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- #311250 - ORNITHINE TRANSCARBAMYLASE DEFICIENCY, HYPERAMMONEMIA DUE TO
- OMIM
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<span class="h4">#311250</span>
<br />
<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/311250"><strong>Clinical Synopsis</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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<li role="presentation" style="margin-left: 1em">
<a href="#clinicalFeatures">Clinical Features</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#diagnosis">Diagnosis</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#clinicalManagement">Clinical Management</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#populationGenetics">Population Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<a href="#seeAlso"><strong>See Also</strong></a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=ORNITHINE TRANSCARBAMYLASE DEFICIENCY, HYPERAMMONEMIA DUE TO" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=168&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>
<div><a href="#mimGeneReviewsFold" id="mimGeneReviewsToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling."><span id="mimGeneReviewsToggleTriangle" class="small" style="margin-left: -0.8em;">&#9658;</span>Gene Reviews</div>
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<div style="margin-left: 0.5em;"><a href="https://www.ncbi.nlm.nih.gov/books/NBK1217/" title="Urea Cycle Disorders Overview" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Urea Cycle Disorders Overv…</a></div><div style="margin-left: 0.5em;"><a href="https://www.ncbi.nlm.nih.gov/books/NBK154378/" title="Ornithine Transcarbamylase Deficiency" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Ornithine Transcarbamylase…</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/5412" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
<div><a href="https://medlineplus.gov/genetics/condition/ornithine-transcarbamylase-deficiency" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=311250[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>
<div><a href="https://www.acmg.net/PDFLibrary/Decreased-Citrulline.pdf" class="mim-tip-hint" title="Information and resources for newborn screening and genetics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Newborn Screening', 'domain': 'www.acmg.net'})">Newborn Screening</a></div>
<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=664" 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>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
<span class="panel-title">
<span class="small">
<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Animal Models</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.alliancegenome.org/disease/DOID:9271" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
<div><a href="http://www.informatics.jax.org/disease/311250" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
<div><a href="https://omia.org/OMIA002383/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
</div>
</div>
</div>
<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
<span class="panel-title">
<span class="small">
<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
<div style="display: table-row">
<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Cell Lines</div>
</div>
</a>
</span>
</span>
</div>
<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:311250" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
</div>
</div>
</div>
</div>
</div>
</div>
<span>
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
&nbsp;
</span>
</span>
</div>
<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>SNOMEDCT:</strong> 80908008<br />
<strong>ICD10CM:</strong> E72.4<br />
<strong>ORPHA:</strong> 664<br />
<strong>DO:</strong> 9271<br />
">ICD+</a>
</div>
<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
311250
</span>
</span>
</div>
</div>
<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
ORNITHINE TRANSCARBAMYLASE DEFICIENCY, HYPERAMMONEMIA DUE TO
</span>
</h3>
</div>
<div>
<br />
</div>
<div>
<a id="alternativeTitles" class="mim-anchor"></a>
<div>
<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
</div>
<div>
<h4>
<span class="mim-font">
ORNITHINE CARBAMOYLTRANSFERASE DEFICIENCY<br />
OTC DEFICIENCY
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/X/169?start=-3&limit=10&highlight=169">
Xp11.4
</a>
</span>
</td>
<td>
<span class="mim-font">
Ornithine transcarbamylase deficiency
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/311250"> 311250 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="X-linked">XL</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">
OTC
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300461"> 300461 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
<div>
<div class="btn-group ">
<a href="/clinicalSynopsis/311250" 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>
&nbsp;
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
</button>
<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/311250" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/311250" 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">
- X-linked <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/263934009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">263934009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0241764&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0241764</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001417" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001417</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001417" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001417</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 />
</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> Gastrointestinal </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Protein avoidance <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839531&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839531</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002038" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002038</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002038" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002038</a>]</span><br /> -
Vomiting <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422400008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422400008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/300359004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">300359004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249497008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249497008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R11.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R11.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R11.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R11.10</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042963&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042963</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002013" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002013</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002013" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002013</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> NEUROLOGIC </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Central Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Lethargy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/214264003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">214264003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R53.83" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R53.83</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0023380&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023380</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001254" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001254</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001254" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001254</a>]</span><br /> -
Episodic ataxia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/421455009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">421455009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1720189&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1720189</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002131" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002131</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002131" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002131</a>]</span><br /> -
Coma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/371632003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">371632003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405809000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405809000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R40.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R40.20</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R40.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R40.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/780.01" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">780.01</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0543874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0543874</a>, <a href="https://bioportal.bioontology.org/search?q=C3146279&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3146279</a>, <a href="https://bioportal.bioontology.org/search?q=C0009421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009421</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001259" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001259</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001259" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001259</a>]</span><br /> -
Seizures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91175000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91175000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span><br /> -
Cerebral edema <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/2032001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">2032001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G93.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G93.6</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/348.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">348.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0006114&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0006114</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002181" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002181</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002181" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002181</a>]</span><br /> -
Developmental delay <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248290002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248290002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/224958001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">224958001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F88</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/315.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">315.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0557874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0557874</a>, <a href="https://bioportal.bioontology.org/search?q=C0424605&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424605</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span><br /> -
Mental retardation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/228156007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">228156007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/110359009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">110359009</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/317-319.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">317-319.99</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714756&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714756</a>, <a href="https://bioportal.bioontology.org/search?q=C0025362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span><br /> -
Stroke (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/230690007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">230690007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I63.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I63.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038454&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038454</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001297" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001297</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001297" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001297</a>]</span><br />
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<span class="h5 mim-font">
<em> Behavioral Psychiatric Manifestations </em>
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<div style="margin-left: 2em;">
<span class="mim-font">
- Irritability <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/55929007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">55929007</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/799.22" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">799.22</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0022107&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022107</a>, <a href="https://bioportal.bioontology.org/search?q=C2700617&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2700617</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000737" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000737</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000737" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000737</a>]</span><br />
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<div>
<span class="h5 mim-font">
<strong> METABOLIC FEATURES </strong>
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<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Episodic ammonia intoxication <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839541&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839541</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001951" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001951</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001951" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001951</a>]</span><br /> -
Respiratory alkalosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/111378004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">111378004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E87.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E87.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0002064&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0002064</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001950" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001950</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001950" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001950</a>]</span><br />
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<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
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<div style="margin-left: 2em;">
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- Hyperammonemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/9360008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">9360008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E72.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E72.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C5574662&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5574662</a>, <a href="https://bioportal.bioontology.org/search?q=C0220994&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0220994</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001987" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001987</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001987" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001987</a>]</span><br /> -
Low plasma citrulline <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839532&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839532</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003572" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003572</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003572" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003572</a>]</span><br /> -
Low plasma arginine <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855982&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855982</a>]</span><br /> -
High plasma glutamine <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839533&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839533</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003217" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003217</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003217" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003217</a>]</span><br /> -
High plasma asparagine <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551055&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551055</a>]</span><br /> -
High urinary orotic acid <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839534&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839534</a>]</span><br /> -
High ornithine <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551056&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551056</a>]</span><br /> -
Hepatic ornithine transcarbamylase deficiency <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839535&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839535</a>]</span><br />
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<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
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<span class="mim-font">
- Two types - lethal neonatal and less severe, late onset<br /> -
Clinical spectrum in males ranges from lethal neonatal onset to milder forms with first recognized episode in late childhood or even in adulthood<br /> -
Carrier females may present with postpartum hyperammonemia<br /> -
Some carrier females have episodes of significant hyperammonemia in infancy or childhood<br /> -
Prevalence of 1 in 40,000 to 1 in 80,000<br />
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<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
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<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Caused by mutation in the ornithine transcarbamylase gene (OTC, <a href="/entry/300461#0001">300461.0001</a>)<br />
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<p>A number sign (#) is used with this entry because ornithine transcarbamylase deficiency is caused by mutation in the gene encoding ornithine carbamoyltransferase (OTC; <a href="/entry/300461">300461</a>) on chromosome Xp11.</p>
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<p>Ornithine transcarbamylase deficiency is an X-linked inborn error of metabolism of the urea cycle, which causes hyperammonemia. The disorder is treatable with supplemental dietary arginine and low protein diet.</p><p>Urea cycle disorders are characterized by the triad of hyperammonemia, encephalopathy, and respiratory alkalosis. Five disorders involving different defects in the biosynthesis of the enzymes of the urea cycle have been described: OTC deficiency, carbamyl phosphate synthetase deficiency (<a href="/entry/237300">237300</a>), argininosuccinate synthetase deficiency, or citrullinemia (<a href="/entry/215700">215700</a>), argininosuccinate lyase deficiency (<a href="/entry/207900">207900</a>), and arginase deficiency (<a href="/entry/207800">207800</a>).</p>
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<strong>Clinical Features</strong>
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<p><a href="#73" class="mim-tip-reference" title="Russell, A., Levin, B., Oberholzer, V. G., Sinclair, L. &lt;strong&gt;Hyperammonaemia. A new instance of an inborn enzymatic defect of the biosynthesis of urea.&lt;/strong&gt; Lancet 280: 699-700, 1962. Note: Originally Volume II.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/13975632/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;13975632&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(62)90508-1&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="13975632">Russell et al. (1962)</a> described 2 cousins with chronic ammonia intoxication and mental deterioration. By liver biopsy, the activity of hepatic OTC was shown to be very low. A defect was presumed to be present in urea synthesis at the level of conversion of ornithine to citrulline. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13975632" 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="#47" class="mim-tip-reference" title="Levin, B., Abraham, J. M., Oberholzer, V. G., Burgess, E. A. &lt;strong&gt;Hyperammonaemia: a deficiency of liver ornithine transcarbamylase. Occurrence in mother and child.&lt;/strong&gt; Arch. Dis. Child. 44: 152-161, 1969.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5779426/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5779426&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/adc.44.234.152&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="5779426">Levin et al. (1969)</a> reported an affected female infant whose mother had an aversion to protein and raised plasma ammonia levels, whereas the father was normal. In another infant, a male, <a href="#47" class="mim-tip-reference" title="Levin, B., Abraham, J. M., Oberholzer, V. G., Burgess, E. A. &lt;strong&gt;Hyperammonaemia: a deficiency of liver ornithine transcarbamylase. Occurrence in mother and child.&lt;/strong&gt; Arch. Dis. Child. 44: 152-161, 1969.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5779426/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5779426&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/adc.44.234.152&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="5779426">Levin et al. (1969)</a> found what they considered a variant of the usual hyperammonemia caused by OTC deficiency, presumably due to a different enzymatic change. Enzyme activity was 25% of normal, rather than 5 to 7% of normal as in other cases, and other properties of the enzyme showed differences from the normal. The clinical picture was milder than in the usual cases. <a href="#33" class="mim-tip-reference" title="Holmes, A. K., Fowler, B., Sardharwalla, I. B. &lt;strong&gt;Late-onset ornithine carbamyl transferase deficiency in a male patient: detailed enzyme studies.&lt;/strong&gt; J. Inherit. Metab. Dis. 10 (suppl. 2): 299-301, 1987."None>Holmes et al. (1987)</a> also described a mild variant of OTC deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5779426" 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>Campbell et al. (<a href="#12" class="mim-tip-reference" title="Campbell, A. G. M., Rosenberg, L. E., Snodgrass, P. J., Nuzum, C. T. &lt;strong&gt;Lethal neonatal hyperammonaemia due to complete ornithine-transcarbamylase deficiency. (Letter)&lt;/strong&gt; Lancet 298: 217-218, 1971. Note: Originally Volume II.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4104881/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4104881&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(71)90931-7&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4104881">1971</a>, <a href="#13" class="mim-tip-reference" title="Campbell, A. G. M., Rosenberg, L. E., Snodgrass, P. J., Nuzum, C. T. &lt;strong&gt;Ornithine transcarbamylase deficiency: a cause of lethal neonatal hyperammonemia in males.&lt;/strong&gt; New Eng. J. Med. 288: 1-6, 1973.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4681895/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4681895&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM197301042880101&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4681895">1973</a>) reported lethal neonatal hyperammonemia due to complete ornithine transcarbamylase deficiency. They suggested that mutation in the gene encoding the enzyme may lead to partial deficiency in heterozygous females and to complete deficiency in hemizygous males. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4104881+4681895" 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="#83" class="mim-tip-reference" title="Thaler, M. M., Hoogenraad, N. J., Boswell, M. &lt;strong&gt;Reye&#x27;s syndrome due to a novel protein-tolerant variant of ornithine-transcarbamylase deficiency.&lt;/strong&gt; Lancet 304: 438-440, 1974. Note: Originally Volume II.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4137171/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4137171&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(74)91819-4&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4137171">Thaler et al. (1974)</a> described a 'novel protein tolerant variant' of OTC deficiency in a child with encephalopathy with fatty visceral degeneration suggestive of Reye syndrome. <a href="#45" class="mim-tip-reference" title="Krieger, I., Snodgrass, P. J., Roskamp, J. &lt;strong&gt;Atypical clinical course of ornithine transcarbamylase deficiency due to a new mutant (comparison with Reye&#x27;s disease).&lt;/strong&gt; J. Clin. Endocr. Metab. 48: 388-392, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/429491/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;429491&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1210/jcem-48-3-388&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="429491">Krieger et al. (1979)</a> reported a male infant with OTC deficiency who was relatively symptom free for 4 months, but gradually developed severe spasticity due to cerebral atrophy, and died at 13 months of age. Liver OTC activity was 1.5% of normal. The authors noted that the clinical picture of OTC deficiency during acute exacerbations with microvesicular fat accumulation in the liver may suggest Reye syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=429491+4137171" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Bruton, C. J., Corsellis, J. A. N., Russell, A. &lt;strong&gt;Hereditary hyperammonemia.&lt;/strong&gt; Brain 93: 423-434, 1970.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5310321/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5310321&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/brain/93.2.423&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="5310321">Bruton et al. (1970)</a> described astrocyte transformation to Alzheimer type II glia, a feature of any form of hyperammonemia. <a href="#43" class="mim-tip-reference" title="Kornfeld, M., Woodfin, B. M., Papile, L., Davis, L. E., Bernard, L. R. &lt;strong&gt;Neuropathology of ornithine carbamyl transferase deficiency.&lt;/strong&gt; Acta Neuropath. 65: 261-264, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3976361/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3976361&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00687006&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3976361">Kornfeld et al. (1985)</a> reported neuropathologic findings in 2 cases of OTC deficiency. A 3-day-old boy showed gliosis mainly in the brainstem, and a 2-year-old girl showed widespread gliosis and ulegyria of the cerebral cortex, as well as atrophy in the internal granular layer of the cerebellum. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3976361+5310321" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Drogari, E., Leonard, J. V. &lt;strong&gt;Late onset ornithine carbamoyl transferase deficiency in males.&lt;/strong&gt; Arch. Dis. Child. 63: 1363-1367, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3202644/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3202644&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/adc.63.11.1363&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3202644">Drogari and Leonard (1988)</a> described 6 affected boys with relatively late onset of clinical symptoms. One of them was a boy who during childhood was considered a 'very difficult child, introverted with volcanic tempers.' At the age of 12 years, he had an episode of confusion for which he was admitted to hospital, but no cause was found. At the age of 14 years, he was admitted to hospital deeply unconscious after a high protein meal the night before admission. Urine orotic acid excretion was raised, and his mother was found to be a carrier. Thereafter, he was treated with a low protein diet, arginine supplements, and sodium benzoate. He had further episodes of hyperammonemia, however, particularly precipitated by energy restriction. At the age of 18 years he performed commendably in examinations and was accepted for medical school. Finkelstein et al. (<a href="#18" class="mim-tip-reference" title="Finkelstein, J. E., Hauser, E., Brusilow, S. W. &lt;strong&gt;Late onset ornithine transcarbamylase deficiency (OTCD) in males. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 45 (suppl.): A5, 1989."None>1989</a>, <a href="#19" class="mim-tip-reference" title="Finkelstein, J. E., Hauser, E. R., Leonard, C. O., Brusilow, S. W. &lt;strong&gt;Late-onset ornithine transcarbamylase deficiency in male patients.&lt;/strong&gt; J. Pediat. 117: 897-902, 1990. Note: Erratum: J. Pediat. 118: 326 only, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2246687/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2246687&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(05)80129-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2246687">1990</a>) described 21 male patients who presented after age 28 days with what the authors defined as late-onset OTC deficiency. The patients appeared normal at birth, but irritability, vomiting and lethargy, which were often episodic, developed later. The age of presentation ranged from 2 months to 44 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2246687+3202644" 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>Partial deficiency in the male, a presumably allelic form, was reported by <a href="#55" class="mim-tip-reference" title="Matsuda, I., Arashima, S., Nambu, H., Takekoshi, Y., Anakura, M. &lt;strong&gt;Hyperammonemia due to a mutant enzyme of ornithine transcarbamylase.&lt;/strong&gt; Pediatrics 48: 595-600, 1971.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5114747/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5114747&lt;/a&gt;]" pmid="5114747">Matsuda et al. (1971)</a> and by <a href="#63" class="mim-tip-reference" title="Oizumi, J., Ng, W. G., Koch, R., Shaw, K. N. F., Sweetman, L., Velazquez, A., Donnell, G. N. &lt;strong&gt;Partial ornithine transcarbamylase deficiency associated with recurrent hyperammonemia, lethargy and depressed sensorium.&lt;/strong&gt; Clin. Genet. 25: 538-542, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6733950/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6733950&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1984.tb00498.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6733950">Oizumi et al. (1984)</a>. <a href="#63" class="mim-tip-reference" title="Oizumi, J., Ng, W. G., Koch, R., Shaw, K. N. F., Sweetman, L., Velazquez, A., Donnell, G. N. &lt;strong&gt;Partial ornithine transcarbamylase deficiency associated with recurrent hyperammonemia, lethargy and depressed sensorium.&lt;/strong&gt; Clin. Genet. 25: 538-542, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6733950/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6733950&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1984.tb00498.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6733950">Oizumi et al. (1984)</a> reported the case of a 6-year-old boy who had intermittent coma with hyperammonemia precipitated by infections. Liver biopsy showed OTC activity 16% of normal. The mother showed elevated orotic acid excretion in the urine following protein load. Supplementation of dietary arginine abolished the episodes of hyperammonemia in the boy. <a href="#56" class="mim-tip-reference" title="Matsuda, I., Nagata, N., Matsuura, T., Oyanagi, K., Tada, K., Narisawa, K., Kitagawa, T., Sakiyama, T., Yamashita, F., Yoshino, M. &lt;strong&gt;Retrospective survey of urea cycle disorders: Part 1. Clinical and laboratory observations of thirty-two Japanese male patients with ornithine transcarbamylase deficiency.&lt;/strong&gt; Am. J. Med. Genet. 38: 85-89, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2012137/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2012137&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320380119&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2012137">Matsuda et al. (1991)</a> described the clinical and laboratory features of 32 Japanese patients with OTC deficiency. They divided their patients into 3 groups, based on clinical manifestations and age of onset: group 1 (0 to 28 days), group 2 (29 days to 5 years), and group 3 (greater than 5 years). The lowest mortality and incidence of mental retardation was among the group 2 patients. Patients in groups 1 and 3 had similar mortality rates and enzyme activities. These patients had the highest citrulline levels and were asymptomatic prior to their first episode of hyperammonemia. The authors emphasized that the incidence of late-onset OTC deficiency is higher than previously recognized. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2012137+6733950+5114747" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Anadiotis, G., Ierardi-Curto, L., Kaplan, P. B., Berry, G. T. &lt;strong&gt;Ornithine transcarbamylase deficiency and pancreatitis.&lt;/strong&gt; J. Pediat. 138: 123-124, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11148526/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11148526&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1067/mpd.2001.109792&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11148526">Anadiotis et al. (2001)</a> reported a 15-year-old male patient with OTC deficiency who developed pancreatitis while taking a low protein diet, citrulline, and sodium phenylbutyrate. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11148526" 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="#46" class="mim-tip-reference" title="Lee, J.-Y., Chang, S.-E., Suh, C.-W., Choi, J.-H., Sung, K.-J., Moon, K.-C., Koh, J.-K. &lt;strong&gt;A case of acrodermatitis enteropathica-like dermatosis caused by ornithine transcarbamylase deficiency.&lt;/strong&gt; J. Am. Acad. Derm. 46: 965-967, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12063505/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12063505&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1067/mjd.2002.120595&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12063505">Lee et al. (2002)</a> noted that there have been several reports of acrodermatitis enteropathica-like dermatosis in association with inborn errors of the urea cycle, in citrullinemia associated with argininosuccinate synthase deficiency (<a href="#24" class="mim-tip-reference" title="Goldblum, O. M., Brusilow, S. W., Maldonado, Y. A., Farmer, E. R. &lt;strong&gt;Neonatal citrullinemia associated with cutaneous manifestations and arginine deficiency.&lt;/strong&gt; J. Am. Acad. Derm. 14: 321-326, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3950131/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3950131&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0190-9622(86)70035-2&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3950131">Goldblum et al., 1986</a>), and in carbamoyl phosphate synthetase deficiency (<a href="#41" class="mim-tip-reference" title="Kline, J. J., Hug, G., Schubert, W. K., Berry, H. &lt;strong&gt;Arginine deficiency syndrome: its occurrence in carbamyl phosphate synthetase deficiency.&lt;/strong&gt; Am. J. Dis. Child. 135: 437-442, 1981.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7234771/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7234771&lt;/a&gt;]" pmid="7234771">Kline et al., 1981</a>). <a href="#46" class="mim-tip-reference" title="Lee, J.-Y., Chang, S.-E., Suh, C.-W., Choi, J.-H., Sung, K.-J., Moon, K.-C., Koh, J.-K. &lt;strong&gt;A case of acrodermatitis enteropathica-like dermatosis caused by ornithine transcarbamylase deficiency.&lt;/strong&gt; J. Am. Acad. Derm. 46: 965-967, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12063505/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12063505&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1067/mjd.2002.120595&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12063505">Lee et al. (2002)</a> speculated that since arginine represents such a large proportion of the amino acid composition of epidermal keratins, arginine deficiency associated with urea cycle defects may contribute to compromised epidermal barrier function and skin lesions in affected infants. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=12063505+7234771+3950131" 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="#48" class="mim-tip-reference" title="Lien, J., Nyhan, W. L., Barshop, B. A. &lt;strong&gt;Fatal initial adult-onset presentation of urea cycle defect.&lt;/strong&gt; Arch. Neurol. 64: 1777-1779, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18071043/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;18071043&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.64.12.1777&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="18071043">Lien et al. (2007)</a> reported a 52-year-old man who died suddenly of hyperammonemia after routine surgery for removal of a throat polyp. Eight days after surgery, he developed confusion, ataxia, and paranoia, which progressed to seizures, cerebral edema, coma, and death within 3 days. Prior medical history was unremarkable. The patient's asymptomatic 20-year-old daughter presented for prenatal evaluation, and her twin boys were both found to be carriers of a mutation in the OTC gene. The mother was heterozygous for the mutation, but DNA analysis on autopsy samples from her father were unsuccessful. Both baby boys were healthy on a low protein diet. <a href="#48" class="mim-tip-reference" title="Lien, J., Nyhan, W. L., Barshop, B. A. &lt;strong&gt;Fatal initial adult-onset presentation of urea cycle defect.&lt;/strong&gt; Arch. Neurol. 64: 1777-1779, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/18071043/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;18071043&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneur.64.12.1777&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="18071043">Lien et al. (2007)</a> emphasized the late onset and unusual presentation of OTC deficiency in the older man. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18071043" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a review of inherited metabolic disorders and stroke, <a href="#82" class="mim-tip-reference" title="Testai, F. D., Gorelick, P. B. &lt;strong&gt;Inherited metabolic disorders and stroke part 2: homocystinuria, organic acidurias, and urea cycle disorders.&lt;/strong&gt; Arch. Neurol. 67: 148-153, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20142522/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20142522&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneurol.2009.333&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20142522">Testai and Gorelick (2010)</a> noted that patients with urea cycle defects, including CPS1 deficiency (<a href="/entry/237300">237300</a>), OTC deficiency, and citrullinemia (<a href="/entry/215700">215700</a>) rarely have strokes. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20142522" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#7" class="mim-tip-reference" title="Batshaw, M. L., Tuchman, M., Summar, M., Seminara, J., Members of the Urea Cycle Disorders Consortium. &lt;strong&gt;A longitudinal study of urea cycle disorders.&lt;/strong&gt; Molec. Genet. Metab. 113: 127-130, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25135652/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;25135652&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2014.08.001&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="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. The most common disorder was ornithine transcarbamylase deficiency, accounting for more than half of the participants. The overall prevalence of UCDs in the population was calculated as 1 per 35,000, with two-thirds presenting initial symptoms after the neonatal period. <a href="#7" class="mim-tip-reference" title="Batshaw, M. L., Tuchman, M., Summar, M., Seminara, J., Members of the Urea Cycle Disorders Consortium. &lt;strong&gt;A longitudinal study of urea cycle disorders.&lt;/strong&gt; Molec. Genet. Metab. 113: 127-130, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25135652/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;25135652&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2014.08.001&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="25135652">Batshaw et al. (2014)</a> found the mortality rate to be 24% in neonatal-onset cases and 11% in late-onset cases. The most common precipitant of clinical hyperammonemic episodes in the post-neonatal period was intercurrent infections. Elevations in both blood ammonia and glutamine appeared to be biomarkers for neurocognitive outcome. In terms of chronic treatment, low protein diet appeared to result in normal weight but decreased linear growth, while nitrogen scavenger therapy with phenylbutyrate resulted in low levels of branched chain amino acids. <a href="#7" class="mim-tip-reference" title="Batshaw, M. L., Tuchman, M., Summar, M., Seminara, J., Members of the Urea Cycle Disorders Consortium. &lt;strong&gt;A longitudinal study of urea cycle disorders.&lt;/strong&gt; Molec. Genet. Metab. 113: 127-130, 2014.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/25135652/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;25135652&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2014.08.001&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="25135652">Batshaw et al. (2014)</a> found an unexpectedly high risk for hepatic dysfunction in patients with ornithine transcarbamylase deficiency. <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>Heterozygous Females</em></strong></p><p>
<a href="#71" class="mim-tip-reference" title="Rowe, P. C., Newman, S. L., Brusilow, S. W. &lt;strong&gt;Natural history of symptomatic partial ornithine transcarbamylase deficiency.&lt;/strong&gt; New Eng. J. Med. 314: 541-547, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3945292/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3945292&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM198602273140903&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3945292">Rowe et al. (1986)</a> reviewed 13 symptomatic female heterozygotes. They presented as early as the first week of life or as late as the sixth year. Symptoms before diagnosis were nonspecific: episodic extreme irritability (100%), episodic vomiting and lethargy (100%), protein avoidance (92%), ataxia (77%), stage II coma (46%), delayed growth (38%), developmental delay (38%), and seizures (23%). Onset at the time of weaning from breast milk was frequent. Including the proband, 42% of females in the 13 families had symptoms. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3945292" 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="#23" class="mim-tip-reference" title="Gilchrist, J. M., Coleman, R. A. &lt;strong&gt;Ornithine transcarbamylase deficiency: adult onset of severe symptoms.&lt;/strong&gt; Ann. Intern. Med. 106: 556-558, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3826955/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3826955&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.7326/0003-4819-106-4-556&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3826955">Gilchrist and Coleman (1987)</a> reported 2 heterozygous females who had late onset of severe symptoms. Encephalopathy and focal neurologic deficits began at age 36 years in 1 and at age 38 years in the other. The second had increased urine orotate after a protein meal and had had a lifelong aversion to eating meat, which usually precipitated headaches. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3826955" 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="Arn, P., Hauser, B., Maestri, N., Herman, G., Thomas, G. H., Brusilow, S. W. &lt;strong&gt;Hyperammonemic coma in adult females heterozygous at the ornithine transcarbamylase locus (OTCDH). (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 45 (suppl.): A3, 1989."None>Arn et al. (1989)</a> discussed phenotypic effects of heterozygosity for mutations in the OTC gene. <a href="#3" class="mim-tip-reference" title="Arn, P. H., Hauser, E. R., Thomas, G. H., Herman, G., Hess, D., Brusilow, S. W. &lt;strong&gt;Hyperammonemia in women with a mutation at the ornithine carbamoyltransferase locus: a cause of postpartum coma.&lt;/strong&gt; New Eng. J. Med. 322: 1652-1655, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2342525/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2342525&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM199006073222307&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2342525">Arn et al. (1990)</a> reported that otherwise normal women who are carriers of a mutant OTC allele are at increased risk for hyperammonemic coma, especially during puerperium. They recommended that any woman who presents with an episode of progressive lethargy and stupor, evidence of acute cortical dysfunction, or coma, especially during pregnancy, be examined for OTC deficiency by pedigree analysis, a search for a history of previous episodes, and the measurement of plasma ammonium and, if immediately available, plasma glutamine levels. The early identification of hyperammonemia provides an opportunity to correct plasma ammonium levels by intravenous therapy with sodium benzoate, sodium phenylacetate, and arginine hydrochloride. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2342525" 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="#46" class="mim-tip-reference" title="Lee, J.-Y., Chang, S.-E., Suh, C.-W., Choi, J.-H., Sung, K.-J., Moon, K.-C., Koh, J.-K. &lt;strong&gt;A case of acrodermatitis enteropathica-like dermatosis caused by ornithine transcarbamylase deficiency.&lt;/strong&gt; J. Am. Acad. Derm. 46: 965-967, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12063505/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12063505&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1067/mjd.2002.120595&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12063505">Lee et al. (2002)</a> reported a female infant with skin lesions resembling acrodermatitis enteropathica who was subsequently found to have OTC deficiency. Infectious causes and zinc deficiency were ruled out, and resolution of the eruption occurred after arginine and citrulline supplementation was instituted. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12063505" 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="#84" class="mim-tip-reference" title="Torkzaban, M., Haddad, A., Baxter, J. K., Berghella, V., Gahl, W. A., Al-Kouatly, H. &lt;strong&gt;Maternal ornithine transcarbamylase deficiency, a genetic condition associated with high maternal and neonatal mortality every clinician should know: a systematic review.&lt;/strong&gt; Am. J. Med. Genet. 179A: 2091-2100, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/31441224/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;31441224&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.61329&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="31441224">Torkzaban et al. (2019)</a> reported pregnancy outcomes in 36 women who were heterozygous for OTC deficiency based on a review of the literature. Twenty women were known to be heterozygous prior to pregnancy; of these 20 women, 7 had neurologic or psychiatric symptoms during pregnancy or postpartum, 3 had hyperammonemia during pregnancy, and 2 had hyperammonemia and required ICU admission and dialysis postpartum. There were no maternal deaths in this group. Of the 16 women not known to be heterozygous prior to pregnancy, 13 had neurologic or psychiatric symptoms during pregnancy or postpartum, 4 had hyperemesis gravidarum, 11 had hyperammonemia and ICU admission, and 7 required dialysis. In this group, 3 had prolonged hospitalization and there were 5 maternal deaths. <a href="#84" class="mim-tip-reference" title="Torkzaban, M., Haddad, A., Baxter, J. K., Berghella, V., Gahl, W. A., Al-Kouatly, H. &lt;strong&gt;Maternal ornithine transcarbamylase deficiency, a genetic condition associated with high maternal and neonatal mortality every clinician should know: a systematic review.&lt;/strong&gt; Am. J. Med. Genet. 179A: 2091-2100, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/31441224/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;31441224&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.61329&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="31441224">Torkzaban et al. (2019)</a> concluded that maternal heterozygous status of OTC deficiency is associated with higher maternal morbidity and mortality when it is diagnosed during pregnancy compared to when it is diagnosed prior to pregnancy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31441224" 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>Valproate Sensitivity</em></strong></p><p>
In males with OTC deficiency, sodium valproate may precipitate acute liver failure (<a href="#85" class="mim-tip-reference" title="Tripp, J. H., Hargreaves, T., Anthony, P. P., Searle, J. F., Miller, P., Leonard, J. V., Patrick, A. D., Oberholzer, V. G. &lt;strong&gt;Sodium valproate and ornithine carbamyl transferase deficiency. (Letter)&lt;/strong&gt; Lancet 317: 1165-1166, 1981. Note: Originally Volume I.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6112522/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6112522&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(81)92338-2&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6112522">Tripp et al., 1981</a>). <a href="#31" class="mim-tip-reference" title="Hjelm, M., de Silva, L. V. K., Seakins, J. W. T., Oberholzer, V. G., Rolles, C. J. &lt;strong&gt;Evidence of inherited urea cycle defect in a case of fatal valproate toxicity.&lt;/strong&gt; Brit. Med. J. 292: 23-24, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3080051/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3080051&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/bmj.292.6512.23&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3080051">Hjelm et al. (1986)</a> concluded that the vulnerability of toxic effects of valproate extends to heterozygotes as well. They described a family in which 2 daughters and a son died in childhood, all with clinical features suggesting a metabolic disorder; in one, valproate seemed to have accelerated death. They concluded that the mother was a heterozygote for OTC deficiency. Valproate sensitivity in OTC deficiency is comparable to vincristine neuropathy in Charcot-Marie-Tooth disease (<a href="/entry/118200">118200</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3080051+6112522" 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="#35" class="mim-tip-reference" title="Honeycutt, D., Callahan, K., Rutledge, L., Evans, B. &lt;strong&gt;Heterozygote ornithine transcarbamylase deficiency presenting as symptomatic hyperammonemia during initiation of valproate therapy.&lt;/strong&gt; Neurology 42: 666-668, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1549234/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1549234&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1212/wnl.42.3.666&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1549234">Honeycutt et al. (1992)</a> reported a previously undiagnosed heterozygous woman who had symptomatic hyperammonemia during initiation of valproate therapy. <a href="#40" class="mim-tip-reference" title="Kay, J. D. S., Hilton-Jones, D., Hyman, N. &lt;strong&gt;Valproate toxicity and ornithine carbamoyltransferase deficiency. (Letter)&lt;/strong&gt; Lancet 328: 1283-1284, 1986. Note: Originally Volume II.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2878165/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2878165&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(86)92714-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2878165">Kay et al. (1986)</a> had reported a similar patient. Valproate inhibits ureagenesis and can be toxic to mitochondria. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1549234+2878165" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="inheritance" class="mim-anchor"></a>
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<p><a href="#75" class="mim-tip-reference" title="Scott, C. R., Chiang-Teng, C., Goodman, S. I., Greensher, A., Mace, J. W. &lt;strong&gt;X-linked transmission of ornithine-transcarbamylase deficiency. (Letter)&lt;/strong&gt; Lancet 300: 1148 only, 1972. Note: Originally Volume II.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4117228/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4117228&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0140-6736(72)92756-0&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4117228">Scott et al. (1972)</a> presented 2 kindreds that supported X-linked recessive inheritance of OTC deficiency. <a href="#78" class="mim-tip-reference" title="Short, E. M., Conn, H. O., Snodgrass, P. J., Campbell, A. G. M., Rosenberg, L. E. &lt;strong&gt;Evidence for X-linked dominant inheritance of ornithine transcarbamylase deficiency.&lt;/strong&gt; New Eng. J. Med. 288: 7-12, 1973.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4681915/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4681915&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM197301042880102&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4681915">Short et al. (1973)</a> studied 4 families, all consistent with X-linked inheritance. In the liver of a woman heterozygous for OTC deficiency, <a href="#68" class="mim-tip-reference" title="Ricciuti, F. C., Gelehrter, T. D., Rosenberg, L. E. &lt;strong&gt;X-chromosome inactivation in human liver: confirmation of X-linkage of ornithine transcarbamylase.&lt;/strong&gt; Am. J. Hum. Genet. 28: 332-338, 1976.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/941900/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;941900&lt;/a&gt;]" pmid="941900">Ricciuti et al. (1976)</a> demonstrated 2 classes of cells, one deficient and one normal in enzyme activity. The findings of cellular mosaicism confirmed that the gene for OTC is X-linked. Thus, the evidence of X-linked dominant inheritance is based on (1) the severe nature of the disorder in males with almost complete absence of enzyme in most cases; (2) wide variation in clinical severity and in enzyme level in heterozygous women; (3) demonstration of the Lyon phenomenon in the liver of heterozygous females; and (4) demonstration of X-linkage in the mouse (see <a href="#16" class="mim-tip-reference" title="DeMars, R., LeVan, S. L., Trend, B. L., Russell, L. B. &lt;strong&gt;Abnormal ornithine carbamyltransferase in mice having the sparse-fur mutation.&lt;/strong&gt; Proc. Nat. Acad. Sci. 73: 1693-1697, 1976.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5727/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5727&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.73.5.1693&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="5727">DeMars et al., 1976</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5727+4681915+941900+4117228" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#11" class="mim-tip-reference" title="Burdakin, J. H., Norum, R. A. &lt;strong&gt;Recombination between loci for ornithine transcarbamylase (OTC) deficiency and G6PD. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 33: 38A, 1981."None>Burdakin and Norum (1981)</a> observed at least 1 recombinant in 3 opportunities for the linkage of OTC deficiency and G6PD (<a href="/entry/305900">305900</a>) on the X chromosome. The loci were later found to be at opposite ends of the X chromosome.</p>
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<p><a href="#71" class="mim-tip-reference" title="Rowe, P. C., Newman, S. L., Brusilow, S. W. &lt;strong&gt;Natural history of symptomatic partial ornithine transcarbamylase deficiency.&lt;/strong&gt; New Eng. J. Med. 314: 541-547, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3945292/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3945292&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM198602273140903&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3945292">Rowe et al. (1986)</a> suggested that family history, dietary history, episodic nonspecific symptoms, response to withdrawal of protein, and other characteristics should permit early diagnosis. In 5 patients tested, IQ was below 70 at the time of diagnosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3945292" 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>OTC is expressed in the liver and in the mucosa of the small intestine. <a href="#27" class="mim-tip-reference" title="Hamano, Y., Kodama, H., Fujikawa, Y., Tanaka, Y., Nishimura, K., Yanagisawa, M. &lt;strong&gt;Use of immunocytochemical analysis of a duodenal biopsy specimen to identify a carrier of ornithine transcarbamylase deficiency.&lt;/strong&gt; New Eng. J. Med. 318: 1521-1523, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3367962/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3367962&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM198806093182307&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3367962">Hamano et al. (1988)</a> described the identification of a carrier of OTC deficiency by means of immunocytochemical examination of a biopsy specimen from the duodenal mucosa. OTC-negative cells were distributed around 1 side of some villi, whereas OTC-positive cells were located on the other side. The epithelial cells of the intestine arise from the division of the crypt cells and then move up along the sides of the villi. The epithelium of individual crypts is thought to be composed of cells of a single parental type. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3367962" 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>About 15% of heterozygous females have life-threatening hyperammonemic comas. Both symptomatic and asymptomatic carriers show increased orotic acid excretion, especially under protein loading tests. <a href="#65" class="mim-tip-reference" title="Pelet, A., Rotig, A., Bonaiti-Pellie, C., Rabier, D., Cormier, V., Toumas, E., Hentzen, D., Saudubray, J.-M., Munnich, A. &lt;strong&gt;Carrier detection in a partially dominant X-linked disease: ornithine transcarbamylase deficiency.&lt;/strong&gt; Hum. Genet. 84: 167-171, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2298453/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2298453&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00208934&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2298453">Pelet et al. (1990)</a> found that the test is rarely negative in obligate carriers, perhaps no more often than in 8% of carriers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2298453" 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="#29" class="mim-tip-reference" title="Hauser, E. R., Finkelstein, J. E., Valle, D., Brusilow, S. W. &lt;strong&gt;Allopurinol-induced orotidinuria: a test for mutations at the ornithine carbamoyltransferase locus in women.&lt;/strong&gt; New Eng. J. Med. 322: 1641-1645, 1990. Note: Erratum: New Eng. J. Med. 336: 1335 only, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2342523/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2342523&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM199006073222305&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2342523">Hauser et al. (1990)</a> described a test that can be substituted for nitrogen loading for identification of heterozygous females. In the nitrogen loading test, there is intramitochondrial accumulation of carbamoyl phosphate. The excess carbamoyl phosphate is diffused into the cytosol where it functions as a substrate to enhance the biosynthesis of pyrimidine, resulting in the accumulation and excretion of orotic acid. In the test proposed by <a href="#29" class="mim-tip-reference" title="Hauser, E. R., Finkelstein, J. E., Valle, D., Brusilow, S. W. &lt;strong&gt;Allopurinol-induced orotidinuria: a test for mutations at the ornithine carbamoyltransferase locus in women.&lt;/strong&gt; New Eng. J. Med. 322: 1641-1645, 1990. Note: Erratum: New Eng. J. Med. 336: 1335 only, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2342523/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2342523&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM199006073222305&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2342523">Hauser et al. (1990)</a>, a single oral dose of allopurinol substitutes for the nitrogen load. The effectiveness of the method depends on the inhibitory effect of oxypurinol ribonucleotide (a metabolite of allopurinol) on orotidine monophosphate decarboxylase, which leads to the accumulation of orotidine monophosphate and its precursor orotic acid, and ultimately to orotic aciduria and orotidinuria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2342523" 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="#25" class="mim-tip-reference" title="Grompe, M., Caskey, C. T., Fenwick, R. G. &lt;strong&gt;Improved molecular diagnostics for ornithine transcarbamylase deficiency.&lt;/strong&gt; Am. J. Hum. Genet. 48: 212-222, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1671317/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1671317&lt;/a&gt;]" pmid="1671317">Grompe et al. (1991)</a> offered a diagnostic algorithm for OTC deficiency. Although the accuracy of prenatal and carrier detection of OTC deficiency has been greatly improved by linkage analysis since the cloning of the gene, RFLP-based diagnosis is limited in this disorder in which many of the cases represent new mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1671317" 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="#94" class="mim-tip-reference" title="Yudkoff, M., Daikhin, Y., Nissim, I., Jawad, A., Wilson, J., Batshaw, M. &lt;strong&gt;In vivo nitrogen metabolism in ornithine transcarbamylase deficiency.&lt;/strong&gt; J. Clin. Invest. 98: 2167-2173, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8903337/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8903337&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI119023&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8903337">Yudkoff et al. (1996)</a> developed a new technique that monitors metabolic competence in female heterozygotes for OTC deficiency. They concluded that the test effectively monitors in vivo nitrogen metabolism and may obviate the need for liver biopsy to measure enzyme activity in OTC deficiency. Asymptomatic OTC deficiency carriers form urea at a normal rate, indicating that ureagenesis can be competent even though enzyme activity is below normal. Although ostensibly asymptomatic OTC deficiency carriers form urea at a normal rate, their nitrogen metabolism is still abnormal, as reflected in their increased production of 5-(15)N-glutamine. The new test may be important for monitoring the efficacy of novel treatments for OTC deficiency, e.g., liver transplantation and gene therapy. The method uses mass spectrometry to measure conversion of (15)NH(4)Cl to (15)N-urea and 5-(15)N-glutamine following an oral load of (15)NH(4)Cl. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8903337" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Bowling, F., McGown, I., McGill, J., Cowley, D., Tuchman, M. &lt;strong&gt;Maternal gonadal mosaicism causing ornithine transcarbamylase deficiency.&lt;/strong&gt; Am. J. Med. Genet. 85: 452-454, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10405441/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10405441&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/(sici)1096-8628(19990827)85:5&lt;452::aid-ajmg4&gt;3.0.co;2-4&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10405441">Bowling et al. (1999)</a> reported a family with 2 consecutive males with OTC deficiency caused by mutation in the OTC gene. The mother had normal biochemical studies. Genotyping of the mother was performed on peripheral blood leukocytes and skin fibroblasts and showed no mutation, strongly suggesting gonadal mosaicism. The authors noted that gonadal mosaicism needs to be considered when counseling couples in which the mother has had a previously affected child with OTC deficiency but does not appear to be a carrier. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10405441" 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="#38" class="mim-tip-reference" title="Iijima, H., Kubota, M. &lt;strong&gt;A simple screening method for heterozygous female patients with ornithine transcarbamylase deficiency.&lt;/strong&gt; Molec. Genet. Metab. 137: 301-307, 2022.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/36252454/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;36252454&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2022.10.003&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="36252454">Iijima and Kubota (2022)</a> demonstrated that the metabolite ratio (glutamine+glycine)/(citrulline+arginine) had a 100% sensitivity and 98% specificity in discriminating 10 female patients with OTC deficiency from 966 patients with other disorders, including cardiac, neurologic, liver, intestinal, and renal diseases. Furthermore, this ratio was significantly higher in females with OTC deficiency when they were acutely ill compared to when they were asymptomatic. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36252454" 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>Prenatal Diagnosis</em></strong></p><p>
In a report of prenatal diagnosis of OTC deficiency, <a href="#66" class="mim-tip-reference" title="Pembrey, M. E., Old, J. M., Leonard, J. V., Rodeck, C. H., Warren, R., Davies, K. E. &lt;strong&gt;Prenatal diagnosis of ornithine carbamoyl transferase deficiency using a gene specific probe.&lt;/strong&gt; J. Med. Genet. 22: 462-465, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3001312/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3001312&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.22.6.462&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3001312">Pembrey et al. (1985)</a> suggested that regardless of the predicted outcome as far as the fetus is concerned, the biochemical status of the carrier mother should be monitored because hyperammonemia and arginine deficiency might have a deleterious effect on the fetus, perhaps particularly if a female fetus is heterozygous for the OTC deficiency gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3001312" 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>Fox et al. (<a href="#20" class="mim-tip-reference" title="Fox, J. E., Hack, A. M., Fenton, W. A., Golbus, M. S., Winter, S., Kalousek, F., Rozen, R., Brusilow, S. W., Rosenberg, L. E. &lt;strong&gt;Prenatal diagnosis of ornithine transcarbamylase deficiency with use of DNA polymorphisms.&lt;/strong&gt; New Eng. J. Med. 315: 1205-1208, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3762643/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3762643&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM198611063151907&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3762643">1986</a>, <a href="#21" class="mim-tip-reference" title="Fox, J. E., Hack, A. M., Fenton, W. A., Rosenberg, L. E. &lt;strong&gt;Identification and application of additional restriction fragment length polymorphisms at the human ornithine transcarbamylase locus.&lt;/strong&gt; Am. J. Hum. Genet. 38: 841-847, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3014867/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3014867&lt;/a&gt;]" pmid="3014867">1986</a>) discussed the use of DNA polymorphisms in the prenatal diagnosis of OTC deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3762643+3014867" 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>Clinical Management</strong>
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<p><a href="#5" class="mim-tip-reference" title="Batshaw, M. L., Brusilow, S., Waber, L., Blom, W., Brubakk, A. M., Burton, B. K., Cann, H. M., Kerr, D., Mamunes, P., Matalon, R., Myerberg, D., Schafer, I. A. &lt;strong&gt;Treatment of inborn errors of urea synthesis: activation of alternative pathways of waste nitrogen synthesis and excretion.&lt;/strong&gt; New Eng. J. Med. 306: 1387-1392, 1982.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7078580/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7078580&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM198206103062303&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7078580">Batshaw et al. (1982)</a> reported on therapy of 26 patients with inborn errors of urea synthesis by activation of alternative pathways of waste nitrogen synthesis and excretion. In 7 with deficiency of argininosuccinate synthetase (citrullinemia) and 10 with deficiency of argininosuccinate lyase (argininosuccinic aciduria), excretion of citrulline and argininosuccinate served as waste nitrogen products because they contain nitrogen normally destined for urea synthesis; synthesis and excretion of these substances was enhanced by arginine supplementation. Administration of sodium benzoate further diverted ammonium nitrogen from the defective urea pathway to hippurate synthesis by way of the glycine cleavage complex in the above 2 disorders, as well as in ornithine transcarbamylase deficiency and hyperammonemia due to carbamoyl phosphate synthetase deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7078580" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Brusilow, S. W., Danney, M., Waber, L. J., Batshaw, M., Burton, B., Levitsky, L., Roth, K., McKeethren, C., Ward, J. &lt;strong&gt;Treatment of episodic hyperammonemia in children with inborn errors of urea synthesis.&lt;/strong&gt; New Eng. J. Med. 310: 1630-1634, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6427608/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6427608&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM198406213102503&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6427608">Brusilow et al. (1984)</a> reported the successful treatment of episodic hyperammonemia in children with carbamoyl phosphate synthetase deficiency, ornithine transcarbamylase deficiency, and citrullinemia. Treatment made use of intravenous sodium benzoate, sodium phenylacetate and arginine, nitrogen-free intravenous alimentation, and, when other measures failed, dialysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6427608" 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="#58" class="mim-tip-reference" title="Michels, V. V., Potts, E., Walser, M., Beaudet, A. L. &lt;strong&gt;Ornithine transcarbamylase deficiency: long-term survival.&lt;/strong&gt; Clin. Genet. 22: 211-214, 1982.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7151305/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7151305&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1399-0004.1982.tb01435.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7151305">Michels et al. (1982)</a> reported survival to over 4 years of age in a male with OTC deficiency who was treated with a very low protein diet supplemented with essential amino acids and keto acid analog of essential amino acids. <a href="#44" class="mim-tip-reference" title="Korson, M. S., Lillehei, C. W., Vacanti, J. P., Levy, H. L. &lt;strong&gt;Liver transplantation for ornithine transcarbamylase deficiency (OTCD). (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 45 (suppl.): A8, 1989."None>Korson et al. (1989)</a> described the successful use of liver transplantation in the treatment of OTC deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7151305" 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="#54" class="mim-tip-reference" title="Maestri, N. E., Hauser, E. R., Bartholomew, D., Brusilow, S. W. &lt;strong&gt;Prospective treatment of urea cycle disorders.&lt;/strong&gt; J. Pediat. 119: 923-928, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1720458/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1720458&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(05)83044-6&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1720458">Maestri et al. (1991)</a> described a diagnostic and therapeutic protocol designed to prevent clinical expression of inborn errors of urea synthesis in the neonatal period. In 7 of 32 affected infants with carbamoyl phosphate synthetase deficiency, argininosuccinate synthetase deficiency, and argininosuccinate lyase deficiency, therapy was effective in avoiding neonatal hyperammonemic coma and death. When treated prospectively, 5 of 8 patients with OTC deficiency avoided severe hyperammonemia and survived the neonatal period. Two of the patients with OTC deficiency subsequently died; 3 others had received orthotopic liver transplants. The experience with all of the surviving patients suggested a more favorable neurologic outcome than that achieved in patients rescued from neonatal hyperammonemic coma. <a href="#53" class="mim-tip-reference" title="Maestri, N. E., Brusilow, S. W., Clissold, D. B., Bassett, S. S. &lt;strong&gt;Long-term treatment of girls with ornithine transcarbamylase deficiency.&lt;/strong&gt; New Eng. J. Med. 335: 855-859, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8778603/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8778603&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM199609193351204&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8778603">Maestri et al. (1996)</a> reported on the long-term outcome of 32 girls with OTC deficiency enrolled in a treatment protocol who had at least 1 episode of encephalopathy. The authors reported a survival rate greater than 90% at 5 years of age. The frequency of hyperammonemic episodes decreased with increasing age and with sodium phenylacetate or sodium phenylbutyrate treatment. Although mean IQ before treatment was in the low average range, 19 of the 23 girls in whom intelligence was tested longitudinally had stable test scores. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1720458+8778603" 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="#92" class="mim-tip-reference" title="Wilson, C. J., Lee, P. J., Leonard, J. V. &lt;strong&gt;Plasma glutamine and ammonia concentrations in ornithine carbamoyltransferase deficiency and citrullinaemia.&lt;/strong&gt; J. Inherit. Metab. Dis. 24: 691-695, 2001.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11804205/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11804205&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1023/a:1012995701589&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11804205">Wilson et al. (2001)</a> reviewed the plasma ammonia and glutamine concentrations during long-term management of 7 patients with OTC deficiency and 3 patients with citrullinemia. Patients with citrullinemia tended to have higher plasma ammonia concentrations for a given plasma glutamine concentration compared to those with OTC deficiency, and there was not a simple linear relationship between glutamine and ammonia in either condition. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11804205" 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="#91" class="mim-tip-reference" title="Wilnai, Y., Blumenfeld, Y. J., Cusmano, K., Hintz, S. R., Alcorn, D., Benitz, W. E., Berquist, W. E., Bernstein, J. A., Castillo, R. O., Concepcion, W., Cowan, T. M., Cox, K. L., and 10 others. &lt;strong&gt;Prenatal treatment of ornithine transcarbamylase deficiency.&lt;/strong&gt; Molec. Genet. Metab. 123: 297-300, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29396029/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;29396029&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2018.01.004&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="29396029">Wilnai et al. (2018)</a> reported perinatal treatment in 2 OTC deficiency carrier mothers with male fetuses who had prenatal diagnoses of OTC. At the start of labor, the mothers were each given a bolus of Ammonul at a dose of 5.5 gm per meter squared body surface area and arginine at a dose of 4 gm per meter squared body surface area, followed by maintenance Ammonul and arginine until delivery. Intravenous dextrose was also given. <a href="#91" class="mim-tip-reference" title="Wilnai, Y., Blumenfeld, Y. J., Cusmano, K., Hintz, S. R., Alcorn, D., Benitz, W. E., Berquist, W. E., Bernstein, J. A., Castillo, R. O., Concepcion, W., Cowan, T. M., Cox, K. L., and 10 others. &lt;strong&gt;Prenatal treatment of ornithine transcarbamylase deficiency.&lt;/strong&gt; Molec. Genet. Metab. 123: 297-300, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29396029/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;29396029&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ymgme.2018.01.004&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="29396029">Wilnai et al. (2018)</a> found that the ammonia, glutamine, and alanine levels were normal in the newborns at birth. The infants were started on intravenous maintenance Ammonul, arginine, dextrose, and electrolytes in the intensive care unit and transitioned to oral sodium phenylbutyrate and citrulline before discharge. Orthotopic liver transplant occurred at age 3 months in one infant and at age 5 months in the other. Development was described as normal in both patients at 7 years and 3 years, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29396029" 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="#84" class="mim-tip-reference" title="Torkzaban, M., Haddad, A., Baxter, J. K., Berghella, V., Gahl, W. A., Al-Kouatly, H. &lt;strong&gt;Maternal ornithine transcarbamylase deficiency, a genetic condition associated with high maternal and neonatal mortality every clinician should know: a systematic review.&lt;/strong&gt; Am. J. Med. Genet. 179A: 2091-2100, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/31441224/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;31441224&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.61329&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="31441224">Torkzaban et al. (2019)</a> discussed recommendations for metabolic management of women with OTC deficiency during and after labor and delivery. They recommended delivery at 39 weeks' gestation to ensure management by a maternal fetal medicine specialist, metabolic dietitian, geneticist, and neonatologist. During labor and delivery, IV fluids with dextrose should be provided to prevent catabolism. Ammonia should be measured every 6 hours during labor and delivery and then for at least 72 hours after. Patients should be given discharge instructions describing the symptoms of hyperammonemia in the postpartum period and to report any of these symptoms to their doctor. <a href="#84" class="mim-tip-reference" title="Torkzaban, M., Haddad, A., Baxter, J. K., Berghella, V., Gahl, W. A., Al-Kouatly, H. &lt;strong&gt;Maternal ornithine transcarbamylase deficiency, a genetic condition associated with high maternal and neonatal mortality every clinician should know: a systematic review.&lt;/strong&gt; Am. J. Med. Genet. 179A: 2091-2100, 2019.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/31441224/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;31441224&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.61329&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="31441224">Torkzaban et al. (2019)</a> also recommended that a dietitian be consulted in the postpartum period with the goal of avoiding both catabolism and protein overload. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31441224" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="molecularGenetics" class="mim-anchor"></a>
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<strong>Molecular Genetics</strong>
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<p><a href="#72" class="mim-tip-reference" title="Rozen, R., Fox, J., Fenton, W. A., Horwich, A. L., Rosenberg, L. E. &lt;strong&gt;Gene deletion and restriction fragment length polymorphisms at the human ornithine transcarbamylase locus.&lt;/strong&gt; Nature 313: 815-817, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2983225/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2983225&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/313815a0&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2983225">Rozen et al. (1985)</a> gave the first reported example of an OTC gene deletion that could be identified cytogenetically in a patient with OTC deficiency. In a boy with a mild form of OTC deficiency, <a href="#51" class="mim-tip-reference" title="Maddalena, A., Sosnoski, D. M., Berry, G. T., Nussbaum, R. L. &lt;strong&gt;Mosaicism for an intragenic deletion in a boy with mild ornithine transcarbamylase deficiency.&lt;/strong&gt; New Eng. J. Med. 319: 999-1003, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2843770/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2843770&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM198810133191507&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2843770">Maddalena et al. (1988)</a> found somatic mosaicism for an intragenic deletion of the OTC gene (<a href="/entry/300461#0001">300461.0001</a>). In 3 of 24 unrelated patients with OTC deficiency, <a href="#52" class="mim-tip-reference" title="Maddalena, A., Spence, J. E., O&#x27;Brien, W. E., Nussbaum, R. L. &lt;strong&gt;Characterization of point mutations in the same arginine codon in three unrelated patients with ornithine transcarbamylase deficiency.&lt;/strong&gt; J. Clin. Invest. 82: 1353-1358, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3170748/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3170748&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI113738&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3170748">Maddalena et al. (1988)</a> identified 2 different point mutations in the same codon of the OTC gene (<a href="/entry/300461#0002">300461.0002</a>-<a href="/entry/300461#0003">300461.0003</a>). The patients included 2 males with severe neonatal onset and a female patient with mild disease. In 5 unrelated patients with OTC deficiency, <a href="#26" class="mim-tip-reference" title="Grompe, M., Muzny, D. M., Caskey, C. T. &lt;strong&gt;Scanning detections of mutations in human ornithine transcarbamylase deficiency (OTC) by chemical mismatch cleavage. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 45 (suppl.): A192, 1989."None>Grompe et al. (1989)</a> identified 4 mutations and a polymorphism in the OTC gene (<a href="/entry/300461#0004">300461.0004</a>-<a href="/entry/300461#0009">300461.0009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2983225+3170748+2843770" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a catalog of mutations in the OTC gene, <a href="#87" class="mim-tip-reference" title="Tuchman, M. &lt;strong&gt;Mutations and polymorphisms in the human ornithine transcarbamylase gene.&lt;/strong&gt; Hum. Mutat. 2: 174-178, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8364586/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8364586&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.1380020304&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8364586">Tuchman (1993)</a> reported that approximately 10 to 15% of all molecular alterations associated with OTC deficiency were large deletions involving all or part of the OTC gene. <a href="#86" class="mim-tip-reference" title="Tuchman, M., Plante, R. J., Garcia-Perez, M. A., Rubio, V. &lt;strong&gt;Relative frequency of mutations causing ornithine transcarbamylase deficiency in 78 families.&lt;/strong&gt; Hum. Genet. 97: 274-276, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8786061/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8786061&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF02185751&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8786061">Tuchman et al. (1996)</a> estimated that approximately 90 different mutations associated with OTC deficiency had been defined. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8364586+8786061" 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="#39" class="mim-tip-reference" title="Jang, Y. J., LaBella, A. L., Feeney, T. P., Braverman, N., Tuchman, M., Morizono, H., Ah Mew, N., Caldovic, L. &lt;strong&gt;Disease-causing mutations in the promoter and enhancer of the ornithine transcarbamylase gene.&lt;/strong&gt; Hum. Mutat. 39: 527-536, 2018.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/29282796/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;29282796&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=29282796[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.23394&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="29282796">Jang et al. (2018)</a> identified promoter or enhancer mutations of the OTC gene in 9 patients with a clinical diagnosis of OTC deficiency but without identifiable mutations in the exons and exon/intron boundaries of the OTC gene. Six mutations in the OTC promoter (c.-106C-A, c.-115C-T, c.-116C-T, c.-106C-A, c.-115C-T, c.-116C-T) were identified in patients 1-8, and 1 mutation in an OTC enhancer (c.-9384G-T) was identified in patient 9. Using a dual luciferase assay to establish effects on gene expression, the authors found that each of the promoter mutations as well as the enhancer mutation resulted in reduction of luciferase activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29282796" 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="#50" class="mim-tip-reference" title="Lopes-Marques, M., Pacheco, A. R., Peixoto, M. J., Cardoso, A. R., Serrano, C., Amorim, A., Prata, M. J., Cooper, D. N., Azevedo, L. &lt;strong&gt;Common polymorphic OTC variants can act as genetic modifiers of enzymatic activity.&lt;/strong&gt; Hum. Mutat. 42: 978-989, 2021.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/34015158/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;34015158&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=34015158[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/humu.24221&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="34015158">Lopes-Marques et al. (2021)</a> evaluated the role of 2 polymorphisms in the OTC gene, K46R and Q270R, on the function of wildtype OTC and OTC with the known pathogenic mutation R40H (<a href="/entry/300461#0029">300461.0029</a>) in HEK293 cells. The combination of both polymorphisms resulted in a significant increase in OTC enzyme function, whereas only the Q270R polymorphism resulted in a significant increase in OTC enzyme activity in cis with the R40H mutation. Structural analysis suggested that the Q270R polymorphism stabilized OTC with the R40H mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34015158" 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="#49" class="mim-tip-reference" title="Lo, R. S., Cromie, G. A., Tang, M., Teng, K., Owens, K., Sirr, A., Kutz, J. N., Morizono, H., Caldovic, L., Ah Mew, N., Gropman, A., Dudley, A. M. &lt;strong&gt;The functional impact of 1,570 individual amino acid substitutions in human OTC.&lt;/strong&gt; Am. J. Hum. Genet. 110: 863-879, 2023.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/37146589/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;37146589&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.ajhg.2023.03.019&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="37146589">Lo et al. (2023)</a> developed a yeast growth-based assay to evaluate the function of OTC with each of 1,570 amino acid substitutions, which represented 84% of the missense mutations that were potentially caused by single nucleotide substitutions in the OTC gene. Residual growth values were used to categorize the mutations into functionally unimpaired (greater than 90% residual growth), functionally hypomorphic (5-90% residual growth), or functionally amorphic (less than 5% residual growth). Correlations were identified between the residual growth values and disease severity, relative conservation, and functional gene regions. The exception to this was the 13-amino acid SMG loop of OTC, which appeared to be functionally relevant in human cells but not in yeast cells. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=37146589" 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>X Inactivation</em></strong></p><p>
To understand the correlation between X-inactivation status and the clinical phenotype of carrier females (which can vary from asymptomatic to severe hyperammonemia), <a href="#93" class="mim-tip-reference" title="Yorifuji, T., Muroi, J., Uematsu, A., Tanaka, K., Kiwaki, K., Endo, F., Matsuda, I., Nagasaka, H., Furusho, K. &lt;strong&gt;X-inactivation pattern in the liver of a manifesting female with ornithine transcarbamylase (OTC) deficiency.&lt;/strong&gt; Clin. Genet. 54: 349-353, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9831349/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9831349&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1034/j.1399-0004.1998.5440415.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9831349">Yorifuji et al. (1998)</a> analyzed the X-inactivation pattern of peripheral blood leukocytes in a family consisting of a clinically normal mother and 2 daughters with a severe manifestation. In addition, they obtained tissue samples from various parts of the liver of one of the daughters and analyzed X-inactivation patterns and residual OTC activities. The X inactivation of peripheral blood leukocytes was nearly random in these carrier females and showed no correlation with the disease phenotype; however, the X inactivation of the liver was much more skewed and correlated well with the OTC activity of all samples. The degree of X inactivation varied considerably, even within the same liver. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9831349" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="genotypePhenotypeCorrelations" class="mim-anchor"></a>
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<p><a href="#57" class="mim-tip-reference" title="McCullough, B. A., Yudkoff, M., Batshaw, M. L., Wilson, J. M., Raper, S. E., Tuchman, M. &lt;strong&gt;Genotype spectrum of ornithine transcarbamylase deficiency: correlation with the clinical and biochemical phenotype.&lt;/strong&gt; Am. J. Med. Genet. 93: 313-319, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10946359/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10946359&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/1096-8628(20000814)93:4&lt;313::aid-ajmg11&gt;3.0.co;2-m&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10946359">McCullough et al. (2000)</a> examined the genotype/phenotype correlations of 157 probands with OTC deficiency, including 57 heterozygous females. In patients with mutations that abolished enzyme activity, the severe clinical and biochemical phenotype was homogeneous. The males in this group presented within the first few days of life with high mortality and morbidity. Most patients with the late-onset form had missense mutations in the OTC gene, although a few had 3-bp deletions, and late-onset patients had residual enzyme activity ranging from 26 to 74% of normal control values. Mutations in manifesting females were primarily of the neonatal-onset type. Substitutions occurring in CpG dinucleotides accounted for approximately 31% of all mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10946359" 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>Population Genetics</strong>
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<p><a href="#60" class="mim-tip-reference" title="Nagata, N., Matsuda, I., Oyanagi, K. &lt;strong&gt;Estimated frequency of urea cycle enzymopathies in Japan. (Letter)&lt;/strong&gt; Am. J. Med. Genet. 39: 228-229, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2063931/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2063931&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320390226&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2063931">Nagata et al. (1991)</a> estimated that OTC deficiency has a frequency of 1 in 80,000 births in Japan. The total frequency of this and the other urea cycle enzymopathies, carbamoyl phosphate synthetase deficiency, argininosuccinate synthetase deficiency, argininosuccinate lyase deficiency, and arginase deficiency, in Japan was 1 in 46,000. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2063931" 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="#82" class="mim-tip-reference" title="Testai, F. D., Gorelick, P. B. &lt;strong&gt;Inherited metabolic disorders and stroke part 2: homocystinuria, organic acidurias, and urea cycle disorders.&lt;/strong&gt; Arch. Neurol. 67: 148-153, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20142522/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20142522&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1001/archneurol.2009.333&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20142522">Testai and Gorelick (2010)</a> estimated the prevalence of OTC to range from 1 in 40,000 to 1 in 80,000. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20142522" 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>Animal Model</strong>
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<p>The trait 'sparse fur' (spf) in the mouse is due to OTC deficiency. X-linkage was confirmed indirectly by the demonstration of <a href="#16" class="mim-tip-reference" title="DeMars, R., LeVan, S. L., Trend, B. L., Russell, L. B. &lt;strong&gt;Abnormal ornithine carbamyltransferase in mice having the sparse-fur mutation.&lt;/strong&gt; Proc. Nat. Acad. Sci. 73: 1693-1697, 1976.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5727/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5727&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.73.5.1693&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="5727">DeMars et al. (1976)</a> that the same enzyme deficiency is X-linked in the mouse. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5727" 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>Extracts of liver from hemizygous affected mice with the X-linked spf(ash) (sparse fur, abnormal skin and hair) mutation have 5 to 10% of normal OTC activity, yet the homogeneous enzyme isolated from these extracts is identical to that in controls. <a href="#70" class="mim-tip-reference" title="Rosenberg, L. E., Kalousek, F., Orsulak, M. D. &lt;strong&gt;Biogenesis of ornithine transcarbamylase in spf(ash) mutant mice: two cytoplasmic precursors, one mitochondrial enzyme.&lt;/strong&gt; Science 222: 426-428, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6623083/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6623083&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1126/science.6623083&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6623083">Rosenberg et al. (1983)</a> found that the mRNA from mutant livers programs the synthesis of 2 distinct OTC precursor polypeptides: one normal in size, the other elongated. Only the normal one is assembled into the active trimeric enzyme. The novel phenotype likely results from a mutation in the structural gene for OTC, leading to aberrant splicing of mRNA and formation of an altered precursor that cannot undergo proper posttranslational modification. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6623083" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In the 'sparse fur' mouse, <a href="#88" class="mim-tip-reference" title="Veres, G., Gibbs, R. A., Scherer, S. E., Caskey, C. T. &lt;strong&gt;The molecular basis of the sparse fur mouse mutation.&lt;/strong&gt; Science 237: 415-417, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3603027/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3603027&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1126/science.3603027&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3603027">Veres et al. (1987)</a> identified a mutation in the OTC gene (see also <a href="#62" class="mim-tip-reference" title="Ohtake, A., Takayanagi, M., Yamamoto, S., Kakinuma, H., Nakajima, H., Tatibana, M., Mori, M. &lt;strong&gt;Molecular basis of ornithine transcarbamylase deficiency in spf and spf-ash mutant mice.&lt;/strong&gt; J. Inherit. Metab. Dis. 9: 289-291, 1986.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3099076/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3099076&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF01799667&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3099076">Ohtake et al., 1986</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=3099076+3603027" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Cavard, C., Grimber, G., Dubois, N., Chasse, J.-F., Bennoun, M., Minet-Thuriaux, M., Kamoun, P., Briand, P. &lt;strong&gt;Correction of mouse ornithine transcarbamylase deficiency by gene transfer into the germ line.&lt;/strong&gt; Nucleic Acids Res. 16: 2099-2110, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3162766/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3162766&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1093/nar/16.5.2099&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3162766">Cavard et al. (1988)</a> successfully corrected OTC deficiency in the mouse by injection of rat OTC cDNA linked to the SV40 early promoter into fertilized eggs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3162766" 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="#59" class="mim-tip-reference" title="Morsy, M. A., Zhao, J. Z., Ngo, T. T., Warman, A. W., O&#x27;Brien, W. E., Graham, F. L., Caskey, C. T. &lt;strong&gt;Patient selection may affect gene therapy success: dominant negative effects observed for ornithine transcarbamylase in mouse and human hepatocytes.&lt;/strong&gt; J. Clin. Invest. 97: 826-832, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8609240/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8609240&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI118482&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8609240">Morsy et al. (1996)</a> achieved significant improvement of OTC deficiency in a mouse model through adenovirus-mediated gene transfer of the human OTC cDNA. Substantial reduction in orotic aciduria was observed within 24 hours of treatment. Metabolic correction was later associated with phenotypic correction and moderate increase in enzymatic activity. In an effort to identify the level of gene expression required to achieve wildtype levels of enzyme activity, <a href="#59" class="mim-tip-reference" title="Morsy, M. A., Zhao, J. Z., Ngo, T. T., Warman, A. W., O&#x27;Brien, W. E., Graham, F. L., Caskey, C. T. &lt;strong&gt;Patient selection may affect gene therapy success: dominant negative effects observed for ornithine transcarbamylase in mouse and human hepatocytes.&lt;/strong&gt; J. Clin. Invest. 97: 826-832, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8609240/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8609240&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI118482&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8609240">Morsy et al. (1996)</a> uncovered a dominant-negative effect of the endogenous mutant protein on the activity of the delivered recombinant wildtype protein. The authors stated that this phenomenon is relevant to homomultimeric protein defects, such as OTC deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8609240" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="seeAlso" class="mim-anchor"></a>
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<span class="mim-font">
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<strong>See Also:</strong>
</span>
</h4>
<div id="mimSeeAlsoFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<a href="#Amir1982" class="mim-tip-reference" title="Amir, J., Alpert, G., Statter, M., Gutman, A., Reisner, S. H. &lt;strong&gt;Intracranial haemorrhage in siblings and ornithine transcarbamylase deficiency.&lt;/strong&gt; Acta Paediat. Scand. 71: 671-673, 1982.">Amir et al. (1982)</a>; <a href="#Batshaw1980" class="mim-tip-reference" title="Batshaw, M. L., Roan, Y., Jung, A. L., Rosenberg, L. A., Brusilow, S. W. &lt;strong&gt;Cerebral dysfunction in asymptomatic carriers of ornithine transcarbamylase deficiency.&lt;/strong&gt; New Eng. J. Med. 302: 482-485, 1980.">Batshaw et al. (1980)</a>; <a href="#Cathelineau1974" class="mim-tip-reference" title="Cathelineau, L., Saudubray, J.-M., Polonovski, C. &lt;strong&gt;Heterogeneous mutations of the structural gene of human ornithine carbamyltransferase as observed in five personal cases.&lt;/strong&gt; Enzyme 18: 103-113, 1974.">Cathelineau et al. (1974)</a>; <a href="#Gelehrter1975" class="mim-tip-reference" title="Gelehrter, T. D., Rosenberg, L. E. &lt;strong&gt;Ornithine transcarbamylase deficiency: unsuccessful therapy of neonatal hyperammonemia with N-carbamyl-L-glutamate and L-arginine.&lt;/strong&gt; New Eng. J. Med. 292: 351-352, 1975.">Gelehrter and Rosenberg (1975)</a>; <a href="#Harding1984" class="mim-tip-reference" title="Harding, B. N., Leonard, J. V., Erdohazi, M. &lt;strong&gt;Ornithine carbamoyl transferase deficiency: a neuropathological study.&lt;/strong&gt; Europ. J. Pediat. 141: 215-220, 1984.">Harding et al. (1984)</a>; <a href="#Herrin1969" class="mim-tip-reference" title="Herrin, J. T., McCredie, D. A. &lt;strong&gt;Peritoneal dialysis in the reduction of blood ammonia levels in a case of hyperammonaemia.&lt;/strong&gt; Arch. Dis. Child. 44: 149-151, 1969.">Herrin and
McCredie (1969)</a>; <a href="#Hokanson1978" class="mim-tip-reference" title="Hokanson, J. T., O&#x27;Brien, W. E., Idemoto, J., Schafer, I. A. &lt;strong&gt;Carrier detection in ornithine transcarbamylase deficiency.&lt;/strong&gt; J. Pediat. 93: 75-78, 1978.">Hokanson et al. (1978)</a>; <a href="#Holzgreve1984" class="mim-tip-reference" title="Holzgreve, W., Golbus, M. S. &lt;strong&gt;Prenatal diagnosis of ornithine transcarbamylase deficiency utilizing fetal liver biopsy.&lt;/strong&gt; Am. J. Hum. Genet. 36: 320-328, 1984.">Holzgreve and Golbus (1984)</a>; <a href="#Hoogenraad1983" class="mim-tip-reference" title="Hoogenraad, N., de Martinis, M. L., Danks, D. M. &lt;strong&gt;Immunological evidence for an ornithine transcarbamylase lesion resulting in the formation of enzyme with smaller protein subunits.&lt;/strong&gt; J. Inherit. Metab. Dis. 6: 149-152, 1983.">Hoogenraad et al. (1983)</a>; <a href="#Hopkins1969" class="mim-tip-reference" title="Hopkins, I. J., Connelly, J. F., Dawson, A. G., Hird, F. J., Maddison, T. G. &lt;strong&gt;Hyperammonaemia due to ornithine transcarbamylase deficiency.&lt;/strong&gt; Arch. Dis. Child. 44: 143-148, 1969.">Hopkins et al. (1969)</a>; <a href="#Kodama1986" class="mim-tip-reference" title="Kodama, H., Ohtake, A., Mori, M., Okabe, I., Tatibana, M., Kamoshita, S. &lt;strong&gt;Ornithine transcarbamylase deficiency: a case with a truncated enzyme precursor and a case with undetectable mRNA activity.&lt;/strong&gt; J. Inherit. Metab. Dis. 9: 175-185, 1986.">Kodama et al.
(1986)</a>; <a href="#Nussbaum1986" class="mim-tip-reference" title="Nussbaum, R. L., Boggs, B. A., Beaudet, A. L., Doyle, S., Potter, J. L., O&#x27;Brien, W. E. &lt;strong&gt;New mutation and prenatal diagnosis in ornithine transcarbamylase deficiency.&lt;/strong&gt; Am. J. Hum. Genet. 38: 149-158, 1986.">Nussbaum et al. (1986)</a>; <a href="#Old1985" class="mim-tip-reference" title="Old, J. M., Briand, P. L., Purvis-Smith, S., Howard, N. J., Wilcken, B., Hammond, J., Pearson, P., Cathelineau, L., Williamson, R., Davies, K. E. &lt;strong&gt;Prenatal exclusion of ornithine transcarbamylase deficiency by direct gene analysis.&lt;/strong&gt; Lancet 325: 73-75, 1985. Note: Originally Volume I.">Old et al. (1985)</a>; <a href="#Qureshi1979" class="mim-tip-reference" title="Qureshi, I. A., Letarte, J., Ouellet, R. &lt;strong&gt;Ornithine transcarbamylase deficiency in mutant mice. I. Studies on the characterization of enzyme defect and suitability as animal model of human disease.&lt;/strong&gt; Pediat. Res. 13: 807-811, 1979.">Qureshi et al.
(1979)</a>; <a href="#Rodeck1982" class="mim-tip-reference" title="Rodeck, C. H., Patrick, A. D., Pembrey, M. E., Tzannatos, C., Whitfield, A. E. &lt;strong&gt;Fetal liver biopsy for prenatal diagnosis of ornithine carbamyl transferase deficiency.&lt;/strong&gt; Lancet 320: 297-300, 1982. Note: Originally Volume II.">Rodeck et al. (1982)</a>; <a href="#Schwartz1986" class="mim-tip-reference" title="Schwartz, M., Christensen, E., Christensen, N. C., Skovby, F., Davies, K. E., Old, J. M. &lt;strong&gt;Detection and exclusion of carriers of ornithine transcarbamylase deficiency by RFLP analysis.&lt;/strong&gt; Clin. Genet. 29: 449-452, 1986.">Schwartz et al. (1986)</a>; <a href="#Shapiro1980" class="mim-tip-reference" title="Shapiro, J. M., Schaffner, F., Tallan, H. H., Gaull, G. E. &lt;strong&gt;Mitochondrial abnormalities of liver in primary ornithine transcarbamylase deficiency.&lt;/strong&gt; Pediat. Res. 14: 735-759, 1980.">Shapiro et al.
(1980)</a>; <a href="#Shih1978" class="mim-tip-reference" title="Shih, V. E., Berson, E. L., Mandell, R., Schmidt, S. Y. &lt;strong&gt;Ornithine ketoacid transaminase deficiency in gyrate atrophy of the choroid and retina.&lt;/strong&gt; Am. J. Hum. Genet. 30: 174-179, 1978.">Shih et al. (1978)</a>; <a href="#Snodgrass1978" class="mim-tip-reference" title="Snodgrass, P. J., Wappner, R. S., Brandt, I. K. &lt;strong&gt;White cell ornithine transcarbamylase activity cannot detect the liver enzyme deficiency. (Letter)&lt;/strong&gt; Pediat. Res. 12: 873, 1978.">Snodgrass et al. (1978)</a>; <a href="#Stoll1978" class="mim-tip-reference" title="Stoll, C., Bieth, R., Dreyfus, J., Flori, E., Lutz, P., Levy, J.-M. &lt;strong&gt;Une nouvelle famille avec mutation du gene de structure de l&#x27;ornithine carbamyltransferase humaine.&lt;/strong&gt; Arch. Franc. Pediat. 35: 512-518, 1978.">Stoll et al.
(1978)</a>; <a href="#Sunshine1972" class="mim-tip-reference" title="Sunshine, P., Lindenbaum, J. E., Levy, H. L., Freeman, J. M. &lt;strong&gt;Hyperammonemia due to a defect in hepatic ornithine transcarbamylase.&lt;/strong&gt; Pediatrics 50: 100-111, 1972.">Sunshine et al. (1972)</a>; <a href="#Wareham1987" class="mim-tip-reference" title="Wareham, K. A., Lyon, M. F., Glenister, P. H., Williams, E. D. &lt;strong&gt;Age related reactivation of an X-linked gene.&lt;/strong&gt; Nature 327: 725-727, 1987.">Wareham et al. (1987)</a>; <a href="#Wettke-Schafer1983" class="mim-tip-reference" title="Wettke-Schafer, R., Kantner, G. &lt;strong&gt;X-linked dominant inherited diseases with lethality in hemizygous males.&lt;/strong&gt; Hum. Genet. 64: 1-23, 1983.">Wettke-Schafer
and Kantner (1983)</a>; <a href="#Yudkoff1980" class="mim-tip-reference" title="Yudkoff, M., Yang, W., Snodgrass, P. J., Segal, S. &lt;strong&gt;Ornithine transcarbamylase deficiency in a boy with normal development.&lt;/strong&gt; J. Pediat. 96: 441-443, 1980.">Yudkoff et al. (1980)</a>
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</div>
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</div>
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<h4 href="#mimReferencesFold" id="mimReferencesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span class="mim-font">
<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div id="mimReferencesFold" class="collapse in mimTextToggleFold">
<ol>
<li>
<a id="1" class="mim-anchor"></a>
<a id="Amir1982" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Amir, J., Alpert, G., Statter, M., Gutman, A., Reisner, S. H.
<strong>Intracranial haemorrhage in siblings and ornithine transcarbamylase deficiency.</strong>
Acta Paediat. Scand. 71: 671-673, 1982.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7136688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7136688</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7136688" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1651-2227.1982.tb09497.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="2" class="mim-anchor"></a>
<a id="Anadiotis2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Anadiotis, G., Ierardi-Curto, L., Kaplan, P. B., Berry, G. T.
<strong>Ornithine transcarbamylase deficiency and pancreatitis.</strong>
J. Pediat. 138: 123-124, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11148526/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11148526</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11148526" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1067/mpd.2001.109792" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="3" class="mim-anchor"></a>
<a id="Arn1990" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Arn, P. H., Hauser, E. R., Thomas, G. H., Herman, G., Hess, D., Brusilow, S. W.
<strong>Hyperammonemia in women with a mutation at the ornithine carbamoyltransferase locus: a cause of postpartum coma.</strong>
New Eng. J. Med. 322: 1652-1655, 1990.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2342525/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2342525</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2342525" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM199006073222307" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="4" class="mim-anchor"></a>
<a id="Arn1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Arn, P., Hauser, B., Maestri, N., Herman, G., Thomas, G. H., Brusilow, S. W.
<strong>Hyperammonemic coma in adult females heterozygous at the ornithine transcarbamylase locus (OTCDH). (Abstract)</strong>
Am. J. Hum. Genet. 45 (suppl.): A3, 1989.
</p>
</div>
</li>
<li>
<a id="5" class="mim-anchor"></a>
<a id="Batshaw1982" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Batshaw, M. L., Brusilow, S., Waber, L., Blom, W., Brubakk, A. M., Burton, B. K., Cann, H. M., Kerr, D., Mamunes, P., Matalon, R., Myerberg, D., Schafer, I. A.
<strong>Treatment of inborn errors of urea synthesis: activation of alternative pathways of waste nitrogen synthesis and excretion.</strong>
New Eng. J. Med. 306: 1387-1392, 1982.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7078580/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7078580</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7078580" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM198206103062303" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="6" class="mim-anchor"></a>
<a id="Batshaw1980" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Batshaw, M. L., Roan, Y., Jung, A. L., Rosenberg, L. A., Brusilow, S. W.
<strong>Cerebral dysfunction in asymptomatic carriers of ornithine transcarbamylase deficiency.</strong>
New Eng. J. Med. 302: 482-485, 1980.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7351973/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7351973</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7351973" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM198002283020902" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="7" class="mim-anchor"></a>
<a id="Batshaw2014" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
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://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25135652" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.ymgme.2014.08.001" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="8" class="mim-anchor"></a>
<a id="Bowling1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bowling, F., McGown, I., McGill, J., Cowley, D., Tuchman, M.
<strong>Maternal gonadal mosaicism causing ornithine transcarbamylase deficiency.</strong>
Am. J. Med. Genet. 85: 452-454, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10405441/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10405441</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10405441" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/(sici)1096-8628(19990827)85:5&lt;452::aid-ajmg4&gt;3.0.co;2-4" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="9" class="mim-anchor"></a>
<a id="Brusilow1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Brusilow, S. W., Danney, M., Waber, L. J., Batshaw, M., Burton, B., Levitsky, L., Roth, K., McKeethren, C., Ward, J.
<strong>Treatment of episodic hyperammonemia in children with inborn errors of urea synthesis.</strong>
New Eng. J. Med. 310: 1630-1634, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6427608/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6427608</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6427608" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM198406213102503" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="10" class="mim-anchor"></a>
<a id="Bruton1970" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bruton, C. J., Corsellis, J. A. N., Russell, A.
<strong>Hereditary hyperammonemia.</strong>
Brain 93: 423-434, 1970.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5310321/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5310321</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5310321" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/brain/93.2.423" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="11" class="mim-anchor"></a>
<a id="Burdakin1981" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Burdakin, J. H., Norum, R. A.
<strong>Recombination between loci for ornithine transcarbamylase (OTC) deficiency and G6PD. (Abstract)</strong>
Am. J. Hum. Genet. 33: 38A, 1981.
</p>
</div>
</li>
<li>
<a id="12" class="mim-anchor"></a>
<a id="Campbell1971" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Campbell, A. G. M., Rosenberg, L. E., Snodgrass, P. J., Nuzum, C. T.
<strong>Lethal neonatal hyperammonaemia due to complete ornithine-transcarbamylase deficiency. (Letter)</strong>
Lancet 298: 217-218, 1971. Note: Originally Volume II.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4104881/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4104881</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4104881" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0140-6736(71)90931-7" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="13" class="mim-anchor"></a>
<a id="Campbell1973" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Campbell, A. G. M., Rosenberg, L. E., Snodgrass, P. J., Nuzum, C. T.
<strong>Ornithine transcarbamylase deficiency: a cause of lethal neonatal hyperammonemia in males.</strong>
New Eng. J. Med. 288: 1-6, 1973.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4681895/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4681895</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4681895" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM197301042880101" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="14" class="mim-anchor"></a>
<a id="Cathelineau1974" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Cathelineau, L., Saudubray, J.-M., Polonovski, C.
<strong>Heterogeneous mutations of the structural gene of human ornithine carbamyltransferase as observed in five personal cases.</strong>
Enzyme 18: 103-113, 1974.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4852265/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4852265</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4852265" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1159/000459417" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="15" class="mim-anchor"></a>
<a id="Cavard1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Cavard, C., Grimber, G., Dubois, N., Chasse, J.-F., Bennoun, M., Minet-Thuriaux, M., Kamoun, P., Briand, P.
<strong>Correction of mouse ornithine transcarbamylase deficiency by gene transfer into the germ line.</strong>
Nucleic Acids Res. 16: 2099-2110, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3162766/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3162766</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3162766" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1093/nar/16.5.2099" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="16" class="mim-anchor"></a>
<a id="DeMars1976" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
DeMars, R., LeVan, S. L., Trend, B. L., Russell, L. B.
<strong>Abnormal ornithine carbamyltransferase in mice having the sparse-fur mutation.</strong>
Proc. Nat. Acad. Sci. 73: 1693-1697, 1976.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5727/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5727</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5727" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1073/pnas.73.5.1693" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="17" class="mim-anchor"></a>
<a id="Drogari1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Drogari, E., Leonard, J. V.
<strong>Late onset ornithine carbamoyl transferase deficiency in males.</strong>
Arch. Dis. Child. 63: 1363-1367, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3202644/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3202644</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3202644" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/adc.63.11.1363" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="18" class="mim-anchor"></a>
<a id="Finkelstein1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Finkelstein, J. E., Hauser, E., Brusilow, S. W.
<strong>Late onset ornithine transcarbamylase deficiency (OTCD) in males. (Abstract)</strong>
Am. J. Hum. Genet. 45 (suppl.): A5, 1989.
</p>
</div>
</li>
<li>
<a id="19" class="mim-anchor"></a>
<a id="Finkelstein1990" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Finkelstein, J. E., Hauser, E. R., Leonard, C. O., Brusilow, S. W.
<strong>Late-onset ornithine transcarbamylase deficiency in male patients.</strong>
J. Pediat. 117: 897-902, 1990. Note: Erratum: J. Pediat. 118: 326 only, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2246687/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2246687</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2246687" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0022-3476(05)80129-5" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="20" class="mim-anchor"></a>
<a id="Fox1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Fox, J. E., Hack, A. M., Fenton, W. A., Golbus, M. S., Winter, S., Kalousek, F., Rozen, R., Brusilow, S. W., Rosenberg, L. E.
<strong>Prenatal diagnosis of ornithine transcarbamylase deficiency with use of DNA polymorphisms.</strong>
New Eng. J. Med. 315: 1205-1208, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3762643/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3762643</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3762643" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM198611063151907" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="21" class="mim-anchor"></a>
<a id="Fox1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Fox, J. E., Hack, A. M., Fenton, W. A., Rosenberg, L. E.
<strong>Identification and application of additional restriction fragment length polymorphisms at the human ornithine transcarbamylase locus.</strong>
Am. J. Hum. Genet. 38: 841-847, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3014867/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3014867</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3014867" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="22" class="mim-anchor"></a>
<a id="Gelehrter1975" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gelehrter, T. D., Rosenberg, L. E.
<strong>Ornithine transcarbamylase deficiency: unsuccessful therapy of neonatal hyperammonemia with N-carbamyl-L-glutamate and L-arginine.</strong>
New Eng. J. Med. 292: 351-352, 1975.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1117963/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1117963</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1117963" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM197502132920708" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="23" class="mim-anchor"></a>
<a id="Gilchrist1987" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Gilchrist, J. M., Coleman, R. A.
<strong>Ornithine transcarbamylase deficiency: adult onset of severe symptoms.</strong>
Ann. Intern. Med. 106: 556-558, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3826955/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3826955</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3826955" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.7326/0003-4819-106-4-556" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="24" class="mim-anchor"></a>
<a id="Goldblum1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Goldblum, O. M., Brusilow, S. W., Maldonado, Y. A., Farmer, E. R.
<strong>Neonatal citrullinemia associated with cutaneous manifestations and arginine deficiency.</strong>
J. Am. Acad. Derm. 14: 321-326, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3950131/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3950131</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3950131" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0190-9622(86)70035-2" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="25" class="mim-anchor"></a>
<a id="Grompe1991" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Grompe, M., Caskey, C. T., Fenwick, R. G.
<strong>Improved molecular diagnostics for ornithine transcarbamylase deficiency.</strong>
Am. J. Hum. Genet. 48: 212-222, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1671317/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1671317</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1671317" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="26" class="mim-anchor"></a>
<a id="Grompe1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Grompe, M., Muzny, D. M., Caskey, C. T.
<strong>Scanning detections of mutations in human ornithine transcarbamylase deficiency (OTC) by chemical mismatch cleavage. (Abstract)</strong>
Am. J. Hum. Genet. 45 (suppl.): A192, 1989.
</p>
</div>
</li>
<li>
<a id="27" class="mim-anchor"></a>
<a id="Hamano1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hamano, Y., Kodama, H., Fujikawa, Y., Tanaka, Y., Nishimura, K., Yanagisawa, M.
<strong>Use of immunocytochemical analysis of a duodenal biopsy specimen to identify a carrier of ornithine transcarbamylase deficiency.</strong>
New Eng. J. Med. 318: 1521-1523, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3367962/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3367962</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3367962" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM198806093182307" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="28" class="mim-anchor"></a>
<a id="Harding1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Harding, B. N., Leonard, J. V., Erdohazi, M.
<strong>Ornithine carbamoyl transferase deficiency: a neuropathological study.</strong>
Europ. J. Pediat. 141: 215-220, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6734670/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6734670</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6734670" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF00572763" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="29" class="mim-anchor"></a>
<a id="Hauser1990" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hauser, E. R., Finkelstein, J. E., Valle, D., Brusilow, S. W.
<strong>Allopurinol-induced orotidinuria: a test for mutations at the ornithine carbamoyltransferase locus in women.</strong>
New Eng. J. Med. 322: 1641-1645, 1990. Note: Erratum: New Eng. J. Med. 336: 1335 only, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2342523/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2342523</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2342523" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="30" class="mim-anchor"></a>
<a id="Herrin1969" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Herrin, J. T., McCredie, D. A.
<strong>Peritoneal dialysis in the reduction of blood ammonia levels in a case of hyperammonaemia.</strong>
Arch. Dis. Child. 44: 149-151, 1969.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5779425/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5779425</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5779425" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/adc.44.234.149" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="31" class="mim-anchor"></a>
<a id="Hjelm1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hjelm, M., de Silva, L. V. K., Seakins, J. W. T., Oberholzer, V. G., Rolles, C. J.
<strong>Evidence of inherited urea cycle defect in a case of fatal valproate toxicity.</strong>
Brit. Med. J. 292: 23-24, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3080051/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3080051</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3080051" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/bmj.292.6512.23" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="32" class="mim-anchor"></a>
<a id="Hokanson1978" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hokanson, J. T., O'Brien, W. E., Idemoto, J., Schafer, I. A.
<strong>Carrier detection in ornithine transcarbamylase deficiency.</strong>
J. Pediat. 93: 75-78, 1978.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/650350/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">650350</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=650350" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0022-3476(78)80606-4" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="33" class="mim-anchor"></a>
<a id="Holmes1987" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Holmes, A. K., Fowler, B., Sardharwalla, I. B.
<strong>Late-onset ornithine carbamyl transferase deficiency in a male patient: detailed enzyme studies.</strong>
J. Inherit. Metab. Dis. 10 (suppl. 2): 299-301, 1987.
</p>
</div>
</li>
<li>
<a id="34" class="mim-anchor"></a>
<a id="Holzgreve1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Holzgreve, W., Golbus, M. S.
<strong>Prenatal diagnosis of ornithine transcarbamylase deficiency utilizing fetal liver biopsy.</strong>
Am. J. Hum. Genet. 36: 320-328, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6711559/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6711559</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6711559" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="35" class="mim-anchor"></a>
<a id="Honeycutt1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Honeycutt, D., Callahan, K., Rutledge, L., Evans, B.
<strong>Heterozygote ornithine transcarbamylase deficiency presenting as symptomatic hyperammonemia during initiation of valproate therapy.</strong>
Neurology 42: 666-668, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1549234/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1549234</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1549234" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1212/wnl.42.3.666" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="36" class="mim-anchor"></a>
<a id="Hoogenraad1983" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hoogenraad, N., de Martinis, M. L., Danks, D. M.
<strong>Immunological evidence for an ornithine transcarbamylase lesion resulting in the formation of enzyme with smaller protein subunits.</strong>
J. Inherit. Metab. Dis. 6: 149-152, 1983.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6422154/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6422154</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6422154" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF02310869" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="37" class="mim-anchor"></a>
<a id="Hopkins1969" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Hopkins, I. J., Connelly, J. F., Dawson, A. G., Hird, F. J., Maddison, T. G.
<strong>Hyperammonaemia due to ornithine transcarbamylase deficiency.</strong>
Arch. Dis. Child. 44: 143-148, 1969.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/21032452/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">21032452</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21032452" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="38" class="mim-anchor"></a>
<a id="Iijima2022" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Iijima, H., Kubota, M.
<strong>A simple screening method for heterozygous female patients with ornithine transcarbamylase deficiency.</strong>
Molec. Genet. Metab. 137: 301-307, 2022.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/36252454/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">36252454</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=36252454" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="39" class="mim-anchor"></a>
<a id="Jang2018" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Jang, Y. J., LaBella, A. L., Feeney, T. P., Braverman, N., Tuchman, M., Morizono, H., Ah Mew, N., Caldovic, L.
<strong>Disease-causing mutations in the promoter and enhancer of the ornithine transcarbamylase gene.</strong>
Hum. Mutat. 39: 527-536, 2018.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29282796/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29282796</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=29282796[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29282796" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="40" class="mim-anchor"></a>
<a id="Kay1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kay, J. D. S., Hilton-Jones, D., Hyman, N.
<strong>Valproate toxicity and ornithine carbamoyltransferase deficiency. (Letter)</strong>
Lancet 328: 1283-1284, 1986. Note: Originally Volume II.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2878165/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2878165</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2878165" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="41" class="mim-anchor"></a>
<a id="Kline1981" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kline, J. J., Hug, G., Schubert, W. K., Berry, H.
<strong>Arginine deficiency syndrome: its occurrence in carbamyl phosphate synthetase deficiency.</strong>
Am. J. Dis. Child. 135: 437-442, 1981.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7234771/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7234771</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7234771" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="42" class="mim-anchor"></a>
<a id="Kodama1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kodama, H., Ohtake, A., Mori, M., Okabe, I., Tatibana, M., Kamoshita, S.
<strong>Ornithine transcarbamylase deficiency: a case with a truncated enzyme precursor and a case with undetectable mRNA activity.</strong>
J. Inherit. Metab. Dis. 9: 175-185, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3091923/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3091923</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3091923" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF01799456" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="43" class="mim-anchor"></a>
<a id="Kornfeld1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kornfeld, M., Woodfin, B. M., Papile, L., Davis, L. E., Bernard, L. R.
<strong>Neuropathology of ornithine carbamyl transferase deficiency.</strong>
Acta Neuropath. 65: 261-264, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3976361/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3976361</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3976361" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="44" class="mim-anchor"></a>
<a id="Korson1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Korson, M. S., Lillehei, C. W., Vacanti, J. P., Levy, H. L.
<strong>Liver transplantation for ornithine transcarbamylase deficiency (OTCD). (Abstract)</strong>
Am. J. Hum. Genet. 45 (suppl.): A8, 1989.
</p>
</div>
</li>
<li>
<a id="45" class="mim-anchor"></a>
<a id="Krieger1979" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Krieger, I., Snodgrass, P. J., Roskamp, J.
<strong>Atypical clinical course of ornithine transcarbamylase deficiency due to a new mutant (comparison with Reye's disease).</strong>
J. Clin. Endocr. Metab. 48: 388-392, 1979.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/429491/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">429491</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=429491" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="46" class="mim-anchor"></a>
<a id="Lee2002" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lee, J.-Y., Chang, S.-E., Suh, C.-W., Choi, J.-H., Sung, K.-J., Moon, K.-C., Koh, J.-K.
<strong>A case of acrodermatitis enteropathica-like dermatosis caused by ornithine transcarbamylase deficiency.</strong>
J. Am. Acad. Derm. 46: 965-967, 2002.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12063505/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12063505</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12063505" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="47" class="mim-anchor"></a>
<a id="Levin1969" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Levin, B., Abraham, J. M., Oberholzer, V. G., Burgess, E. A.
<strong>Hyperammonaemia: a deficiency of liver ornithine transcarbamylase. Occurrence in mother and child.</strong>
Arch. Dis. Child. 44: 152-161, 1969.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5779426/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5779426</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5779426" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/adc.44.234.152" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="48" class="mim-anchor"></a>
<a id="Lien2007" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lien, J., Nyhan, W. L., Barshop, B. A.
<strong>Fatal initial adult-onset presentation of urea cycle defect.</strong>
Arch. Neurol. 64: 1777-1779, 2007.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18071043/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18071043</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18071043" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1001/archneur.64.12.1777" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="49" class="mim-anchor"></a>
<a id="Lo2023" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lo, R. S., Cromie, G. A., Tang, M., Teng, K., Owens, K., Sirr, A., Kutz, J. N., Morizono, H., Caldovic, L., Ah Mew, N., Gropman, A., Dudley, A. M.
<strong>The functional impact of 1,570 individual amino acid substitutions in human OTC.</strong>
Am. J. Hum. Genet. 110: 863-879, 2023.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/37146589/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">37146589</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=37146589" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="50" class="mim-anchor"></a>
<a id="Lopes-Marques2021" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lopes-Marques, M., Pacheco, A. R., Peixoto, M. J., Cardoso, A. R., Serrano, C., Amorim, A., Prata, M. J., Cooper, D. N., Azevedo, L.
<strong>Common polymorphic OTC variants can act as genetic modifiers of enzymatic activity.</strong>
Hum. Mutat. 42: 978-989, 2021.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34015158/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34015158</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=34015158[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34015158" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/humu.24221" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="51" class="mim-anchor"></a>
<a id="Maddalena1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Maddalena, A., Sosnoski, D. M., Berry, G. T., Nussbaum, R. L.
<strong>Mosaicism for an intragenic deletion in a boy with mild ornithine transcarbamylase deficiency.</strong>
New Eng. J. Med. 319: 999-1003, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2843770/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2843770</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2843770" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM198810133191507" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="52" class="mim-anchor"></a>
<a id="Maddalena1988" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Maddalena, A., Spence, J. E., O'Brien, W. E., Nussbaum, R. L.
<strong>Characterization of point mutations in the same arginine codon in three unrelated patients with ornithine transcarbamylase deficiency.</strong>
J. Clin. Invest. 82: 1353-1358, 1988.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3170748/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3170748</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3170748" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1172/JCI113738" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="53" class="mim-anchor"></a>
<a id="Maestri1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Maestri, N. E., Brusilow, S. W., Clissold, D. B., Bassett, S. S.
<strong>Long-term treatment of girls with ornithine transcarbamylase deficiency.</strong>
New Eng. J. Med. 335: 855-859, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8778603/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8778603</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8778603" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM199609193351204" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="54" class="mim-anchor"></a>
<a id="Maestri1991" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Maestri, N. E., Hauser, E. R., Bartholomew, D., Brusilow, S. W.
<strong>Prospective treatment of urea cycle disorders.</strong>
J. Pediat. 119: 923-928, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1720458/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1720458</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1720458" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0022-3476(05)83044-6" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="55" class="mim-anchor"></a>
<a id="Matsuda1971" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Matsuda, I., Arashima, S., Nambu, H., Takekoshi, Y., Anakura, M.
<strong>Hyperammonemia due to a mutant enzyme of ornithine transcarbamylase.</strong>
Pediatrics 48: 595-600, 1971.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5114747/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5114747</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5114747" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="56" class="mim-anchor"></a>
<a id="Matsuda1991" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Matsuda, I., Nagata, N., Matsuura, T., Oyanagi, K., Tada, K., Narisawa, K., Kitagawa, T., Sakiyama, T., Yamashita, F., Yoshino, M.
<strong>Retrospective survey of urea cycle disorders: Part 1. Clinical and laboratory observations of thirty-two Japanese male patients with ornithine transcarbamylase deficiency.</strong>
Am. J. Med. Genet. 38: 85-89, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2012137/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2012137</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2012137" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320380119" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="57" class="mim-anchor"></a>
<a id="McCullough2000" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
McCullough, B. A., Yudkoff, M., Batshaw, M. L., Wilson, J. M., Raper, S. E., Tuchman, M.
<strong>Genotype spectrum of ornithine transcarbamylase deficiency: correlation with the clinical and biochemical phenotype.</strong>
Am. J. Med. Genet. 93: 313-319, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10946359/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10946359</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10946359" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/1096-8628(20000814)93:4&lt;313::aid-ajmg11&gt;3.0.co;2-m" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="58" class="mim-anchor"></a>
<a id="Michels1982" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Michels, V. V., Potts, E., Walser, M., Beaudet, A. L.
<strong>Ornithine transcarbamylase deficiency: long-term survival.</strong>
Clin. Genet. 22: 211-214, 1982.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7151305/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7151305</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7151305" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1399-0004.1982.tb01435.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="59" class="mim-anchor"></a>
<a id="Morsy1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Morsy, M. A., Zhao, J. Z., Ngo, T. T., Warman, A. W., O'Brien, W. E., Graham, F. L., Caskey, C. T.
<strong>Patient selection may affect gene therapy success: dominant negative effects observed for ornithine transcarbamylase in mouse and human hepatocytes.</strong>
J. Clin. Invest. 97: 826-832, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8609240/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8609240</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8609240" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1172/JCI118482" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="60" class="mim-anchor"></a>
<a id="Nagata1991" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Nagata, N., Matsuda, I., Oyanagi, K.
<strong>Estimated frequency of urea cycle enzymopathies in Japan. (Letter)</strong>
Am. J. Med. Genet. 39: 228-229, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2063931/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2063931</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2063931" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.1320390226" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="61" class="mim-anchor"></a>
<a id="Nussbaum1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Nussbaum, R. L., Boggs, B. A., Beaudet, A. L., Doyle, S., Potter, J. L., O'Brien, W. E.
<strong>New mutation and prenatal diagnosis in ornithine transcarbamylase deficiency.</strong>
Am. J. Hum. Genet. 38: 149-158, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3004207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3004207</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3004207" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="62" class="mim-anchor"></a>
<a id="Ohtake1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Ohtake, A., Takayanagi, M., Yamamoto, S., Kakinuma, H., Nakajima, H., Tatibana, M., Mori, M.
<strong>Molecular basis of ornithine transcarbamylase deficiency in spf and spf-ash mutant mice.</strong>
J. Inherit. Metab. Dis. 9: 289-291, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3099076/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3099076</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3099076" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF01799667" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="63" class="mim-anchor"></a>
<a id="Oizumi1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Oizumi, J., Ng, W. G., Koch, R., Shaw, K. N. F., Sweetman, L., Velazquez, A., Donnell, G. N.
<strong>Partial ornithine transcarbamylase deficiency associated with recurrent hyperammonemia, lethargy and depressed sensorium.</strong>
Clin. Genet. 25: 538-542, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6733950/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6733950</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6733950" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1399-0004.1984.tb00498.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="64" class="mim-anchor"></a>
<a id="Old1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Old, J. M., Briand, P. L., Purvis-Smith, S., Howard, N. J., Wilcken, B., Hammond, J., Pearson, P., Cathelineau, L., Williamson, R., Davies, K. E.
<strong>Prenatal exclusion of ornithine transcarbamylase deficiency by direct gene analysis.</strong>
Lancet 325: 73-75, 1985. Note: Originally Volume I.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2857026/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2857026</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2857026" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="65" class="mim-anchor"></a>
<a id="Pelet1990" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Pelet, A., Rotig, A., Bonaiti-Pellie, C., Rabier, D., Cormier, V., Toumas, E., Hentzen, D., Saudubray, J.-M., Munnich, A.
<strong>Carrier detection in a partially dominant X-linked disease: ornithine transcarbamylase deficiency.</strong>
Hum. Genet. 84: 167-171, 1990.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2298453/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2298453</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2298453" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF00208934" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="66" class="mim-anchor"></a>
<a id="Pembrey1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Pembrey, M. E., Old, J. M., Leonard, J. V., Rodeck, C. H., Warren, R., Davies, K. E.
<strong>Prenatal diagnosis of ornithine carbamoyl transferase deficiency using a gene specific probe.</strong>
J. Med. Genet. 22: 462-465, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3001312/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3001312</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3001312" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="67" class="mim-anchor"></a>
<a id="Qureshi1979" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Qureshi, I. A., Letarte, J., Ouellet, R.
<strong>Ornithine transcarbamylase deficiency in mutant mice. I. Studies on the characterization of enzyme defect and suitability as animal model of human disease.</strong>
Pediat. Res. 13: 807-811, 1979.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/481951/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">481951</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=481951" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="68" class="mim-anchor"></a>
<a id="Ricciuti1976" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Ricciuti, F. C., Gelehrter, T. D., Rosenberg, L. E.
<strong>X-chromosome inactivation in human liver: confirmation of X-linkage of ornithine transcarbamylase.</strong>
Am. J. Hum. Genet. 28: 332-338, 1976.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/941900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">941900</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=941900" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="69" class="mim-anchor"></a>
<a id="Rodeck1982" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Rodeck, C. H., Patrick, A. D., Pembrey, M. E., Tzannatos, C., Whitfield, A. E.
<strong>Fetal liver biopsy for prenatal diagnosis of ornithine carbamyl transferase deficiency.</strong>
Lancet 320: 297-300, 1982. Note: Originally Volume II.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6124717/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6124717</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6124717" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="70" class="mim-anchor"></a>
<a id="Rosenberg1983" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Rosenberg, L. E., Kalousek, F., Orsulak, M. D.
<strong>Biogenesis of ornithine transcarbamylase in spf(ash) mutant mice: two cytoplasmic precursors, one mitochondrial enzyme.</strong>
Science 222: 426-428, 1983.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6623083/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6623083</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6623083" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1126/science.6623083" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="71" class="mim-anchor"></a>
<a id="Rowe1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Rowe, P. C., Newman, S. L., Brusilow, S. W.
<strong>Natural history of symptomatic partial ornithine transcarbamylase deficiency.</strong>
New Eng. J. Med. 314: 541-547, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3945292/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3945292</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3945292" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="72" class="mim-anchor"></a>
<a id="Rozen1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Rozen, R., Fox, J., Fenton, W. A., Horwich, A. L., Rosenberg, L. E.
<strong>Gene deletion and restriction fragment length polymorphisms at the human ornithine transcarbamylase locus.</strong>
Nature 313: 815-817, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2983225/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2983225</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2983225" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/313815a0" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="73" class="mim-anchor"></a>
<a id="Russell1962" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Russell, A., Levin, B., Oberholzer, V. G., Sinclair, L.
<strong>Hyperammonaemia. A new instance of an inborn enzymatic defect of the biosynthesis of urea.</strong>
Lancet 280: 699-700, 1962. Note: Originally Volume II.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/13975632/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">13975632</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=13975632" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0140-6736(62)90508-1" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="74" class="mim-anchor"></a>
<a id="Schwartz1986" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Schwartz, M., Christensen, E., Christensen, N. C., Skovby, F., Davies, K. E., Old, J. M.
<strong>Detection and exclusion of carriers of ornithine transcarbamylase deficiency by RFLP analysis.</strong>
Clin. Genet. 29: 449-452, 1986.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3017613/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3017613</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3017613" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1399-0004.1986.tb00520.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="75" class="mim-anchor"></a>
<a id="Scott1972" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Scott, C. R., Chiang-Teng, C., Goodman, S. I., Greensher, A., Mace, J. W.
<strong>X-linked transmission of ornithine-transcarbamylase deficiency. (Letter)</strong>
Lancet 300: 1148 only, 1972. Note: Originally Volume II.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4117228/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4117228</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4117228" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0140-6736(72)92756-0" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="76" class="mim-anchor"></a>
<a id="Shapiro1980" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Shapiro, J. M., Schaffner, F., Tallan, H. H., Gaull, G. E.
<strong>Mitochondrial abnormalities of liver in primary ornithine transcarbamylase deficiency.</strong>
Pediat. Res. 14: 735-759, 1980.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7383749/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7383749</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7383749" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1203/00006450-198005000-00006" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="77" class="mim-anchor"></a>
<a id="Shih1978" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Shih, V. E., Berson, E. L., Mandell, R., Schmidt, S. Y.
<strong>Ornithine ketoacid transaminase deficiency in gyrate atrophy of the choroid and retina.</strong>
Am. J. Hum. Genet. 30: 174-179, 1978.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/655164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">655164</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=655164" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="78" class="mim-anchor"></a>
<a id="Short1973" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Short, E. M., Conn, H. O., Snodgrass, P. J., Campbell, A. G. M., Rosenberg, L. E.
<strong>Evidence for X-linked dominant inheritance of ornithine transcarbamylase deficiency.</strong>
New Eng. J. Med. 288: 7-12, 1973.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4681915/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4681915</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4681915" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM197301042880102" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="79" class="mim-anchor"></a>
<a id="Snodgrass1978" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Snodgrass, P. J., Wappner, R. S., Brandt, I. K.
<strong>White cell ornithine transcarbamylase activity cannot detect the liver enzyme deficiency. (Letter)</strong>
Pediat. Res. 12: 873, 1978.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/683745/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">683745</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=683745" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="80" class="mim-anchor"></a>
<a id="Stoll1978" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Stoll, C., Bieth, R., Dreyfus, J., Flori, E., Lutz, P., Levy, J.-M.
<strong>Une nouvelle famille avec mutation du gene de structure de l'ornithine carbamyltransferase humaine.</strong>
Arch. Franc. Pediat. 35: 512-518, 1978.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/678030/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">678030</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=678030" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="81" class="mim-anchor"></a>
<a id="Sunshine1972" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Sunshine, P., Lindenbaum, J. E., Levy, H. L., Freeman, J. M.
<strong>Hyperammonemia due to a defect in hepatic ornithine transcarbamylase.</strong>
Pediatrics 50: 100-111, 1972.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5038084/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5038084</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5038084" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
</li>
<li>
<a id="82" class="mim-anchor"></a>
<a id="Testai2010" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Testai, F. D., Gorelick, P. B.
<strong>Inherited metabolic disorders and stroke part 2: homocystinuria, organic acidurias, and urea cycle disorders.</strong>
Arch. Neurol. 67: 148-153, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20142522/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20142522</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20142522" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="83" class="mim-anchor"></a>
<a id="Thaler1974" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Thaler, M. M., Hoogenraad, N. J., Boswell, M.
<strong>Reye's syndrome due to a novel protein-tolerant variant of ornithine-transcarbamylase deficiency.</strong>
Lancet 304: 438-440, 1974. Note: Originally Volume II.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4137171/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4137171</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4137171" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="84" class="mim-anchor"></a>
<a id="Torkzaban2019" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Torkzaban, M., Haddad, A., Baxter, J. K., Berghella, V., Gahl, W. A., Al-Kouatly, H.
<strong>Maternal ornithine transcarbamylase deficiency, a genetic condition associated with high maternal and neonatal mortality every clinician should know: a systematic review.</strong>
Am. J. Med. Genet. 179A: 2091-2100, 2019.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31441224/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31441224</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31441224" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="85" class="mim-anchor"></a>
<a id="Tripp1981" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Tripp, J. H., Hargreaves, T., Anthony, P. P., Searle, J. F., Miller, P., Leonard, J. V., Patrick, A. D., Oberholzer, V. G.
<strong>Sodium valproate and ornithine carbamyl transferase deficiency. (Letter)</strong>
Lancet 317: 1165-1166, 1981. Note: Originally Volume I.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6112522/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6112522</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6112522" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="86" class="mim-anchor"></a>
<a id="Tuchman1996" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Tuchman, M., Plante, R. J., Garcia-Perez, M. A., Rubio, V.
<strong>Relative frequency of mutations causing ornithine transcarbamylase deficiency in 78 families.</strong>
Hum. Genet. 97: 274-276, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8786061/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8786061</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8786061" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="87" class="mim-anchor"></a>
<a id="Tuchman1993" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Tuchman, M.
<strong>Mutations and polymorphisms in the human ornithine transcarbamylase gene.</strong>
Hum. Mutat. 2: 174-178, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8364586/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8364586</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8364586" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="88" class="mim-anchor"></a>
<a id="Veres1987" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Veres, G., Gibbs, R. A., Scherer, S. E., Caskey, C. T.
<strong>The molecular basis of the sparse fur mouse mutation.</strong>
Science 237: 415-417, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3603027/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3603027</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3603027" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="89" class="mim-anchor"></a>
<a id="Wareham1987" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wareham, K. A., Lyon, M. F., Glenister, P. H., Williams, E. D.
<strong>Age related reactivation of an X-linked gene.</strong>
Nature 327: 725-727, 1987.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3600770/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3600770</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3600770" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/327725a0" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="90" class="mim-anchor"></a>
<a id="Wettke-Schafer1983" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wettke-Schafer, R., Kantner, G.
<strong>X-linked dominant inherited diseases with lethality in hemizygous males.</strong>
Hum. Genet. 64: 1-23, 1983.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6873941/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6873941</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6873941" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="91" class="mim-anchor"></a>
<a id="Wilnai2018" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wilnai, Y., Blumenfeld, Y. J., Cusmano, K., Hintz, S. R., Alcorn, D., Benitz, W. E., Berquist, W. E., Bernstein, J. A., Castillo, R. O., Concepcion, W., Cowan, T. M., Cox, K. L., and 10 others.
<strong>Prenatal treatment of ornithine transcarbamylase deficiency.</strong>
Molec. Genet. Metab. 123: 297-300, 2018.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29396029/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29396029</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29396029" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="92" class="mim-anchor"></a>
<a id="Wilson2001" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Wilson, C. J., Lee, P. J., Leonard, J. V.
<strong>Plasma glutamine and ammonia concentrations in ornithine carbamoyltransferase deficiency and citrullinaemia.</strong>
J. Inherit. Metab. Dis. 24: 691-695, 2001.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11804205/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11804205</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11804205" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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</p>
</div>
</li>
<li>
<a id="93" class="mim-anchor"></a>
<a id="Yorifuji1998" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Yorifuji, T., Muroi, J., Uematsu, A., Tanaka, K., Kiwaki, K., Endo, F., Matsuda, I., Nagasaka, H., Furusho, K.
<strong>X-inactivation pattern in the liver of a manifesting female with ornithine transcarbamylase (OTC) deficiency.</strong>
Clin. Genet. 54: 349-353, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9831349/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9831349</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9831349" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1034/j.1399-0004.1998.5440415.x" target="_blank">Full Text</a>]
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Yudkoff, M., Daikhin, Y., Nissim, I., Jawad, A., Wilson, J., Batshaw, M.
<strong>In vivo nitrogen metabolism in ornithine transcarbamylase deficiency.</strong>
J. Clin. Invest. 98: 2167-2173, 1996.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8903337/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8903337</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8903337" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1172/JCI119023" target="_blank">Full Text</a>]
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<a id="Yudkoff1980" class="mim-anchor"></a>
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Yudkoff, M., Yang, W., Snodgrass, P. J., Segal, S.
<strong>Ornithine transcarbamylase deficiency in a boy with normal development.</strong>
J. Pediat. 96: 441-443, 1980.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7188954/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7188954</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7188954" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0022-3476(80)80694-9" target="_blank">Full Text</a>]
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Hilary J. Vernon - updated : 08/09/2023
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Hilary J. Vernon - updated : 02/21/2023<br>Hilary J. Vernon - updated : 11/16/2020<br>Hilary J. Vernon - updated : 05/19/2020<br>Ada Hamosh - updated : 1/7/2015<br>Cassandra L. Kniffin - updated : 10/11/2010<br>Cassandra L. Kniffin - updated : 3/31/2008<br>Cassandra L. Kniffin -updated : 10/10/2005<br>Cassandra L. Kniffin - reorganized : 12/4/2003<br>Gary A. Bellus - updated : 4/24/2003<br>Victor A. McKusick - updated : 2/21/2002<br>Ada Hamosh - updated : 1/30/2002<br>Ada Hamosh - updated : 1/23/2002<br>Ada Hamosh - updated : 5/16/2001<br>Ada Hamosh - updated : 4/23/2001<br>Victor A. McKusick - updated : 4/5/2001<br>Victor A. McKusick - updated : 2/23/2000<br>Sonja A. Rasmussen - updated : 10/1/1999<br>Victor A. McKusick - updated : 1/26/1999<br>Victor A. McKusick - updated : 6/18/1997<br>Victor A. McKusick - updated : 5/15/1997<br>Cynthia K. Ewing - updated : 10/8/1996
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Creation Date:
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Victor A. McKusick : 6/4/1986
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carol : 08/10/2023
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<strong>#</strong> 311250
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ORNITHINE TRANSCARBAMYLASE DEFICIENCY, HYPERAMMONEMIA DUE TO
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<em>Alternative titles; symbols</em>
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ORNITHINE CARBAMOYLTRANSFERASE DEFICIENCY<br />
OTC DEFICIENCY
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<strong>SNOMEDCT:</strong> 80908008; &nbsp;
<strong>ICD10CM:</strong> E72.4; &nbsp;
<strong>ORPHA:</strong> 664; &nbsp;
<strong>DO:</strong> 9271; &nbsp;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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Xp11.4
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Ornithine transcarbamylase deficiency
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311250
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X-linked
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3
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OTC
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300461
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because ornithine transcarbamylase deficiency is caused by mutation in the gene encoding ornithine carbamoyltransferase (OTC; 300461) on chromosome Xp11.</p>
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<strong>Description</strong>
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<p>Ornithine transcarbamylase deficiency is an X-linked inborn error of metabolism of the urea cycle, which causes hyperammonemia. The disorder is treatable with supplemental dietary arginine and low protein diet.</p><p>Urea cycle disorders are characterized by the triad of hyperammonemia, encephalopathy, and respiratory alkalosis. Five disorders involving different defects in the biosynthesis of the enzymes of the urea cycle have been described: OTC deficiency, carbamyl phosphate synthetase deficiency (237300), argininosuccinate synthetase deficiency, or citrullinemia (215700), argininosuccinate lyase deficiency (207900), and arginase deficiency (207800).</p>
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<strong>Clinical Features</strong>
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<p>Russell et al. (1962) described 2 cousins with chronic ammonia intoxication and mental deterioration. By liver biopsy, the activity of hepatic OTC was shown to be very low. A defect was presumed to be present in urea synthesis at the level of conversion of ornithine to citrulline. </p><p>Levin et al. (1969) reported an affected female infant whose mother had an aversion to protein and raised plasma ammonia levels, whereas the father was normal. In another infant, a male, Levin et al. (1969) found what they considered a variant of the usual hyperammonemia caused by OTC deficiency, presumably due to a different enzymatic change. Enzyme activity was 25% of normal, rather than 5 to 7% of normal as in other cases, and other properties of the enzyme showed differences from the normal. The clinical picture was milder than in the usual cases. Holmes et al. (1987) also described a mild variant of OTC deficiency. </p><p>Campbell et al. (1971, 1973) reported lethal neonatal hyperammonemia due to complete ornithine transcarbamylase deficiency. They suggested that mutation in the gene encoding the enzyme may lead to partial deficiency in heterozygous females and to complete deficiency in hemizygous males. </p><p>Thaler et al. (1974) described a 'novel protein tolerant variant' of OTC deficiency in a child with encephalopathy with fatty visceral degeneration suggestive of Reye syndrome. Krieger et al. (1979) reported a male infant with OTC deficiency who was relatively symptom free for 4 months, but gradually developed severe spasticity due to cerebral atrophy, and died at 13 months of age. Liver OTC activity was 1.5% of normal. The authors noted that the clinical picture of OTC deficiency during acute exacerbations with microvesicular fat accumulation in the liver may suggest Reye syndrome. </p><p>Bruton et al. (1970) described astrocyte transformation to Alzheimer type II glia, a feature of any form of hyperammonemia. Kornfeld et al. (1985) reported neuropathologic findings in 2 cases of OTC deficiency. A 3-day-old boy showed gliosis mainly in the brainstem, and a 2-year-old girl showed widespread gliosis and ulegyria of the cerebral cortex, as well as atrophy in the internal granular layer of the cerebellum. </p><p>Drogari and Leonard (1988) described 6 affected boys with relatively late onset of clinical symptoms. One of them was a boy who during childhood was considered a 'very difficult child, introverted with volcanic tempers.' At the age of 12 years, he had an episode of confusion for which he was admitted to hospital, but no cause was found. At the age of 14 years, he was admitted to hospital deeply unconscious after a high protein meal the night before admission. Urine orotic acid excretion was raised, and his mother was found to be a carrier. Thereafter, he was treated with a low protein diet, arginine supplements, and sodium benzoate. He had further episodes of hyperammonemia, however, particularly precipitated by energy restriction. At the age of 18 years he performed commendably in examinations and was accepted for medical school. Finkelstein et al. (1989, 1990) described 21 male patients who presented after age 28 days with what the authors defined as late-onset OTC deficiency. The patients appeared normal at birth, but irritability, vomiting and lethargy, which were often episodic, developed later. The age of presentation ranged from 2 months to 44 years. </p><p>Partial deficiency in the male, a presumably allelic form, was reported by Matsuda et al. (1971) and by Oizumi et al. (1984). Oizumi et al. (1984) reported the case of a 6-year-old boy who had intermittent coma with hyperammonemia precipitated by infections. Liver biopsy showed OTC activity 16% of normal. The mother showed elevated orotic acid excretion in the urine following protein load. Supplementation of dietary arginine abolished the episodes of hyperammonemia in the boy. Matsuda et al. (1991) described the clinical and laboratory features of 32 Japanese patients with OTC deficiency. They divided their patients into 3 groups, based on clinical manifestations and age of onset: group 1 (0 to 28 days), group 2 (29 days to 5 years), and group 3 (greater than 5 years). The lowest mortality and incidence of mental retardation was among the group 2 patients. Patients in groups 1 and 3 had similar mortality rates and enzyme activities. These patients had the highest citrulline levels and were asymptomatic prior to their first episode of hyperammonemia. The authors emphasized that the incidence of late-onset OTC deficiency is higher than previously recognized. </p><p>Anadiotis et al. (2001) reported a 15-year-old male patient with OTC deficiency who developed pancreatitis while taking a low protein diet, citrulline, and sodium phenylbutyrate. </p><p>Lee et al. (2002) noted that there have been several reports of acrodermatitis enteropathica-like dermatosis in association with inborn errors of the urea cycle, in citrullinemia associated with argininosuccinate synthase deficiency (Goldblum et al., 1986), and in carbamoyl phosphate synthetase deficiency (Kline et al., 1981). Lee et al. (2002) speculated that since arginine represents such a large proportion of the amino acid composition of epidermal keratins, arginine deficiency associated with urea cycle defects may contribute to compromised epidermal barrier function and skin lesions in affected infants. </p><p>Lien et al. (2007) reported a 52-year-old man who died suddenly of hyperammonemia after routine surgery for removal of a throat polyp. Eight days after surgery, he developed confusion, ataxia, and paranoia, which progressed to seizures, cerebral edema, coma, and death within 3 days. Prior medical history was unremarkable. The patient's asymptomatic 20-year-old daughter presented for prenatal evaluation, and her twin boys were both found to be carriers of a mutation in the OTC gene. The mother was heterozygous for the mutation, but DNA analysis on autopsy samples from her father were unsuccessful. Both baby boys were healthy on a low protein diet. Lien et al. (2007) emphasized the late onset and unusual presentation of OTC deficiency in the older man. </p><p>In a review of inherited metabolic disorders and stroke, Testai and Gorelick (2010) noted that patients with urea cycle defects, including CPS1 deficiency (237300), OTC deficiency, and citrullinemia (215700) rarely have strokes. </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. The most common disorder was ornithine transcarbamylase deficiency, accounting for more than half of the participants. The overall prevalence of UCDs in the population was calculated as 1 per 35,000, with two-thirds presenting initial symptoms after the neonatal period. Batshaw et al. (2014) found the mortality rate to be 24% in neonatal-onset cases and 11% in late-onset cases. The most common precipitant of clinical hyperammonemic episodes in the post-neonatal period was intercurrent infections. Elevations in both blood ammonia and glutamine appeared to be biomarkers for neurocognitive outcome. In terms of chronic treatment, low protein diet appeared to result in normal weight but decreased linear growth, while nitrogen scavenger therapy with phenylbutyrate resulted in low levels of branched chain amino acids. Batshaw et al. (2014) found an unexpectedly high risk for hepatic dysfunction in patients with ornithine transcarbamylase deficiency. </p><p><strong><em>Heterozygous Females</em></strong></p><p>
Rowe et al. (1986) reviewed 13 symptomatic female heterozygotes. They presented as early as the first week of life or as late as the sixth year. Symptoms before diagnosis were nonspecific: episodic extreme irritability (100%), episodic vomiting and lethargy (100%), protein avoidance (92%), ataxia (77%), stage II coma (46%), delayed growth (38%), developmental delay (38%), and seizures (23%). Onset at the time of weaning from breast milk was frequent. Including the proband, 42% of females in the 13 families had symptoms. </p><p>Gilchrist and Coleman (1987) reported 2 heterozygous females who had late onset of severe symptoms. Encephalopathy and focal neurologic deficits began at age 36 years in 1 and at age 38 years in the other. The second had increased urine orotate after a protein meal and had had a lifelong aversion to eating meat, which usually precipitated headaches. </p><p>Arn et al. (1989) discussed phenotypic effects of heterozygosity for mutations in the OTC gene. Arn et al. (1990) reported that otherwise normal women who are carriers of a mutant OTC allele are at increased risk for hyperammonemic coma, especially during puerperium. They recommended that any woman who presents with an episode of progressive lethargy and stupor, evidence of acute cortical dysfunction, or coma, especially during pregnancy, be examined for OTC deficiency by pedigree analysis, a search for a history of previous episodes, and the measurement of plasma ammonium and, if immediately available, plasma glutamine levels. The early identification of hyperammonemia provides an opportunity to correct plasma ammonium levels by intravenous therapy with sodium benzoate, sodium phenylacetate, and arginine hydrochloride. </p><p>Lee et al. (2002) reported a female infant with skin lesions resembling acrodermatitis enteropathica who was subsequently found to have OTC deficiency. Infectious causes and zinc deficiency were ruled out, and resolution of the eruption occurred after arginine and citrulline supplementation was instituted. </p><p>Torkzaban et al. (2019) reported pregnancy outcomes in 36 women who were heterozygous for OTC deficiency based on a review of the literature. Twenty women were known to be heterozygous prior to pregnancy; of these 20 women, 7 had neurologic or psychiatric symptoms during pregnancy or postpartum, 3 had hyperammonemia during pregnancy, and 2 had hyperammonemia and required ICU admission and dialysis postpartum. There were no maternal deaths in this group. Of the 16 women not known to be heterozygous prior to pregnancy, 13 had neurologic or psychiatric symptoms during pregnancy or postpartum, 4 had hyperemesis gravidarum, 11 had hyperammonemia and ICU admission, and 7 required dialysis. In this group, 3 had prolonged hospitalization and there were 5 maternal deaths. Torkzaban et al. (2019) concluded that maternal heterozygous status of OTC deficiency is associated with higher maternal morbidity and mortality when it is diagnosed during pregnancy compared to when it is diagnosed prior to pregnancy. </p><p><strong><em>Valproate Sensitivity</em></strong></p><p>
In males with OTC deficiency, sodium valproate may precipitate acute liver failure (Tripp et al., 1981). Hjelm et al. (1986) concluded that the vulnerability of toxic effects of valproate extends to heterozygotes as well. They described a family in which 2 daughters and a son died in childhood, all with clinical features suggesting a metabolic disorder; in one, valproate seemed to have accelerated death. They concluded that the mother was a heterozygote for OTC deficiency. Valproate sensitivity in OTC deficiency is comparable to vincristine neuropathy in Charcot-Marie-Tooth disease (118200). </p><p>Honeycutt et al. (1992) reported a previously undiagnosed heterozygous woman who had symptomatic hyperammonemia during initiation of valproate therapy. Kay et al. (1986) had reported a similar patient. Valproate inhibits ureagenesis and can be toxic to mitochondria. </p>
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<strong>Inheritance</strong>
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<p>Scott et al. (1972) presented 2 kindreds that supported X-linked recessive inheritance of OTC deficiency. Short et al. (1973) studied 4 families, all consistent with X-linked inheritance. In the liver of a woman heterozygous for OTC deficiency, Ricciuti et al. (1976) demonstrated 2 classes of cells, one deficient and one normal in enzyme activity. The findings of cellular mosaicism confirmed that the gene for OTC is X-linked. Thus, the evidence of X-linked dominant inheritance is based on (1) the severe nature of the disorder in males with almost complete absence of enzyme in most cases; (2) wide variation in clinical severity and in enzyme level in heterozygous women; (3) demonstration of the Lyon phenomenon in the liver of heterozygous females; and (4) demonstration of X-linkage in the mouse (see DeMars et al., 1976). </p>
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<strong>Mapping</strong>
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<p>Burdakin and Norum (1981) observed at least 1 recombinant in 3 opportunities for the linkage of OTC deficiency and G6PD (305900) on the X chromosome. The loci were later found to be at opposite ends of the X chromosome.</p>
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<strong>Diagnosis</strong>
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</div>
<span class="mim-text-font">
<p>Rowe et al. (1986) suggested that family history, dietary history, episodic nonspecific symptoms, response to withdrawal of protein, and other characteristics should permit early diagnosis. In 5 patients tested, IQ was below 70 at the time of diagnosis. </p><p>OTC is expressed in the liver and in the mucosa of the small intestine. Hamano et al. (1988) described the identification of a carrier of OTC deficiency by means of immunocytochemical examination of a biopsy specimen from the duodenal mucosa. OTC-negative cells were distributed around 1 side of some villi, whereas OTC-positive cells were located on the other side. The epithelial cells of the intestine arise from the division of the crypt cells and then move up along the sides of the villi. The epithelium of individual crypts is thought to be composed of cells of a single parental type. </p><p>About 15% of heterozygous females have life-threatening hyperammonemic comas. Both symptomatic and asymptomatic carriers show increased orotic acid excretion, especially under protein loading tests. Pelet et al. (1990) found that the test is rarely negative in obligate carriers, perhaps no more often than in 8% of carriers. </p><p>Hauser et al. (1990) described a test that can be substituted for nitrogen loading for identification of heterozygous females. In the nitrogen loading test, there is intramitochondrial accumulation of carbamoyl phosphate. The excess carbamoyl phosphate is diffused into the cytosol where it functions as a substrate to enhance the biosynthesis of pyrimidine, resulting in the accumulation and excretion of orotic acid. In the test proposed by Hauser et al. (1990), a single oral dose of allopurinol substitutes for the nitrogen load. The effectiveness of the method depends on the inhibitory effect of oxypurinol ribonucleotide (a metabolite of allopurinol) on orotidine monophosphate decarboxylase, which leads to the accumulation of orotidine monophosphate and its precursor orotic acid, and ultimately to orotic aciduria and orotidinuria. </p><p>Grompe et al. (1991) offered a diagnostic algorithm for OTC deficiency. Although the accuracy of prenatal and carrier detection of OTC deficiency has been greatly improved by linkage analysis since the cloning of the gene, RFLP-based diagnosis is limited in this disorder in which many of the cases represent new mutations. </p><p>Yudkoff et al. (1996) developed a new technique that monitors metabolic competence in female heterozygotes for OTC deficiency. They concluded that the test effectively monitors in vivo nitrogen metabolism and may obviate the need for liver biopsy to measure enzyme activity in OTC deficiency. Asymptomatic OTC deficiency carriers form urea at a normal rate, indicating that ureagenesis can be competent even though enzyme activity is below normal. Although ostensibly asymptomatic OTC deficiency carriers form urea at a normal rate, their nitrogen metabolism is still abnormal, as reflected in their increased production of 5-(15)N-glutamine. The new test may be important for monitoring the efficacy of novel treatments for OTC deficiency, e.g., liver transplantation and gene therapy. The method uses mass spectrometry to measure conversion of (15)NH(4)Cl to (15)N-urea and 5-(15)N-glutamine following an oral load of (15)NH(4)Cl. </p><p>Bowling et al. (1999) reported a family with 2 consecutive males with OTC deficiency caused by mutation in the OTC gene. The mother had normal biochemical studies. Genotyping of the mother was performed on peripheral blood leukocytes and skin fibroblasts and showed no mutation, strongly suggesting gonadal mosaicism. The authors noted that gonadal mosaicism needs to be considered when counseling couples in which the mother has had a previously affected child with OTC deficiency but does not appear to be a carrier. </p><p>Iijima and Kubota (2022) demonstrated that the metabolite ratio (glutamine+glycine)/(citrulline+arginine) had a 100% sensitivity and 98% specificity in discriminating 10 female patients with OTC deficiency from 966 patients with other disorders, including cardiac, neurologic, liver, intestinal, and renal diseases. Furthermore, this ratio was significantly higher in females with OTC deficiency when they were acutely ill compared to when they were asymptomatic. </p><p><strong><em>Prenatal Diagnosis</em></strong></p><p>
In a report of prenatal diagnosis of OTC deficiency, Pembrey et al. (1985) suggested that regardless of the predicted outcome as far as the fetus is concerned, the biochemical status of the carrier mother should be monitored because hyperammonemia and arginine deficiency might have a deleterious effect on the fetus, perhaps particularly if a female fetus is heterozygous for the OTC deficiency gene. </p><p>Fox et al. (1986, 1986) discussed the use of DNA polymorphisms in the prenatal diagnosis of OTC deficiency. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Clinical Management</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Batshaw et al. (1982) reported on therapy of 26 patients with inborn errors of urea synthesis by activation of alternative pathways of waste nitrogen synthesis and excretion. In 7 with deficiency of argininosuccinate synthetase (citrullinemia) and 10 with deficiency of argininosuccinate lyase (argininosuccinic aciduria), excretion of citrulline and argininosuccinate served as waste nitrogen products because they contain nitrogen normally destined for urea synthesis; synthesis and excretion of these substances was enhanced by arginine supplementation. Administration of sodium benzoate further diverted ammonium nitrogen from the defective urea pathway to hippurate synthesis by way of the glycine cleavage complex in the above 2 disorders, as well as in ornithine transcarbamylase deficiency and hyperammonemia due to carbamoyl phosphate synthetase deficiency. </p><p>Brusilow et al. (1984) reported the successful treatment of episodic hyperammonemia in children with carbamoyl phosphate synthetase deficiency, ornithine transcarbamylase deficiency, and citrullinemia. Treatment made use of intravenous sodium benzoate, sodium phenylacetate and arginine, nitrogen-free intravenous alimentation, and, when other measures failed, dialysis. </p><p>Michels et al. (1982) reported survival to over 4 years of age in a male with OTC deficiency who was treated with a very low protein diet supplemented with essential amino acids and keto acid analog of essential amino acids. Korson et al. (1989) described the successful use of liver transplantation in the treatment of OTC deficiency. </p><p>Maestri et al. (1991) described a diagnostic and therapeutic protocol designed to prevent clinical expression of inborn errors of urea synthesis in the neonatal period. In 7 of 32 affected infants with carbamoyl phosphate synthetase deficiency, argininosuccinate synthetase deficiency, and argininosuccinate lyase deficiency, therapy was effective in avoiding neonatal hyperammonemic coma and death. When treated prospectively, 5 of 8 patients with OTC deficiency avoided severe hyperammonemia and survived the neonatal period. Two of the patients with OTC deficiency subsequently died; 3 others had received orthotopic liver transplants. The experience with all of the surviving patients suggested a more favorable neurologic outcome than that achieved in patients rescued from neonatal hyperammonemic coma. Maestri et al. (1996) reported on the long-term outcome of 32 girls with OTC deficiency enrolled in a treatment protocol who had at least 1 episode of encephalopathy. The authors reported a survival rate greater than 90% at 5 years of age. The frequency of hyperammonemic episodes decreased with increasing age and with sodium phenylacetate or sodium phenylbutyrate treatment. Although mean IQ before treatment was in the low average range, 19 of the 23 girls in whom intelligence was tested longitudinally had stable test scores. </p><p>Wilson et al. (2001) reviewed the plasma ammonia and glutamine concentrations during long-term management of 7 patients with OTC deficiency and 3 patients with citrullinemia. Patients with citrullinemia tended to have higher plasma ammonia concentrations for a given plasma glutamine concentration compared to those with OTC deficiency, and there was not a simple linear relationship between glutamine and ammonia in either condition. </p><p>Wilnai et al. (2018) reported perinatal treatment in 2 OTC deficiency carrier mothers with male fetuses who had prenatal diagnoses of OTC. At the start of labor, the mothers were each given a bolus of Ammonul at a dose of 5.5 gm per meter squared body surface area and arginine at a dose of 4 gm per meter squared body surface area, followed by maintenance Ammonul and arginine until delivery. Intravenous dextrose was also given. Wilnai et al. (2018) found that the ammonia, glutamine, and alanine levels were normal in the newborns at birth. The infants were started on intravenous maintenance Ammonul, arginine, dextrose, and electrolytes in the intensive care unit and transitioned to oral sodium phenylbutyrate and citrulline before discharge. Orthotopic liver transplant occurred at age 3 months in one infant and at age 5 months in the other. Development was described as normal in both patients at 7 years and 3 years, respectively. </p><p>Torkzaban et al. (2019) discussed recommendations for metabolic management of women with OTC deficiency during and after labor and delivery. They recommended delivery at 39 weeks' gestation to ensure management by a maternal fetal medicine specialist, metabolic dietitian, geneticist, and neonatologist. During labor and delivery, IV fluids with dextrose should be provided to prevent catabolism. Ammonia should be measured every 6 hours during labor and delivery and then for at least 72 hours after. Patients should be given discharge instructions describing the symptoms of hyperammonemia in the postpartum period and to report any of these symptoms to their doctor. Torkzaban et al. (2019) also recommended that a dietitian be consulted in the postpartum period with the goal of avoiding both catabolism and protein overload. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Molecular Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Rozen et al. (1985) gave the first reported example of an OTC gene deletion that could be identified cytogenetically in a patient with OTC deficiency. In a boy with a mild form of OTC deficiency, Maddalena et al. (1988) found somatic mosaicism for an intragenic deletion of the OTC gene (300461.0001). In 3 of 24 unrelated patients with OTC deficiency, Maddalena et al. (1988) identified 2 different point mutations in the same codon of the OTC gene (300461.0002-300461.0003). The patients included 2 males with severe neonatal onset and a female patient with mild disease. In 5 unrelated patients with OTC deficiency, Grompe et al. (1989) identified 4 mutations and a polymorphism in the OTC gene (300461.0004-300461.0009). </p><p>In a catalog of mutations in the OTC gene, Tuchman (1993) reported that approximately 10 to 15% of all molecular alterations associated with OTC deficiency were large deletions involving all or part of the OTC gene. Tuchman et al. (1996) estimated that approximately 90 different mutations associated with OTC deficiency had been defined. </p><p>Jang et al. (2018) identified promoter or enhancer mutations of the OTC gene in 9 patients with a clinical diagnosis of OTC deficiency but without identifiable mutations in the exons and exon/intron boundaries of the OTC gene. Six mutations in the OTC promoter (c.-106C-A, c.-115C-T, c.-116C-T, c.-106C-A, c.-115C-T, c.-116C-T) were identified in patients 1-8, and 1 mutation in an OTC enhancer (c.-9384G-T) was identified in patient 9. Using a dual luciferase assay to establish effects on gene expression, the authors found that each of the promoter mutations as well as the enhancer mutation resulted in reduction of luciferase activity. </p><p>Lopes-Marques et al. (2021) evaluated the role of 2 polymorphisms in the OTC gene, K46R and Q270R, on the function of wildtype OTC and OTC with the known pathogenic mutation R40H (300461.0029) in HEK293 cells. The combination of both polymorphisms resulted in a significant increase in OTC enzyme function, whereas only the Q270R polymorphism resulted in a significant increase in OTC enzyme activity in cis with the R40H mutation. Structural analysis suggested that the Q270R polymorphism stabilized OTC with the R40H mutation. </p><p>Lo et al. (2023) developed a yeast growth-based assay to evaluate the function of OTC with each of 1,570 amino acid substitutions, which represented 84% of the missense mutations that were potentially caused by single nucleotide substitutions in the OTC gene. Residual growth values were used to categorize the mutations into functionally unimpaired (greater than 90% residual growth), functionally hypomorphic (5-90% residual growth), or functionally amorphic (less than 5% residual growth). Correlations were identified between the residual growth values and disease severity, relative conservation, and functional gene regions. The exception to this was the 13-amino acid SMG loop of OTC, which appeared to be functionally relevant in human cells but not in yeast cells. </p><p><strong><em>X Inactivation</em></strong></p><p>
To understand the correlation between X-inactivation status and the clinical phenotype of carrier females (which can vary from asymptomatic to severe hyperammonemia), Yorifuji et al. (1998) analyzed the X-inactivation pattern of peripheral blood leukocytes in a family consisting of a clinically normal mother and 2 daughters with a severe manifestation. In addition, they obtained tissue samples from various parts of the liver of one of the daughters and analyzed X-inactivation patterns and residual OTC activities. The X inactivation of peripheral blood leukocytes was nearly random in these carrier females and showed no correlation with the disease phenotype; however, the X inactivation of the liver was much more skewed and correlated well with the OTC activity of all samples. The degree of X inactivation varied considerably, even within the same liver. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Genotype/Phenotype Correlations</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>McCullough et al. (2000) examined the genotype/phenotype correlations of 157 probands with OTC deficiency, including 57 heterozygous females. In patients with mutations that abolished enzyme activity, the severe clinical and biochemical phenotype was homogeneous. The males in this group presented within the first few days of life with high mortality and morbidity. Most patients with the late-onset form had missense mutations in the OTC gene, although a few had 3-bp deletions, and late-onset patients had residual enzyme activity ranging from 26 to 74% of normal control values. Mutations in manifesting females were primarily of the neonatal-onset type. Substitutions occurring in CpG dinucleotides accounted for approximately 31% of all mutations. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Population Genetics</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Nagata et al. (1991) estimated that OTC deficiency has a frequency of 1 in 80,000 births in Japan. The total frequency of this and the other urea cycle enzymopathies, carbamoyl phosphate synthetase deficiency, argininosuccinate synthetase deficiency, argininosuccinate lyase deficiency, and arginase deficiency, in Japan was 1 in 46,000. </p><p>Testai and Gorelick (2010) estimated the prevalence of OTC to range from 1 in 40,000 to 1 in 80,000. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Animal Model</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>The trait 'sparse fur' (spf) in the mouse is due to OTC deficiency. X-linkage was confirmed indirectly by the demonstration of DeMars et al. (1976) that the same enzyme deficiency is X-linked in the mouse. </p><p>Extracts of liver from hemizygous affected mice with the X-linked spf(ash) (sparse fur, abnormal skin and hair) mutation have 5 to 10% of normal OTC activity, yet the homogeneous enzyme isolated from these extracts is identical to that in controls. Rosenberg et al. (1983) found that the mRNA from mutant livers programs the synthesis of 2 distinct OTC precursor polypeptides: one normal in size, the other elongated. Only the normal one is assembled into the active trimeric enzyme. The novel phenotype likely results from a mutation in the structural gene for OTC, leading to aberrant splicing of mRNA and formation of an altered precursor that cannot undergo proper posttranslational modification. </p><p>In the 'sparse fur' mouse, Veres et al. (1987) identified a mutation in the OTC gene (see also Ohtake et al., 1986). </p><p>Cavard et al. (1988) successfully corrected OTC deficiency in the mouse by injection of rat OTC cDNA linked to the SV40 early promoter into fertilized eggs. </p><p>Morsy et al. (1996) achieved significant improvement of OTC deficiency in a mouse model through adenovirus-mediated gene transfer of the human OTC cDNA. Substantial reduction in orotic aciduria was observed within 24 hours of treatment. Metabolic correction was later associated with phenotypic correction and moderate increase in enzymatic activity. In an effort to identify the level of gene expression required to achieve wildtype levels of enzyme activity, Morsy et al. (1996) uncovered a dominant-negative effect of the endogenous mutant protein on the activity of the delivered recombinant wildtype protein. The authors stated that this phenomenon is relevant to homomultimeric protein defects, such as OTC deficiency. </p>
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>See Also:</strong>
</span>
</h4>
<span class="mim-text-font">
Amir et al. (1982); Batshaw et al. (1980); Cathelineau et al. (1974);
Gelehrter and Rosenberg (1975); Harding et al. (1984); Herrin and
McCredie (1969); Hokanson et al. (1978); Holzgreve and Golbus (1984);
Hoogenraad et al. (1983); Hopkins et al. (1969); Kodama et al.
(1986); Nussbaum et al. (1986); Old et al. (1985); Qureshi et al.
(1979); Rodeck et al. (1982); Schwartz et al. (1986); Shapiro et al.
(1980); Shih et al. (1978); Snodgrass et al. (1978); Stoll et al.
(1978); Sunshine et al. (1972); Wareham et al. (1987); Wettke-Schafer
and Kantner (1983); Yudkoff et al. (1980)
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
</span>
</h4>
<div>
<p />
</div>
<div>
<ol>
<li>
<p class="mim-text-font">
Amir, J., Alpert, G., Statter, M., Gutman, A., Reisner, S. H.
<strong>Intracranial haemorrhage in siblings and ornithine transcarbamylase deficiency.</strong>
Acta Paediat. Scand. 71: 671-673, 1982.
[PubMed: 7136688]
[Full Text: https://doi.org/10.1111/j.1651-2227.1982.tb09497.x]
</p>
</li>
<li>
<p class="mim-text-font">
Anadiotis, G., Ierardi-Curto, L., Kaplan, P. B., Berry, G. T.
<strong>Ornithine transcarbamylase deficiency and pancreatitis.</strong>
J. Pediat. 138: 123-124, 2001.
[PubMed: 11148526]
[Full Text: https://doi.org/10.1067/mpd.2001.109792]
</p>
</li>
<li>
<p class="mim-text-font">
Arn, P. H., Hauser, E. R., Thomas, G. H., Herman, G., Hess, D., Brusilow, S. W.
<strong>Hyperammonemia in women with a mutation at the ornithine carbamoyltransferase locus: a cause of postpartum coma.</strong>
New Eng. J. Med. 322: 1652-1655, 1990.
[PubMed: 2342525]
[Full Text: https://doi.org/10.1056/NEJM199006073222307]
</p>
</li>
<li>
<p class="mim-text-font">
Arn, P., Hauser, B., Maestri, N., Herman, G., Thomas, G. H., Brusilow, S. W.
<strong>Hyperammonemic coma in adult females heterozygous at the ornithine transcarbamylase locus (OTCDH). (Abstract)</strong>
Am. J. Hum. Genet. 45 (suppl.): A3, 1989.
</p>
</li>
<li>
<p class="mim-text-font">
Batshaw, M. L., Brusilow, S., Waber, L., Blom, W., Brubakk, A. M., Burton, B. K., Cann, H. M., Kerr, D., Mamunes, P., Matalon, R., Myerberg, D., Schafer, I. A.
<strong>Treatment of inborn errors of urea synthesis: activation of alternative pathways of waste nitrogen synthesis and excretion.</strong>
New Eng. J. Med. 306: 1387-1392, 1982.
[PubMed: 7078580]
[Full Text: https://doi.org/10.1056/NEJM198206103062303]
</p>
</li>
<li>
<p class="mim-text-font">
Batshaw, M. L., Roan, Y., Jung, A. L., Rosenberg, L. A., Brusilow, S. W.
<strong>Cerebral dysfunction in asymptomatic carriers of ornithine transcarbamylase deficiency.</strong>
New Eng. J. Med. 302: 482-485, 1980.
[PubMed: 7351973]
[Full Text: https://doi.org/10.1056/NEJM198002283020902]
</p>
</li>
<li>
<p class="mim-text-font">
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: 25135652]
[Full Text: https://doi.org/10.1016/j.ymgme.2014.08.001]
</p>
</li>
<li>
<p class="mim-text-font">
Bowling, F., McGown, I., McGill, J., Cowley, D., Tuchman, M.
<strong>Maternal gonadal mosaicism causing ornithine transcarbamylase deficiency.</strong>
Am. J. Med. Genet. 85: 452-454, 1999.
[PubMed: 10405441]
[Full Text: https://doi.org/10.1002/(sici)1096-8628(19990827)85:5&lt;452::aid-ajmg4&gt;3.0.co;2-4]
</p>
</li>
<li>
<p class="mim-text-font">
Brusilow, S. W., Danney, M., Waber, L. J., Batshaw, M., Burton, B., Levitsky, L., Roth, K., McKeethren, C., Ward, J.
<strong>Treatment of episodic hyperammonemia in children with inborn errors of urea synthesis.</strong>
New Eng. J. Med. 310: 1630-1634, 1984.
[PubMed: 6427608]
[Full Text: https://doi.org/10.1056/NEJM198406213102503]
</p>
</li>
<li>
<p class="mim-text-font">
Bruton, C. J., Corsellis, J. A. N., Russell, A.
<strong>Hereditary hyperammonemia.</strong>
Brain 93: 423-434, 1970.
[PubMed: 5310321]
[Full Text: https://doi.org/10.1093/brain/93.2.423]
</p>
</li>
<li>
<p class="mim-text-font">
Burdakin, J. H., Norum, R. A.
<strong>Recombination between loci for ornithine transcarbamylase (OTC) deficiency and G6PD. (Abstract)</strong>
Am. J. Hum. Genet. 33: 38A, 1981.
</p>
</li>
<li>
<p class="mim-text-font">
Campbell, A. G. M., Rosenberg, L. E., Snodgrass, P. J., Nuzum, C. T.
<strong>Lethal neonatal hyperammonaemia due to complete ornithine-transcarbamylase deficiency. (Letter)</strong>
Lancet 298: 217-218, 1971. Note: Originally Volume II.
[PubMed: 4104881]
[Full Text: https://doi.org/10.1016/s0140-6736(71)90931-7]
</p>
</li>
<li>
<p class="mim-text-font">
Campbell, A. G. M., Rosenberg, L. E., Snodgrass, P. J., Nuzum, C. T.
<strong>Ornithine transcarbamylase deficiency: a cause of lethal neonatal hyperammonemia in males.</strong>
New Eng. J. Med. 288: 1-6, 1973.
[PubMed: 4681895]
[Full Text: https://doi.org/10.1056/NEJM197301042880101]
</p>
</li>
<li>
<p class="mim-text-font">
Cathelineau, L., Saudubray, J.-M., Polonovski, C.
<strong>Heterogeneous mutations of the structural gene of human ornithine carbamyltransferase as observed in five personal cases.</strong>
Enzyme 18: 103-113, 1974.
[PubMed: 4852265]
[Full Text: https://doi.org/10.1159/000459417]
</p>
</li>
<li>
<p class="mim-text-font">
Cavard, C., Grimber, G., Dubois, N., Chasse, J.-F., Bennoun, M., Minet-Thuriaux, M., Kamoun, P., Briand, P.
<strong>Correction of mouse ornithine transcarbamylase deficiency by gene transfer into the germ line.</strong>
Nucleic Acids Res. 16: 2099-2110, 1988.
[PubMed: 3162766]
[Full Text: https://doi.org/10.1093/nar/16.5.2099]
</p>
</li>
<li>
<p class="mim-text-font">
DeMars, R., LeVan, S. L., Trend, B. L., Russell, L. B.
<strong>Abnormal ornithine carbamyltransferase in mice having the sparse-fur mutation.</strong>
Proc. Nat. Acad. Sci. 73: 1693-1697, 1976.
[PubMed: 5727]
[Full Text: https://doi.org/10.1073/pnas.73.5.1693]
</p>
</li>
<li>
<p class="mim-text-font">
Drogari, E., Leonard, J. V.
<strong>Late onset ornithine carbamoyl transferase deficiency in males.</strong>
Arch. Dis. Child. 63: 1363-1367, 1988.
[PubMed: 3202644]
[Full Text: https://doi.org/10.1136/adc.63.11.1363]
</p>
</li>
<li>
<p class="mim-text-font">
Finkelstein, J. E., Hauser, E., Brusilow, S. W.
<strong>Late onset ornithine transcarbamylase deficiency (OTCD) in males. (Abstract)</strong>
Am. J. Hum. Genet. 45 (suppl.): A5, 1989.
</p>
</li>
<li>
<p class="mim-text-font">
Finkelstein, J. E., Hauser, E. R., Leonard, C. O., Brusilow, S. W.
<strong>Late-onset ornithine transcarbamylase deficiency in male patients.</strong>
J. Pediat. 117: 897-902, 1990. Note: Erratum: J. Pediat. 118: 326 only, 1991.
[PubMed: 2246687]
[Full Text: https://doi.org/10.1016/s0022-3476(05)80129-5]
</p>
</li>
<li>
<p class="mim-text-font">
Fox, J. E., Hack, A. M., Fenton, W. A., Golbus, M. S., Winter, S., Kalousek, F., Rozen, R., Brusilow, S. W., Rosenberg, L. E.
<strong>Prenatal diagnosis of ornithine transcarbamylase deficiency with use of DNA polymorphisms.</strong>
New Eng. J. Med. 315: 1205-1208, 1986.
[PubMed: 3762643]
[Full Text: https://doi.org/10.1056/NEJM198611063151907]
</p>
</li>
<li>
<p class="mim-text-font">
Fox, J. E., Hack, A. M., Fenton, W. A., Rosenberg, L. E.
<strong>Identification and application of additional restriction fragment length polymorphisms at the human ornithine transcarbamylase locus.</strong>
Am. J. Hum. Genet. 38: 841-847, 1986.
[PubMed: 3014867]
</p>
</li>
<li>
<p class="mim-text-font">
Gelehrter, T. D., Rosenberg, L. E.
<strong>Ornithine transcarbamylase deficiency: unsuccessful therapy of neonatal hyperammonemia with N-carbamyl-L-glutamate and L-arginine.</strong>
New Eng. J. Med. 292: 351-352, 1975.
[PubMed: 1117963]
[Full Text: https://doi.org/10.1056/NEJM197502132920708]
</p>
</li>
<li>
<p class="mim-text-font">
Gilchrist, J. M., Coleman, R. A.
<strong>Ornithine transcarbamylase deficiency: adult onset of severe symptoms.</strong>
Ann. Intern. Med. 106: 556-558, 1987.
[PubMed: 3826955]
[Full Text: https://doi.org/10.7326/0003-4819-106-4-556]
</p>
</li>
<li>
<p class="mim-text-font">
Goldblum, O. M., Brusilow, S. W., Maldonado, Y. A., Farmer, E. R.
<strong>Neonatal citrullinemia associated with cutaneous manifestations and arginine deficiency.</strong>
J. Am. Acad. Derm. 14: 321-326, 1986.
[PubMed: 3950131]
[Full Text: https://doi.org/10.1016/s0190-9622(86)70035-2]
</p>
</li>
<li>
<p class="mim-text-font">
Grompe, M., Caskey, C. T., Fenwick, R. G.
<strong>Improved molecular diagnostics for ornithine transcarbamylase deficiency.</strong>
Am. J. Hum. Genet. 48: 212-222, 1991.
[PubMed: 1671317]
</p>
</li>
<li>
<p class="mim-text-font">
Grompe, M., Muzny, D. M., Caskey, C. T.
<strong>Scanning detections of mutations in human ornithine transcarbamylase deficiency (OTC) by chemical mismatch cleavage. (Abstract)</strong>
Am. J. Hum. Genet. 45 (suppl.): A192, 1989.
</p>
</li>
<li>
<p class="mim-text-font">
Hamano, Y., Kodama, H., Fujikawa, Y., Tanaka, Y., Nishimura, K., Yanagisawa, M.
<strong>Use of immunocytochemical analysis of a duodenal biopsy specimen to identify a carrier of ornithine transcarbamylase deficiency.</strong>
New Eng. J. Med. 318: 1521-1523, 1988.
[PubMed: 3367962]
[Full Text: https://doi.org/10.1056/NEJM198806093182307]
</p>
</li>
<li>
<p class="mim-text-font">
Harding, B. N., Leonard, J. V., Erdohazi, M.
<strong>Ornithine carbamoyl transferase deficiency: a neuropathological study.</strong>
Europ. J. Pediat. 141: 215-220, 1984.
[PubMed: 6734670]
[Full Text: https://doi.org/10.1007/BF00572763]
</p>
</li>
<li>
<p class="mim-text-font">
Hauser, E. R., Finkelstein, J. E., Valle, D., Brusilow, S. W.
<strong>Allopurinol-induced orotidinuria: a test for mutations at the ornithine carbamoyltransferase locus in women.</strong>
New Eng. J. Med. 322: 1641-1645, 1990. Note: Erratum: New Eng. J. Med. 336: 1335 only, 1997.
[PubMed: 2342523]
[Full Text: https://doi.org/10.1056/NEJM199006073222305]
</p>
</li>
<li>
<p class="mim-text-font">
Herrin, J. T., McCredie, D. A.
<strong>Peritoneal dialysis in the reduction of blood ammonia levels in a case of hyperammonaemia.</strong>
Arch. Dis. Child. 44: 149-151, 1969.
[PubMed: 5779425]
[Full Text: https://doi.org/10.1136/adc.44.234.149]
</p>
</li>
<li>
<p class="mim-text-font">
Hjelm, M., de Silva, L. V. K., Seakins, J. W. T., Oberholzer, V. G., Rolles, C. J.
<strong>Evidence of inherited urea cycle defect in a case of fatal valproate toxicity.</strong>
Brit. Med. J. 292: 23-24, 1986.
[PubMed: 3080051]
[Full Text: https://doi.org/10.1136/bmj.292.6512.23]
</p>
</li>
<li>
<p class="mim-text-font">
Hokanson, J. T., O'Brien, W. E., Idemoto, J., Schafer, I. A.
<strong>Carrier detection in ornithine transcarbamylase deficiency.</strong>
J. Pediat. 93: 75-78, 1978.
[PubMed: 650350]
[Full Text: https://doi.org/10.1016/s0022-3476(78)80606-4]
</p>
</li>
<li>
<p class="mim-text-font">
Holmes, A. K., Fowler, B., Sardharwalla, I. B.
<strong>Late-onset ornithine carbamyl transferase deficiency in a male patient: detailed enzyme studies.</strong>
J. Inherit. Metab. Dis. 10 (suppl. 2): 299-301, 1987.
</p>
</li>
<li>
<p class="mim-text-font">
Holzgreve, W., Golbus, M. S.
<strong>Prenatal diagnosis of ornithine transcarbamylase deficiency utilizing fetal liver biopsy.</strong>
Am. J. Hum. Genet. 36: 320-328, 1984.
[PubMed: 6711559]
</p>
</li>
<li>
<p class="mim-text-font">
Honeycutt, D., Callahan, K., Rutledge, L., Evans, B.
<strong>Heterozygote ornithine transcarbamylase deficiency presenting as symptomatic hyperammonemia during initiation of valproate therapy.</strong>
Neurology 42: 666-668, 1992.
[PubMed: 1549234]
[Full Text: https://doi.org/10.1212/wnl.42.3.666]
</p>
</li>
<li>
<p class="mim-text-font">
Hoogenraad, N., de Martinis, M. L., Danks, D. M.
<strong>Immunological evidence for an ornithine transcarbamylase lesion resulting in the formation of enzyme with smaller protein subunits.</strong>
J. Inherit. Metab. Dis. 6: 149-152, 1983.
[PubMed: 6422154]
[Full Text: https://doi.org/10.1007/BF02310869]
</p>
</li>
<li>
<p class="mim-text-font">
Hopkins, I. J., Connelly, J. F., Dawson, A. G., Hird, F. J., Maddison, T. G.
<strong>Hyperammonaemia due to ornithine transcarbamylase deficiency.</strong>
Arch. Dis. Child. 44: 143-148, 1969.
[PubMed: 21032452]
[Full Text: https://doi.org/10.1136/adc.44.234.143]
</p>
</li>
<li>
<p class="mim-text-font">
Iijima, H., Kubota, M.
<strong>A simple screening method for heterozygous female patients with ornithine transcarbamylase deficiency.</strong>
Molec. Genet. Metab. 137: 301-307, 2022.
[PubMed: 36252454]
[Full Text: https://doi.org/10.1016/j.ymgme.2022.10.003]
</p>
</li>
<li>
<p class="mim-text-font">
Jang, Y. J., LaBella, A. L., Feeney, T. P., Braverman, N., Tuchman, M., Morizono, H., Ah Mew, N., Caldovic, L.
<strong>Disease-causing mutations in the promoter and enhancer of the ornithine transcarbamylase gene.</strong>
Hum. Mutat. 39: 527-536, 2018.
[PubMed: 29282796]
[Full Text: https://doi.org/10.1002/humu.23394]
</p>
</li>
<li>
<p class="mim-text-font">
Kay, J. D. S., Hilton-Jones, D., Hyman, N.
<strong>Valproate toxicity and ornithine carbamoyltransferase deficiency. (Letter)</strong>
Lancet 328: 1283-1284, 1986. Note: Originally Volume II.
[PubMed: 2878165]
[Full Text: https://doi.org/10.1016/s0140-6736(86)92714-5]
</p>
</li>
<li>
<p class="mim-text-font">
Kline, J. J., Hug, G., Schubert, W. K., Berry, H.
<strong>Arginine deficiency syndrome: its occurrence in carbamyl phosphate synthetase deficiency.</strong>
Am. J. Dis. Child. 135: 437-442, 1981.
[PubMed: 7234771]
</p>
</li>
<li>
<p class="mim-text-font">
Kodama, H., Ohtake, A., Mori, M., Okabe, I., Tatibana, M., Kamoshita, S.
<strong>Ornithine transcarbamylase deficiency: a case with a truncated enzyme precursor and a case with undetectable mRNA activity.</strong>
J. Inherit. Metab. Dis. 9: 175-185, 1986.
[PubMed: 3091923]
[Full Text: https://doi.org/10.1007/BF01799456]
</p>
</li>
<li>
<p class="mim-text-font">
Kornfeld, M., Woodfin, B. M., Papile, L., Davis, L. E., Bernard, L. R.
<strong>Neuropathology of ornithine carbamyl transferase deficiency.</strong>
Acta Neuropath. 65: 261-264, 1985.
[PubMed: 3976361]
[Full Text: https://doi.org/10.1007/BF00687006]
</p>
</li>
<li>
<p class="mim-text-font">
Korson, M. S., Lillehei, C. W., Vacanti, J. P., Levy, H. L.
<strong>Liver transplantation for ornithine transcarbamylase deficiency (OTCD). (Abstract)</strong>
Am. J. Hum. Genet. 45 (suppl.): A8, 1989.
</p>
</li>
<li>
<p class="mim-text-font">
Krieger, I., Snodgrass, P. J., Roskamp, J.
<strong>Atypical clinical course of ornithine transcarbamylase deficiency due to a new mutant (comparison with Reye&#x27;s disease).</strong>
J. Clin. Endocr. Metab. 48: 388-392, 1979.
[PubMed: 429491]
[Full Text: https://doi.org/10.1210/jcem-48-3-388]
</p>
</li>
<li>
<p class="mim-text-font">
Lee, J.-Y., Chang, S.-E., Suh, C.-W., Choi, J.-H., Sung, K.-J., Moon, K.-C., Koh, J.-K.
<strong>A case of acrodermatitis enteropathica-like dermatosis caused by ornithine transcarbamylase deficiency.</strong>
J. Am. Acad. Derm. 46: 965-967, 2002.
[PubMed: 12063505]
[Full Text: https://doi.org/10.1067/mjd.2002.120595]
</p>
</li>
<li>
<p class="mim-text-font">
Levin, B., Abraham, J. M., Oberholzer, V. G., Burgess, E. A.
<strong>Hyperammonaemia: a deficiency of liver ornithine transcarbamylase. Occurrence in mother and child.</strong>
Arch. Dis. Child. 44: 152-161, 1969.
[PubMed: 5779426]
[Full Text: https://doi.org/10.1136/adc.44.234.152]
</p>
</li>
<li>
<p class="mim-text-font">
Lien, J., Nyhan, W. L., Barshop, B. A.
<strong>Fatal initial adult-onset presentation of urea cycle defect.</strong>
Arch. Neurol. 64: 1777-1779, 2007.
[PubMed: 18071043]
[Full Text: https://doi.org/10.1001/archneur.64.12.1777]
</p>
</li>
<li>
<p class="mim-text-font">
Lo, R. S., Cromie, G. A., Tang, M., Teng, K., Owens, K., Sirr, A., Kutz, J. N., Morizono, H., Caldovic, L., Ah Mew, N., Gropman, A., Dudley, A. M.
<strong>The functional impact of 1,570 individual amino acid substitutions in human OTC.</strong>
Am. J. Hum. Genet. 110: 863-879, 2023.
[PubMed: 37146589]
[Full Text: https://doi.org/10.1016/j.ajhg.2023.03.019]
</p>
</li>
<li>
<p class="mim-text-font">
Lopes-Marques, M., Pacheco, A. R., Peixoto, M. J., Cardoso, A. R., Serrano, C., Amorim, A., Prata, M. J., Cooper, D. N., Azevedo, L.
<strong>Common polymorphic OTC variants can act as genetic modifiers of enzymatic activity.</strong>
Hum. Mutat. 42: 978-989, 2021.
[PubMed: 34015158]
[Full Text: https://doi.org/10.1002/humu.24221]
</p>
</li>
<li>
<p class="mim-text-font">
Maddalena, A., Sosnoski, D. M., Berry, G. T., Nussbaum, R. L.
<strong>Mosaicism for an intragenic deletion in a boy with mild ornithine transcarbamylase deficiency.</strong>
New Eng. J. Med. 319: 999-1003, 1988.
[PubMed: 2843770]
[Full Text: https://doi.org/10.1056/NEJM198810133191507]
</p>
</li>
<li>
<p class="mim-text-font">
Maddalena, A., Spence, J. E., O'Brien, W. E., Nussbaum, R. L.
<strong>Characterization of point mutations in the same arginine codon in three unrelated patients with ornithine transcarbamylase deficiency.</strong>
J. Clin. Invest. 82: 1353-1358, 1988.
[PubMed: 3170748]
[Full Text: https://doi.org/10.1172/JCI113738]
</p>
</li>
<li>
<p class="mim-text-font">
Maestri, N. E., Brusilow, S. W., Clissold, D. B., Bassett, S. S.
<strong>Long-term treatment of girls with ornithine transcarbamylase deficiency.</strong>
New Eng. J. Med. 335: 855-859, 1996.
[PubMed: 8778603]
[Full Text: https://doi.org/10.1056/NEJM199609193351204]
</p>
</li>
<li>
<p class="mim-text-font">
Maestri, N. E., Hauser, E. R., Bartholomew, D., Brusilow, S. W.
<strong>Prospective treatment of urea cycle disorders.</strong>
J. Pediat. 119: 923-928, 1991.
[PubMed: 1720458]
[Full Text: https://doi.org/10.1016/s0022-3476(05)83044-6]
</p>
</li>
<li>
<p class="mim-text-font">
Matsuda, I., Arashima, S., Nambu, H., Takekoshi, Y., Anakura, M.
<strong>Hyperammonemia due to a mutant enzyme of ornithine transcarbamylase.</strong>
Pediatrics 48: 595-600, 1971.
[PubMed: 5114747]
</p>
</li>
<li>
<p class="mim-text-font">
Matsuda, I., Nagata, N., Matsuura, T., Oyanagi, K., Tada, K., Narisawa, K., Kitagawa, T., Sakiyama, T., Yamashita, F., Yoshino, M.
<strong>Retrospective survey of urea cycle disorders: Part 1. Clinical and laboratory observations of thirty-two Japanese male patients with ornithine transcarbamylase deficiency.</strong>
Am. J. Med. Genet. 38: 85-89, 1991.
[PubMed: 2012137]
[Full Text: https://doi.org/10.1002/ajmg.1320380119]
</p>
</li>
<li>
<p class="mim-text-font">
McCullough, B. A., Yudkoff, M., Batshaw, M. L., Wilson, J. M., Raper, S. E., Tuchman, M.
<strong>Genotype spectrum of ornithine transcarbamylase deficiency: correlation with the clinical and biochemical phenotype.</strong>
Am. J. Med. Genet. 93: 313-319, 2000.
[PubMed: 10946359]
[Full Text: https://doi.org/10.1002/1096-8628(20000814)93:4&lt;313::aid-ajmg11&gt;3.0.co;2-m]
</p>
</li>
<li>
<p class="mim-text-font">
Michels, V. V., Potts, E., Walser, M., Beaudet, A. L.
<strong>Ornithine transcarbamylase deficiency: long-term survival.</strong>
Clin. Genet. 22: 211-214, 1982.
[PubMed: 7151305]
[Full Text: https://doi.org/10.1111/j.1399-0004.1982.tb01435.x]
</p>
</li>
<li>
<p class="mim-text-font">
Morsy, M. A., Zhao, J. Z., Ngo, T. T., Warman, A. W., O'Brien, W. E., Graham, F. L., Caskey, C. T.
<strong>Patient selection may affect gene therapy success: dominant negative effects observed for ornithine transcarbamylase in mouse and human hepatocytes.</strong>
J. Clin. Invest. 97: 826-832, 1996.
[PubMed: 8609240]
[Full Text: https://doi.org/10.1172/JCI118482]
</p>
</li>
<li>
<p class="mim-text-font">
Nagata, N., Matsuda, I., Oyanagi, K.
<strong>Estimated frequency of urea cycle enzymopathies in Japan. (Letter)</strong>
Am. J. Med. Genet. 39: 228-229, 1991.
[PubMed: 2063931]
[Full Text: https://doi.org/10.1002/ajmg.1320390226]
</p>
</li>
<li>
<p class="mim-text-font">
Nussbaum, R. L., Boggs, B. A., Beaudet, A. L., Doyle, S., Potter, J. L., O'Brien, W. E.
<strong>New mutation and prenatal diagnosis in ornithine transcarbamylase deficiency.</strong>
Am. J. Hum. Genet. 38: 149-158, 1986.
[PubMed: 3004207]
</p>
</li>
<li>
<p class="mim-text-font">
Ohtake, A., Takayanagi, M., Yamamoto, S., Kakinuma, H., Nakajima, H., Tatibana, M., Mori, M.
<strong>Molecular basis of ornithine transcarbamylase deficiency in spf and spf-ash mutant mice.</strong>
J. Inherit. Metab. Dis. 9: 289-291, 1986.
[PubMed: 3099076]
[Full Text: https://doi.org/10.1007/BF01799667]
</p>
</li>
<li>
<p class="mim-text-font">
Oizumi, J., Ng, W. G., Koch, R., Shaw, K. N. F., Sweetman, L., Velazquez, A., Donnell, G. N.
<strong>Partial ornithine transcarbamylase deficiency associated with recurrent hyperammonemia, lethargy and depressed sensorium.</strong>
Clin. Genet. 25: 538-542, 1984.
[PubMed: 6733950]
[Full Text: https://doi.org/10.1111/j.1399-0004.1984.tb00498.x]
</p>
</li>
<li>
<p class="mim-text-font">
Old, J. M., Briand, P. L., Purvis-Smith, S., Howard, N. J., Wilcken, B., Hammond, J., Pearson, P., Cathelineau, L., Williamson, R., Davies, K. E.
<strong>Prenatal exclusion of ornithine transcarbamylase deficiency by direct gene analysis.</strong>
Lancet 325: 73-75, 1985. Note: Originally Volume I.
[PubMed: 2857026]
[Full Text: https://doi.org/10.1016/s0140-6736(85)91966-x]
</p>
</li>
<li>
<p class="mim-text-font">
Pelet, A., Rotig, A., Bonaiti-Pellie, C., Rabier, D., Cormier, V., Toumas, E., Hentzen, D., Saudubray, J.-M., Munnich, A.
<strong>Carrier detection in a partially dominant X-linked disease: ornithine transcarbamylase deficiency.</strong>
Hum. Genet. 84: 167-171, 1990.
[PubMed: 2298453]
[Full Text: https://doi.org/10.1007/BF00208934]
</p>
</li>
<li>
<p class="mim-text-font">
Pembrey, M. E., Old, J. M., Leonard, J. V., Rodeck, C. H., Warren, R., Davies, K. E.
<strong>Prenatal diagnosis of ornithine carbamoyl transferase deficiency using a gene specific probe.</strong>
J. Med. Genet. 22: 462-465, 1985.
[PubMed: 3001312]
[Full Text: https://doi.org/10.1136/jmg.22.6.462]
</p>
</li>
<li>
<p class="mim-text-font">
Qureshi, I. A., Letarte, J., Ouellet, R.
<strong>Ornithine transcarbamylase deficiency in mutant mice. I. Studies on the characterization of enzyme defect and suitability as animal model of human disease.</strong>
Pediat. Res. 13: 807-811, 1979.
[PubMed: 481951]
[Full Text: https://doi.org/10.1203/00006450-197907000-00003]
</p>
</li>
<li>
<p class="mim-text-font">
Ricciuti, F. C., Gelehrter, T. D., Rosenberg, L. E.
<strong>X-chromosome inactivation in human liver: confirmation of X-linkage of ornithine transcarbamylase.</strong>
Am. J. Hum. Genet. 28: 332-338, 1976.
[PubMed: 941900]
</p>
</li>
<li>
<p class="mim-text-font">
Rodeck, C. H., Patrick, A. D., Pembrey, M. E., Tzannatos, C., Whitfield, A. E.
<strong>Fetal liver biopsy for prenatal diagnosis of ornithine carbamyl transferase deficiency.</strong>
Lancet 320: 297-300, 1982. Note: Originally Volume II.
[PubMed: 6124717]
[Full Text: https://doi.org/10.1016/s0140-6736(82)90272-0]
</p>
</li>
<li>
<p class="mim-text-font">
Rosenberg, L. E., Kalousek, F., Orsulak, M. D.
<strong>Biogenesis of ornithine transcarbamylase in spf(ash) mutant mice: two cytoplasmic precursors, one mitochondrial enzyme.</strong>
Science 222: 426-428, 1983.
[PubMed: 6623083]
[Full Text: https://doi.org/10.1126/science.6623083]
</p>
</li>
<li>
<p class="mim-text-font">
Rowe, P. C., Newman, S. L., Brusilow, S. W.
<strong>Natural history of symptomatic partial ornithine transcarbamylase deficiency.</strong>
New Eng. J. Med. 314: 541-547, 1986.
[PubMed: 3945292]
[Full Text: https://doi.org/10.1056/NEJM198602273140903]
</p>
</li>
<li>
<p class="mim-text-font">
Rozen, R., Fox, J., Fenton, W. A., Horwich, A. L., Rosenberg, L. E.
<strong>Gene deletion and restriction fragment length polymorphisms at the human ornithine transcarbamylase locus.</strong>
Nature 313: 815-817, 1985.
[PubMed: 2983225]
[Full Text: https://doi.org/10.1038/313815a0]
</p>
</li>
<li>
<p class="mim-text-font">
Russell, A., Levin, B., Oberholzer, V. G., Sinclair, L.
<strong>Hyperammonaemia. A new instance of an inborn enzymatic defect of the biosynthesis of urea.</strong>
Lancet 280: 699-700, 1962. Note: Originally Volume II.
[PubMed: 13975632]
[Full Text: https://doi.org/10.1016/s0140-6736(62)90508-1]
</p>
</li>
<li>
<p class="mim-text-font">
Schwartz, M., Christensen, E., Christensen, N. C., Skovby, F., Davies, K. E., Old, J. M.
<strong>Detection and exclusion of carriers of ornithine transcarbamylase deficiency by RFLP analysis.</strong>
Clin. Genet. 29: 449-452, 1986.
[PubMed: 3017613]
[Full Text: https://doi.org/10.1111/j.1399-0004.1986.tb00520.x]
</p>
</li>
<li>
<p class="mim-text-font">
Scott, C. R., Chiang-Teng, C., Goodman, S. I., Greensher, A., Mace, J. W.
<strong>X-linked transmission of ornithine-transcarbamylase deficiency. (Letter)</strong>
Lancet 300: 1148 only, 1972. Note: Originally Volume II.
[PubMed: 4117228]
[Full Text: https://doi.org/10.1016/s0140-6736(72)92756-0]
</p>
</li>
<li>
<p class="mim-text-font">
Shapiro, J. M., Schaffner, F., Tallan, H. H., Gaull, G. E.
<strong>Mitochondrial abnormalities of liver in primary ornithine transcarbamylase deficiency.</strong>
Pediat. Res. 14: 735-759, 1980.
[PubMed: 7383749]
[Full Text: https://doi.org/10.1203/00006450-198005000-00006]
</p>
</li>
<li>
<p class="mim-text-font">
Shih, V. E., Berson, E. L., Mandell, R., Schmidt, S. Y.
<strong>Ornithine ketoacid transaminase deficiency in gyrate atrophy of the choroid and retina.</strong>
Am. J. Hum. Genet. 30: 174-179, 1978.
[PubMed: 655164]
</p>
</li>
<li>
<p class="mim-text-font">
Short, E. M., Conn, H. O., Snodgrass, P. J., Campbell, A. G. M., Rosenberg, L. E.
<strong>Evidence for X-linked dominant inheritance of ornithine transcarbamylase deficiency.</strong>
New Eng. J. Med. 288: 7-12, 1973.
[PubMed: 4681915]
[Full Text: https://doi.org/10.1056/NEJM197301042880102]
</p>
</li>
<li>
<p class="mim-text-font">
Snodgrass, P. J., Wappner, R. S., Brandt, I. K.
<strong>White cell ornithine transcarbamylase activity cannot detect the liver enzyme deficiency. (Letter)</strong>
Pediat. Res. 12: 873, 1978.
[PubMed: 683745]
[Full Text: https://doi.org/10.1203/00006450-197808000-00014]
</p>
</li>
<li>
<p class="mim-text-font">
Stoll, C., Bieth, R., Dreyfus, J., Flori, E., Lutz, P., Levy, J.-M.
<strong>Une nouvelle famille avec mutation du gene de structure de l&#x27;ornithine carbamyltransferase humaine.</strong>
Arch. Franc. Pediat. 35: 512-518, 1978.
[PubMed: 678030]
</p>
</li>
<li>
<p class="mim-text-font">
Sunshine, P., Lindenbaum, J. E., Levy, H. L., Freeman, J. M.
<strong>Hyperammonemia due to a defect in hepatic ornithine transcarbamylase.</strong>
Pediatrics 50: 100-111, 1972.
[PubMed: 5038084]
</p>
</li>
<li>
<p class="mim-text-font">
Testai, F. D., Gorelick, P. B.
<strong>Inherited metabolic disorders and stroke part 2: homocystinuria, organic acidurias, and urea cycle disorders.</strong>
Arch. Neurol. 67: 148-153, 2010.
[PubMed: 20142522]
[Full Text: https://doi.org/10.1001/archneurol.2009.333]
</p>
</li>
<li>
<p class="mim-text-font">
Thaler, M. M., Hoogenraad, N. J., Boswell, M.
<strong>Reye&#x27;s syndrome due to a novel protein-tolerant variant of ornithine-transcarbamylase deficiency.</strong>
Lancet 304: 438-440, 1974. Note: Originally Volume II.
[PubMed: 4137171]
[Full Text: https://doi.org/10.1016/s0140-6736(74)91819-4]
</p>
</li>
<li>
<p class="mim-text-font">
Torkzaban, M., Haddad, A., Baxter, J. K., Berghella, V., Gahl, W. A., Al-Kouatly, H.
<strong>Maternal ornithine transcarbamylase deficiency, a genetic condition associated with high maternal and neonatal mortality every clinician should know: a systematic review.</strong>
Am. J. Med. Genet. 179A: 2091-2100, 2019.
[PubMed: 31441224]
[Full Text: https://doi.org/10.1002/ajmg.a.61329]
</p>
</li>
<li>
<p class="mim-text-font">
Tripp, J. H., Hargreaves, T., Anthony, P. P., Searle, J. F., Miller, P., Leonard, J. V., Patrick, A. D., Oberholzer, V. G.
<strong>Sodium valproate and ornithine carbamyl transferase deficiency. (Letter)</strong>
Lancet 317: 1165-1166, 1981. Note: Originally Volume I.
[PubMed: 6112522]
[Full Text: https://doi.org/10.1016/s0140-6736(81)92338-2]
</p>
</li>
<li>
<p class="mim-text-font">
Tuchman, M., Plante, R. J., Garcia-Perez, M. A., Rubio, V.
<strong>Relative frequency of mutations causing ornithine transcarbamylase deficiency in 78 families.</strong>
Hum. Genet. 97: 274-276, 1996.
[PubMed: 8786061]
[Full Text: https://doi.org/10.1007/BF02185751]
</p>
</li>
<li>
<p class="mim-text-font">
Tuchman, M.
<strong>Mutations and polymorphisms in the human ornithine transcarbamylase gene.</strong>
Hum. Mutat. 2: 174-178, 1993.
[PubMed: 8364586]
[Full Text: https://doi.org/10.1002/humu.1380020304]
</p>
</li>
<li>
<p class="mim-text-font">
Veres, G., Gibbs, R. A., Scherer, S. E., Caskey, C. T.
<strong>The molecular basis of the sparse fur mouse mutation.</strong>
Science 237: 415-417, 1987.
[PubMed: 3603027]
[Full Text: https://doi.org/10.1126/science.3603027]
</p>
</li>
<li>
<p class="mim-text-font">
Wareham, K. A., Lyon, M. F., Glenister, P. H., Williams, E. D.
<strong>Age related reactivation of an X-linked gene.</strong>
Nature 327: 725-727, 1987.
[PubMed: 3600770]
[Full Text: https://doi.org/10.1038/327725a0]
</p>
</li>
<li>
<p class="mim-text-font">
Wettke-Schafer, R., Kantner, G.
<strong>X-linked dominant inherited diseases with lethality in hemizygous males.</strong>
Hum. Genet. 64: 1-23, 1983.
[PubMed: 6873941]
[Full Text: https://doi.org/10.1007/BF00289472]
</p>
</li>
<li>
<p class="mim-text-font">
Wilnai, Y., Blumenfeld, Y. J., Cusmano, K., Hintz, S. R., Alcorn, D., Benitz, W. E., Berquist, W. E., Bernstein, J. A., Castillo, R. O., Concepcion, W., Cowan, T. M., Cox, K. L., and 10 others.
<strong>Prenatal treatment of ornithine transcarbamylase deficiency.</strong>
Molec. Genet. Metab. 123: 297-300, 2018.
[PubMed: 29396029]
[Full Text: https://doi.org/10.1016/j.ymgme.2018.01.004]
</p>
</li>
<li>
<p class="mim-text-font">
Wilson, C. J., Lee, P. J., Leonard, J. V.
<strong>Plasma glutamine and ammonia concentrations in ornithine carbamoyltransferase deficiency and citrullinaemia.</strong>
J. Inherit. Metab. Dis. 24: 691-695, 2001.
[PubMed: 11804205]
[Full Text: https://doi.org/10.1023/a:1012995701589]
</p>
</li>
<li>
<p class="mim-text-font">
Yorifuji, T., Muroi, J., Uematsu, A., Tanaka, K., Kiwaki, K., Endo, F., Matsuda, I., Nagasaka, H., Furusho, K.
<strong>X-inactivation pattern in the liver of a manifesting female with ornithine transcarbamylase (OTC) deficiency.</strong>
Clin. Genet. 54: 349-353, 1998.
[PubMed: 9831349]
[Full Text: https://doi.org/10.1034/j.1399-0004.1998.5440415.x]
</p>
</li>
<li>
<p class="mim-text-font">
Yudkoff, M., Daikhin, Y., Nissim, I., Jawad, A., Wilson, J., Batshaw, M.
<strong>In vivo nitrogen metabolism in ornithine transcarbamylase deficiency.</strong>
J. Clin. Invest. 98: 2167-2173, 1996.
[PubMed: 8903337]
[Full Text: https://doi.org/10.1172/JCI119023]
</p>
</li>
<li>
<p class="mim-text-font">
Yudkoff, M., Yang, W., Snodgrass, P. J., Segal, S.
<strong>Ornithine transcarbamylase deficiency in a boy with normal development.</strong>
J. Pediat. 96: 441-443, 1980.
[PubMed: 7188954]
[Full Text: https://doi.org/10.1016/s0022-3476(80)80694-9]
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Hilary J. Vernon - updated : 08/09/2023<br>Hilary J. Vernon - updated : 02/21/2023<br>Hilary J. Vernon - updated : 11/16/2020<br>Hilary J. Vernon - updated : 05/19/2020<br>Ada Hamosh - updated : 1/7/2015<br>Cassandra L. Kniffin - updated : 10/11/2010<br>Cassandra L. Kniffin - updated : 3/31/2008<br>Cassandra L. Kniffin -updated : 10/10/2005<br>Cassandra L. Kniffin - reorganized : 12/4/2003<br>Gary A. Bellus - updated : 4/24/2003<br>Victor A. McKusick - updated : 2/21/2002<br>Ada Hamosh - updated : 1/30/2002<br>Ada Hamosh - updated : 1/23/2002<br>Ada Hamosh - updated : 5/16/2001<br>Ada Hamosh - updated : 4/23/2001<br>Victor A. McKusick - updated : 4/5/2001<br>Victor A. McKusick - updated : 2/23/2000<br>Sonja A. Rasmussen - updated : 10/1/1999<br>Victor A. McKusick - updated : 1/26/1999<br>Victor A. McKusick - updated : 6/18/1997<br>Victor A. McKusick - updated : 5/15/1997<br>Cynthia K. Ewing - updated : 10/8/1996
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Victor A. McKusick : 6/4/1986
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