reference" title="Tomomasa, T., Kobayashi, K., Kaneko, H., Shimura, H., Fukusato, T., Tabata, M., Inoue, Y., Ohwada, S., Kasahara, M., Morishita, Y., Kimura, M., Saheki, T., Morikawa, A. <strong>Possible clinical and histologic manifestations of adult-onset type II citrullinemia in early infancy.</strong> J. Pediat. 138: 741-743, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11343053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11343053</a>] [<a href="https://doi.org/10.1067/mpd.2001.113361" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11343053">Tomomasa et al. (2001)</a> found that the patients they studied were homozygous for the IVS11+1G-A mutation in the SLC25A13 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11343053" 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="#12" class="mim-tip-reference" title="Tazawa, Y., Kobayashi, K., Ohura, T., Abukawa, D., Nishinomiya, F., Hosoda, Y., Yamashita, M., Nagata, I., Kono, Y., Yasuda, T., Yamaguchi, N., Saheki, T. <strong>Infantile cholestatic jaundice associated with adult-onset type II citrullinemia.</strong> J. Pediat. 138: 735-740, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11343052/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11343052</a>] [<a href="https://doi.org/10.1067/mpd.2001.113264" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11343052">Tazawa et al. (2001)</a> also identified mutations in the SLC25A13 gene in 3 children with neonatal-onset type II citrullinemia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11343052" 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="#7" 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 and CTLN2 in adults (<a href="/entry/603471">603471</a>), 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>
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<p>Type II citrullinemia, both neonatal and adult onset, appears to be found almost exclusively in Japan.</p><p><a href="#15" 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><a href="#14" 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> referred to 2 Chinese CTLN2 patients in Taiwan and a Vietnamese NICCD patient in Australia who had the same SLC25A13 mutations as those identified in Japanese patients. Among 1,315 Japanese individuals tested, 18 were found to be carriers of an SLC25A13 mutation; this provided an estimate of minimally 1 in 21,000 for homozygotes. <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="#3" 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><a href="#14" 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> designated the neonatal/infantile form of type II citrullinemia as NICCD (neonatal intrahepatic cholestasis caused by citrin deficiency). <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>
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<strong>REFERENCES</strong>
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[<a href="https://doi.org/10.1016/j.ymgme.2014.08.001" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/9667" target="_blank">Full Text</a>]
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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.
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<strong>Frequency and distribution in East Asia of 12 mutations identified in the SLC25A13 gene of Japanese patients with citrin deficiency.</strong>
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J. Hum. Genet. 50: 338-346, 2005.
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[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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Naito, E., Ito, M., Matsuura, S., Yokota, I., Saijo, T., Ogawa, Y., Kitamura, S., Kobayashi, K., Saheki, T., Nishimura, Y., Sakura, N., Kuroda, Y.
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<strong>Type II citrullinaemia (citrin deficiency) in a neonate with hypergalactosaemia detected by mass screening.</strong>
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J. Inherit. Metab. Dis. 25: 71-76, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11999983/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11999983</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11999983" 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/10.1023/a:1015198103395" target="_blank">Full Text</a>]
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<a id="Ohura2001" class="mim-anchor"></a>
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Ohura, T., Kobayashi, K., Tazawa, Y., Nishi, I., Abukawa, D., Sakamoto, O., Iinuma, K., Saheki, T.
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<strong>Neonatal presentation of adult-onset type II citrullinemia.</strong>
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Hum. Genet. 108: 87-90, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11281457/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11281457</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11281457" 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/s004390000448" target="_blank">Full Text</a>]
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Okano, Y., Ohura, T., Sakamoto, O., Inui, A.
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<strong>Current treatment for citrin deficiency during NICCD and adaptation/compensation stages: strategy to prevent CTLN2.</strong>
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Molec. Genet. Metab. 127: 175-183, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31255436/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31255436</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31255436" 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.2019.06.004" target="_blank">Full Text</a>]
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<a id="Saheki2002" class="mim-anchor"></a>
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<div class="">
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Saheki, T., Kobayashi, K.
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<strong>Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD).</strong>
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J. Hum. Genet. 47: 333-341, 2002.
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[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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<a id="Song2011" class="mim-anchor"></a>
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Song, Y.-Z., Deng, M., Chen, F.-P., Wen, F., Guo, L., Cao, S.-L., Gong, J., Xu, H., Jiang, G.-Y., Zhong, L., Kobayashi, K., Saheki, T., Wang, Z.-N.
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<strong>Genotypic and phenotypic features of citrin deficiency: five-year experience in a Chinese pediatric center.</strong>
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Int. J. Molec. Med. 28: 33-40, 2011.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21424115/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21424115</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21424115" 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/10.3892/ijmm.2011.653" target="_blank">Full Text</a>]
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<a id="Song2009" class="mim-anchor"></a>
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Song, Y.-Z., Guo, L., Yang, Y.-L., Han, L.-S., Kobayashi, K., Saheki, T. Failure to thrive and dyslipidemia caused by citrin deficiency.
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Chin. J. Contemp. Pediat. 11: 328-332, 2009.
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<a id="Song2010" class="mim-anchor"></a>
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<div class="">
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Song, Y.-Z., Wen, F., Chen, F.-P., Kobayashi, K., Saheki, T.
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<strong>Neonatal intraphepatic cholestasis caused by citrin deficiency: efficacy of therapeutic formulas and update of clinical outcomes.</strong>
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Jpn. J. Inherit. Metab. Dis. 26: 57-69, 2010.
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<a id="Tamamori2002" class="mim-anchor"></a>
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Tamamori, A., Okano, Y., Ozaki, H., Fujimoto, A., Kajiwara, M., Fukuda, K., Kobayashi, K., Saheki, T., Tagami, Y., Yamano, T.
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<strong>Neonatal intrahepatic cholestasis caused by citrin deficiency: severe hepatic dysfunction in an infant requiring liver transplantation.</strong>
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Europ. J. Pediat. 161: 609-613, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12424587/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12424587</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12424587" 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/s00431-002-1045-2" target="_blank">Full Text</a>]
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<a id="Tazawa2001" class="mim-anchor"></a>
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Tazawa, Y., Kobayashi, K., Ohura, T., Abukawa, D., Nishinomiya, F., Hosoda, Y., Yamashita, M., Nagata, I., Kono, Y., Yasuda, T., Yamaguchi, N., Saheki, T.
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<strong>Infantile cholestatic jaundice associated with adult-onset type II citrullinemia.</strong>
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J. Pediat. 138: 735-740, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11343052/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11343052</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11343052" 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/10.1067/mpd.2001.113264" target="_blank">Full Text</a>]
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<a id="Tomomasa2001" class="mim-anchor"></a>
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Tomomasa, T., Kobayashi, K., Kaneko, H., Shimura, H., Fukusato, T., Tabata, M., Inoue, Y., Ohwada, S., Kasahara, M., Morishita, Y., Kimura, M., Saheki, T., Morikawa, A.
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<strong>Possible clinical and histologic manifestations of adult-onset type II citrullinemia in early infancy.</strong>
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J. Pediat. 138: 741-743, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11343053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11343053</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11343053" 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/10.1067/mpd.2001.113361" target="_blank">Full Text</a>]
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<a id="Yamaguchi2002" class="mim-anchor"></a>
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Yamaguchi, N., Kobayashi, K., Yasuda, T., Nishi, I., Iijima, M., Nakagawa, M., Osame, M., Kondo, I., Saheki, T.
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<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>
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Hum. Mutat. 19: 122-130, 2002.
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[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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<a id="Yasuda2000" class="mim-anchor"></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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Hilary J. Vernon - updated : 04/21/2020
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Ada Hamosh - updated : 01/08/2015<br>Cassandra L. Kniffin - updated : 7/19/2011<br>Cassandra L. Kniffin - updated : 11/8/2005<br>Cassandra L. Kniffin - updated : 8/11/2004<br>Cassandra L. Kniffin - reorganized : 8/15/2002<br>Victor A. McKusick - updated : 2/26/2002<br>Deborah L. Stone - updated : 11/21/2001
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Creation Date:
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Ada Hamosh : 4/3/2001
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carol : 04/21/2020
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carol : 09/12/2017<br>carol : 10/05/2016<br>alopez : 01/08/2015<br>wwang : 7/29/2011<br>ckniffin : 7/19/2011<br>wwang : 3/31/2006<br>wwang : 11/16/2005<br>wwang : 11/16/2005<br>ckniffin : 11/8/2005<br>carol : 8/11/2004<br>ckniffin : 8/11/2004<br>carol : 8/15/2002<br>ckniffin : 8/15/2002<br>ckniffin : 8/15/2002<br>carol : 2/26/2002<br>carol : 11/21/2001<br>carol : 11/21/2001<br>carol : 11/5/2001<br>carol : 4/3/2001<br>carol : 4/3/2001
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<span class="mim-font">
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<strong>#</strong> 605814
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CITRULLINEMIA, TYPE II, NEONATAL-ONSET
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<em>Alternative titles; symbols</em>
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CITRULLINEMIA, TYPE II, NEONATAL-ONSET, WITH OR WITHOUT FAILURE TO THRIVE AND DYSLIPIDEMIA<br />
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CHOLESTASIS, NEONATAL INTRAHEPATIC, CAUSED BY CITRIN DEFICIENCY; NICCD
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<strong>SNOMEDCT:</strong> 717155003;
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<strong>ORPHA:</strong> 247598;
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<strong>DO:</strong> 0070341;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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<span class="mim-font">
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7q21.3
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<span class="mim-font">
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Citrullinemia, type II, neonatal-onset
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<span class="mim-font">
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605814
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Autosomal recessive
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3
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SLC25A13
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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 neonatal-onset type II citrullinemia, also known as neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), is caused by homozygous or compound heterozygous mutation in the SLC25A13 gene (603859).</p><p>Adult-onset type II citrullinemia (603471) 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>Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive metabolic disorder characterized by poor growth, intrahepatic cholestasis, and increased serum citrulline. Most patients show spontaneous improvement by 1 year of age. However, some patients may have a progressive course with continued failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), and some may develop chronic or fatal liver disease (summary by Song et al., 2011). </p>
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<strong>Clinical Features</strong>
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<p>Ohura et al. (2001) reported 3 neonates who presented with intrahepatic cholestasis associated with hypermethioninemia or hypergalactosemia detected by a neonatal mass screening. One infant was of average gestational age and had a methionine level of 134 micromol/l. His younger brother, also born at term, manifested liver dysfunction by day 3 of life. The other infant had elevated galactose levels. Plasma amino acid analysis showed significant elevation of citrulline and methionine in all 3 patients. The concentrations of threonine, tyrosine, lysine, and arginine were also 2 to 4 times higher than control levels. Organic acids in 1 patient showed elevation of hydroxyphenyllactic acid and hydroxyphenylpyruvic acid. Succinylacetone was not detected in any patients. Without specific treatment other than feeding with formula containing medium-chain triglycerides or lactose-free formula, all 3 patients had favorable clinical courses. Amino acid profiles were abnormal for the first couple of months, but resolved entirely by 12 months of age. Cholestasis improved by 3 months of age. On follow-up for 18 months to 8 years, all patients were alive and showed no developmental delay or neurologic abnormalities. </p><p>Tomomasa et al. (2001) described 2 patients with type II citrullinemia who developed transient hypoproteinemia and jaundice in early infancy. Liver histology showed markedly fatty changes and fibrosis. </p><p>Tazawa et al. (2001) described 3 children with neonatal-onset of type II citrullinemia who presented between 1 and 5 months of age with cholestatic jaundice. Liver histology showed fatty tissue without evidence of giant cell hepatitis, the usual finding in most forms of transient neonatal jaundice. </p><p>Tamamori et al. (2002) reported 5 patients with neonatal intrahepatic cholestasis caused by citrin deficiency and confirmed by mutation analysis. Four of the patients showed a typical disease course, with spontaneous remission between 5 and 7 months of age. All patients had very high serum levels of alpha-fetoprotein (AFP; 104150), which the authors attributed to premature hepatocytes and hepatic damage or regeneration. One patient had an unusual disease course with a worsening of liver function at age 6 months, ultimately requiring a living-related liver transplant at 10 months of age. She had normal growth and mental development at age 3 years. The patient was compound heterozygous for 2 previously reported mutations in the SLC25A13 gene (603859.0001; 603859.0002). Tamamori et al. (2002) noted that the same genotype had been identified in a patient with the usual course of spontaneous remission (Ohura et al., 2001), suggesting that the severe phenotype was not due to the genotype. </p><p>Naito et al. (2002) described an infant who presented with neonatal hepatitis in association with hypergalactosemia detected by neonatal mass screening. DNA analysis of the SLC25A13 gene identified homozygosity for an intron 11 splice site mutation (603859.0002). Naito et al. (2002) concluded that mutations in the SLC25A13 gene should be suspected in neonatal patients with hypergalactosemia of unknown cause. </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><p><strong><em>Clinical Variability</em></strong></p><p>
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Most patients with NICCD show clinical improvement between 6 and 12 months of age, and enter what is termed the 'apparently healthy period.' However, some of these patients may develop cirrhosis or severe infections, or may later develop symptoms of adult-onset citrin deficiency (603471). Descriptions of post-NICCD presentations before onset of CTLN2 is limited. Song et al. (2009) described a Chinese child with citrin deficiency who had a novel phenotype consisting of continued failure to thrive and dyslipidemia due to citrin deficiency (FTTDCD) after age 1 year.</p><p>Song et al. (2011) evaluated the phenotype of 51 Chinese children with genetically confirmed citrin deficiency, and found that 9 of 34 post-NICCD cases over 1 year of age had concurrent FTTDCD. These patients had higher total bile acid levels, suggesting increased intraphepatic cholestasis. Seven of the 51 were found to have echinocytosis, which was associated with more severe biochemical abnormalities. Delayed hepatic discharge and bile duct/bowel visualization were common scintigraphic findings in the whole cohort. The findings expanded the phenotypic spectrum of citrin deficiency in children. </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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<p>In a retrospective investigation of 21 Chinese NICCD patients, Song et al. (2010) found that those treated with therapeutic formulas had catch-up growth and biochemical improvement. The authors concluded that breast milk, which is high in carbohydrates, is not a suitable diet for such patients. Dietary macronutrient formula types with higher protein levels are good sources of food. Vitamin D supplementation may help alleviate neuropsychiatric disturbances.</p><p>In a review, Okano et al. (2019) stated that treatment of infants with NICCD with lactose-free formula supplemented with MCT oil is an appropriate dietary intervention. Supplementation with lipid soluble vitamins, particularly vitamin K, may be helpful in the setting of cholestasis. Okano et al. (2019) also noted that intravenous treatment with a high glucose-containing fluid may precipitate liver failure. Dietary intake in childhood and beyond should be lower in carbohydrates and higher in fat and protein compared to a standard diet. </p>
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<span class="mim-font">
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<strong>Mapping</strong>
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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 7q21.3 by homozygosity mapping analysis of individuals from 18 consanguineous unions. </p>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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<p>In 3 neonates with neonatal-onset type II citrullinemia, Ohura et al. (2001) identified mutations in the SLC25A13 gene. The sibs were homozygous for an IVS11+1G-A mutation (603859.0002), and the third child was a compound heterozygote for the same mutation and the 851del4 mutation (603859.0001). Ohura et al. (2001) concluded that there may be a variety of liver diseases related to mutations in the SLC25A13 gene in children. </p><p>Tomomasa et al. (2001) found that the patients they studied were homozygous for the IVS11+1G-A mutation in the SLC25A13 gene. </p><p>Tazawa et al. (2001) also identified mutations in the SLC25A13 gene in 3 children with neonatal-onset type II citrullinemia. </p>
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<strong>Pathogenesis</strong>
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<p>Saheki and Kobayashi (2002) concluded that citrin deficiency causes 2 different phenotypes, NICCD in neonates and CTLN2 in adults (603471), 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>
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<p>Type II citrullinemia, both neonatal and adult onset, appears to be found almost exclusively in Japan.</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>Yamaguchi et al. (2002) referred to 2 Chinese CTLN2 patients in Taiwan and a Vietnamese NICCD patient in Australia who had the same SLC25A13 mutations as those identified in Japanese patients. Among 1,315 Japanese individuals tested, 18 were found to be carriers of an SLC25A13 mutation; this provided an estimate of minimally 1 in 21,000 for homozygotes. </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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<strong>Nomenclature</strong>
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<p>Yamaguchi et al. (2002) designated the neonatal/infantile form of type II citrullinemia as NICCD (neonatal intrahepatic cholestasis caused by citrin deficiency). </p>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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</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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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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<p class="mim-text-font">
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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.
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Naito, E., Ito, M., Matsuura, S., Yokota, I., Saijo, T., Ogawa, Y., Kitamura, S., Kobayashi, K., Saheki, T., Nishimura, Y., Sakura, N., Kuroda, Y.
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<strong>Type II citrullinaemia (citrin deficiency) in a neonate with hypergalactosaemia detected by mass screening.</strong>
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J. Inherit. Metab. Dis. 25: 71-76, 2002.
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<p class="mim-text-font">
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Ohura, T., Kobayashi, K., Tazawa, Y., Nishi, I., Abukawa, D., Sakamoto, O., Iinuma, K., Saheki, T.
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<strong>Neonatal presentation of adult-onset type II citrullinemia.</strong>
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Hum. Genet. 108: 87-90, 2001.
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Okano, Y., Ohura, T., Sakamoto, O., Inui, A.
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<strong>Current treatment for citrin deficiency during NICCD and adaptation/compensation stages: strategy to prevent CTLN2.</strong>
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Molec. Genet. Metab. 127: 175-183, 2019.
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[PubMed: 31255436]
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[Full Text: https://doi.org/10.1016/j.ymgme.2019.06.004]
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<p class="mim-text-font">
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Saheki, T., Kobayashi, K.
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<strong>Mitochondrial aspartate glutamate carrier (citrin) deficiency as the cause of adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD).</strong>
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J. Hum. Genet. 47: 333-341, 2002.
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[PubMed: 12111366]
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[Full Text: https://doi.org/10.1007/s100380200046]
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Song, Y.-Z., Deng, M., Chen, F.-P., Wen, F., Guo, L., Cao, S.-L., Gong, J., Xu, H., Jiang, G.-Y., Zhong, L., Kobayashi, K., Saheki, T., Wang, Z.-N.
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<strong>Genotypic and phenotypic features of citrin deficiency: five-year experience in a Chinese pediatric center.</strong>
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Int. J. Molec. Med. 28: 33-40, 2011.
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[PubMed: 21424115]
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[Full Text: https://doi.org/10.3892/ijmm.2011.653]
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<p class="mim-text-font">
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Song, Y.-Z., Guo, L., Yang, Y.-L., Han, L.-S., Kobayashi, K., Saheki, T. Failure to thrive and dyslipidemia caused by citrin deficiency.
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<strong>a novel clinical phenotype.</strong>
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Chin. J. Contemp. Pediat. 11: 328-332, 2009.
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Song, Y.-Z., Wen, F., Chen, F.-P., Kobayashi, K., Saheki, T.
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<strong>Neonatal intraphepatic cholestasis caused by citrin deficiency: efficacy of therapeutic formulas and update of clinical outcomes.</strong>
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Jpn. J. Inherit. Metab. Dis. 26: 57-69, 2010.
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Tamamori, A., Okano, Y., Ozaki, H., Fujimoto, A., Kajiwara, M., Fukuda, K., Kobayashi, K., Saheki, T., Tagami, Y., Yamano, T.
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<strong>Neonatal intrahepatic cholestasis caused by citrin deficiency: severe hepatic dysfunction in an infant requiring liver transplantation.</strong>
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Europ. J. Pediat. 161: 609-613, 2002.
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[PubMed: 12424587]
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[Full Text: https://doi.org/10.1007/s00431-002-1045-2]
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Tazawa, Y., Kobayashi, K., Ohura, T., Abukawa, D., Nishinomiya, F., Hosoda, Y., Yamashita, M., Nagata, I., Kono, Y., Yasuda, T., Yamaguchi, N., Saheki, T.
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<strong>Infantile cholestatic jaundice associated with adult-onset type II citrullinemia.</strong>
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J. Pediat. 138: 735-740, 2001.
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[PubMed: 11343052]
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[Full Text: https://doi.org/10.1067/mpd.2001.113264]
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Tomomasa, T., Kobayashi, K., Kaneko, H., Shimura, H., Fukusato, T., Tabata, M., Inoue, Y., Ohwada, S., Kasahara, M., Morishita, Y., Kimura, M., Saheki, T., Morikawa, A.
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<strong>Possible clinical and histologic manifestations of adult-onset type II citrullinemia in early infancy.</strong>
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J. Pediat. 138: 741-743, 2001.
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[PubMed: 11343053]
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[Full Text: https://doi.org/10.1067/mpd.2001.113361]
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Yamaguchi, N., Kobayashi, K., Yasuda, T., Nishi, I., Iijima, M., Nakagawa, M., Osame, M., Kondo, I., Saheki, T.
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<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>
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Hum. Mutat. 19: 122-130, 2002.
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[PubMed: 11793471]
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[Full Text: https://doi.org/10.1002/humu.10022]
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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: 11153906]
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[Full Text: https://doi.org/10.1007/s004390000430]
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Hilary J. Vernon - updated : 04/21/2020<br>Ada Hamosh - updated : 01/08/2015<br>Cassandra L. Kniffin - updated : 7/19/2011<br>Cassandra L. Kniffin - updated : 11/8/2005<br>Cassandra L. Kniffin - updated : 8/11/2004<br>Cassandra L. Kniffin - reorganized : 8/15/2002<br>Victor A. McKusick - updated : 2/26/2002<br>Deborah L. Stone - updated : 11/21/2001
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accessible. Unfortunately, it is not free to produce. Expert curators
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Thank you in advance for your generous support, <br />
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Ada Hamosh, MD, MPH <br />
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Scientific Director, OMIM <br />
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