3137 lines
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Entry
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- #243500 - ISOVALERIC ACIDEMIA; IVA
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- OMIM
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<p>
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<span class="h4">#243500</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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</li>
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<li role="presentation">
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<li role="presentation">
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<a href="/clinicalSynopsis/243500"><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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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#clinicalManagement">Clinical Management</a>
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<a href="#pathogenesis">Pathogenesis</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation">
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<a href="#seeAlso"><strong>See Also</strong></a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div style="display: table-cell;">External Links</div>
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</a>
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</h4>
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://clinicaltrials.gov/search?cond=ISOVALERIC ACIDEMIA" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=399&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK601614/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/3888" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://medlineplus.gov/genetics/condition/isovaleric-acidemia" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=243500[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div><a href="#mimNewbornScreeningFold" id="mimNewbornScreeningToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Information and resources for newborn screening and genetics."><span id="mimNewbornScreeningToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Newborn Screening</div>
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<div id="mimNewbornScreeningFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.acmg.net/PDFLibrary/C5.pdf" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Newborn Screening', 'domain': 'www.acmg.net'})">ACMG ACT Sheet</a></div><div style="margin-left: 0.5em;"><a href="https://www.acmg.net/PDFLibrary/C5-Algorithm.pdf" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Newborn Screening', 'domain': 'www.acmg.net'})">ACMG Algorithm</a></div>
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</div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=33" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/disease/DOID:14753" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="http://www.informatics.jax.org/disease/243500" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:14753" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimCellLines">
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<span class="panel-title">
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<span class="small">
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<a href="#mimCellLinesLinksFold" id="mimCellLinesLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimCellLinesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cell Lines</div>
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</a>
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</span>
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</div>
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<div id="mimCellLinesLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://catalog.coriell.org/Search?q=OmimNum:243500" 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>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</div>
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<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">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 87827003<br />
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<strong>ICD10CM:</strong> E71.110<br />
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<strong>ORPHA:</strong> 33<br />
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<strong>DO:</strong> 14753<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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243500
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</span>
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</span>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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ISOVALERIC ACIDEMIA; IVA
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<div>
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<h4>
|
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<span class="mim-font">
|
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ISOVALERIC ACID CoA DEHYDROGENASE DEFICIENCY<br />
|
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IVD DEFICIENCY
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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<div>
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<a id="phenotypeMap" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
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</h4>
|
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<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/15/98?start=-3&limit=10&highlight=98">
|
|
15q15.1
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Isovaleric acidemia
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/243500"> 243500 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
IVD
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607036"> 607036 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
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</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
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|
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<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/243500" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<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/243500" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/243500" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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|
|
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|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ABDOMEN </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Gastrointestinal </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Feeding refusal, especially aversion to protein <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855706&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855706</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">
|
|
|
|
- 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 /> -
|
|
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 /> -
|
|
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 /> -
|
|
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 /> -
|
|
Cerebellar hemorrhage (rare) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/75038005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">75038005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0149854&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0149854</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011695" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011695</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011695" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011695</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> METABOLIC FEATURES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Metabolic acidosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/59455009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">59455009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E87.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E87.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0220981&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0220981</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001942" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001942</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001942" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001942</a>]</span><br /> -
|
|
Ketoacidosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/56051008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">56051008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0220982&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0220982</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001993" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001993</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001993" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001993</a>]</span><br /> -
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Dehydration <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/34095006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">34095006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E86.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E86.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/276.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">276.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011175&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011175</a>, <a href="https://bioportal.bioontology.org/search?q=C2062903&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2062903</a>, <a href="https://bioportal.bioontology.org/search?q=C4284399&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4284399</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001944" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001944</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001944" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001944</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> HEMATOLOGY </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Thrombocytopenia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/415116008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">415116008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/302215000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">302215000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D69.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D69.6</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/287.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">287.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0392386&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0392386</a>, <a href="https://bioportal.bioontology.org/search?q=C0040034&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0040034</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001873" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001873</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001873" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001873</a>]</span><br /> -
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Leukopenia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/419188005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">419188005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/84828003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">84828003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D72.819" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D72.819</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/D72.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D72.81</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/288.50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">288.50</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/288.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">288.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0750394&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0750394</a>, <a href="https://bioportal.bioontology.org/search?q=C0023530&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023530</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001882" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001882</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001882" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001882</a>]</span><br /> -
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Pancytopenia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/127034005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">127034005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D61.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D61.81</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/284.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">284.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0030312&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0030312</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001876" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001876</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001876" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001876</a>]</span><br /> -
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Hypoplastic bone marrow <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/167928002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">167928002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855710&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855710</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005528" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005528</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005528" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005528</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> LABORATORY ABNORMALITIES </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Isovalericacidemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/87827003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">87827003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E71.110" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E71.110</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0268575&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0268575</a>, <a href="https://bioportal.bioontology.org/search?q=C5399976&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5399976</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0033148" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0033148</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0033148" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0033148</a>]</span><br /> -
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Isovalericaciduria <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855707&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855707</a>]</span><br /> -
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Isovalerylglycinuria <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855708&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855708</a>]</span><br /> -
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Deficiency of mitochondrial isovaleryl-CoA dehydrogenase in fibroblasts <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1855709&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1855709</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MISCELLANEOUS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Approximately 50% of cases are acute, severe neonatal illness often with rapid death and 50% are chronic episodic with asymptomatic intervals<br /> -
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Odor of 'sweaty feet'<br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MOLECULAR BASIS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Caused by mutation in the isovaleryl Co-A dehydrogenase gene (IVD, <a href="/entry/607036#0001">607036.0001</a>)<br />
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</span>
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</div>
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</div>
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</div>
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<div class="text-right">
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
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</div>
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</div>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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</span>
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</span>
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</h4>
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<div id="mimTextFold" class="collapse in ">
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because of evidence that isovaleric acidemia (IVA) is caused by homozygous or compound heterozygous mutation in the isovaleryl CoA dehydrogenase gene (IVD; <a href="/entry/607036">607036</a>) on chromosome 15q15.</p>
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</span>
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<div>
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<br />
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<div>
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<a id="description" class="mim-anchor"></a>
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>Isovaleric acidemia (IVA) is an inborn error of leucine metabolism caused by a deficiency of isovaleryl-CoA dehydrogenase. It can present with severe neonatal ketoacidosis leading to death, but in milder cases recurrent episodes of ketoacidosis of varying degree occur later in infancy and childhood (summary by <a href="#21" class="mim-tip-reference" title="Vockley, J., Parimoo, B., Tanaka, K. <strong>Molecular characterization of four different classes of mutations in the isovaleryl-CoA dehydrogenase gene responsible for isovaleric acidemia.</strong> Am. J. Hum. Genet. 49: 147-157, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2063866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2063866</a>]" pmid="2063866">Vockley et al., 1991</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2063866" 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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<div>
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<br />
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<div>
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<a id="clinicalFeatures" class="mim-anchor"></a>
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<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Clinical Features</strong>
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</span>
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</h4>
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</div>
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<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
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<span class="mim-text-font">
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<p>Two forms of isovaleric acidemia are recognized: the acute neonatal form, leading to massive metabolic acidosis from the first days of life and rapid death (e.g., <a href="#15" class="mim-tip-reference" title="Newman, C. G. H., Wilson, B. D. R., Callaghan, P., Young, L. <strong>Neonatal death associated with isovalericacidaemia.</strong> Lancet 290: 439-441, 1967. Note: Originally Volume II.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4166104/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4166104</a>] [<a href="https://doi.org/10.1016/s0140-6736(67)90854-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4166104">Newman et al., 1967</a>), and a chronic form in which periodic attacks of severe ketoacidosis occur with asymptomatic intervening periods (e.g., <a href="#18" class="mim-tip-reference" title="Tanaka, K., Budd, M. A., Efron, M. L., Isselbacher, K. J. <strong>Isovaleric acidemia: a new genetic defect of leucine metabolism.</strong> Proc. Nat. Acad. Sci. 56: 236-242, 1966.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5229850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5229850</a>] [<a href="https://doi.org/10.1073/pnas.56.1.236" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="5229850">Tanaka et al., 1966</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5229850+4166104" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Budd, M. A., Tanaka, K. R., Holmes, L. B., Efron, M. L., Crawford, J. D., Isselbacher, K. J. <strong>Isovaleric acidemia: clinical feature of a new genetic defect of leucine metabolism.</strong> New Eng. J. Med. 277: 321-327, 1967.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4378266/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4378266</a>] [<a href="https://doi.org/10.1056/NEJM196708172770701" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4378266">Budd et al. (1967)</a> observed brother and sister who, before the age of 6 months, showed retarded psychomotor development, a peculiar odor resembling sweaty feet, an aversion to dietary protein, and pernicious vomiting, leading to acidosis and coma. The unusual smell was identified as isovaleric acid, an intermediary of leucine, by experts of the Arthur D. Little Co., Industrial Consultants, Cambridge, Mass. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4378266" 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="Sidbury, J. B., Jr., Smith, E. K., Harlan, W. <strong>An inborn error of short-chain fatty acid metabolism: the odor-of-sweaty-feet syndrome.</strong> J. Pediat. 70: 8-15, 1967.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6016812/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6016812</a>] [<a href="https://doi.org/10.1016/s0022-3476(67)80160-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6016812">Sidbury et al. (1967)</a> observed that 3 of 4 children of a second-cousin marriage died in the first 2 weeks of life with the following symptoms after the first 3 days: convulsions, lethargy, dehydration, moderate hepatomegaly, depressed platelets and leukocytes, and an unusual urinary odor like that of sweaty feet. Postmortem examination showed mainly changes related to the hematologic findings: hypoplastic marrow, scattered hemorrhages of viscera, and terminal septicemia. The unusual odor was the result of butyric and hexanoic acids. They suggested that it is an inborn error of short-chain fatty acid metabolism and, more specifically, that a defect in green acyl dehydrogenase may be involved. In a second family a brother and sister with unrelated parents had a similar ailment. These cases are considered to have been instances of isovaleric acidemia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6016812" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Ando, T., Klingberg, W. G., Ward, A. N., Rasmussen, K., Nyhan, W. L. <strong>Isovaleric acidemia presenting with altered metabolism of glycine.</strong> Pediat. Res. 5: 478-486, 1971."None>Ando et al. (1971)</a> showed that isovaleric acidemia can produce hyperglycinemia and leukopenia, as well as episodic ketoacidosis, thus resembling propionic acidemia and methylmalonic acidemia.</p><p><a href="#11" class="mim-tip-reference" title="Gerdes, A.-M., Gregersen, N., Ludvigsson, P., Guttler, F. <strong>A Scandinavian case of isovaleric acidaemia.</strong> J. Inherit. Metab. Dis. 11: 219-220, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3139936/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3139936</a>] [<a href="https://doi.org/10.1007/BF01799879" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3139936">Gerdes et al. (1988)</a> described a patient with the chronic intermittent type of the disease, who was born to unrelated Icelandic parents. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3139936" 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="#20" class="mim-tip-reference" title="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://doi.org/10.1001/archneurol.2009.333" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20142522">Testai and Gorelick (2010)</a> noted that patients with branched-chain organic aciduria, including isovaleric aciduria, propionic aciduria (<a href="/entry/606054">606054</a>), and methylmalonic aciduria (<a href="/entry/251000">251000</a>), rarely have strokes. Cerebellar hemorrhage has been described in all 3 disorders, and basal ganglia ischemic stroke has been described in propionic aciduria and methylmalonic aciduria. These events may occur in the absence of metabolic decompensation. <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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<p><a href="#4" class="mim-tip-reference" title="Cohn, R. M., Yudkoff, R., Rothman, R., Segal, S. <strong>Isovaleric acidemia: use of glycine therapy in neonates.</strong> New Eng. J. Med. 299: 996-999, 1978.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/692626/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">692626</a>] [<a href="https://doi.org/10.1056/NEJM197811022991807" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="692626">Cohn et al. (1978)</a> demonstrated that administration of glycine reduces isovaleric acidemia in neonates by conjugating isovaleric acid, with urinary excretion of the conjugate. <a href="#14" class="mim-tip-reference" title="Naglak, M., Salvo, R., Madsen, K., Dembure, P., Elsas, L. <strong>The treatment of isovaleric acidemia with glycine supplement.</strong> Pediat. Res. 24: 9-13, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3137519/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3137519</a>] [<a href="https://doi.org/10.1203/00006450-198807000-00004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3137519">Naglak et al. (1988)</a> also demonstrated that, in addition to restriction of leucine intake, glycine supplementation can be useful in management. They suggested that clinical and biochemical measures should be used as guides to determine the amount of leucine that can be tolerated and the optimum glycine supplement for each patient. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=692626+3137519" 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>The phenotypic abnormalities in this disorder result from an accumulation of isovaleric acid, which is toxic to the central nervous system. An alternative pathway through glycine-N-acylase (<a href="https://enzyme.expasy.org/EC/2.3.1.13" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 2.3.1.13</a>) allows detoxification by producing isovalerylglycine, which is excreted.</p><p><a href="#16" class="mim-tip-reference" title="Rhead, W. J., Tanaka, K. <strong>Demonstration of a specific mitochondrial isovaleryl-CoA dehydrogenase deficiency in fibroblasts from patients with isovaleric acidemia.</strong> Proc. Nat. Acad. Sci. 77: 580-583, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6928646/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6928646</a>] [<a href="https://doi.org/10.1073/pnas.77.1.580" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6928646">Rhead and Tanaka (1980)</a> demonstrated a specific deficiency of mitochondrial isovaleryl-CoA dehydrogenase activity in skin fibroblasts from patients with IVA. Mitochondrial butyryl-CoA dehydrogenase activity was maintained at normal levels. Although clinical heterogeneity is observed, cell-fusion studies (<a href="#6" class="mim-tip-reference" title="Dubiel, B., Dabrowski, C., Wetts, R., Tanaka, K. <strong>Complementation studies of isovaleric acidemia and glutaric aciduria type II using cultured skin fibroblasts.</strong> J. Clin. Invest. 72: 1543-1552, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6630517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6630517</a>] [<a href="https://doi.org/10.1172/JCI111113" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6630517">Dubiel et al., 1983</a>) involving 12 cell lines, each from a different patient and representing a variety of clinical presentation, showed no complementation. Complementation was observed when IVA cells were fused with those from glutaric aciduria IIB (<a href="/entry/231680">231680</a>). The authors concluded that the same gene, coding for isovaleryl CoA dehydrogenase, was mutated in all cell lines. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6630517+6928646" 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="#21" class="mim-tip-reference" title="Vockley, J., Parimoo, B., Tanaka, K. <strong>Molecular characterization of four different classes of mutations in the isovaleryl-CoA dehydrogenase gene responsible for isovaleric acidemia.</strong> Am. J. Hum. Genet. 49: 147-157, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2063866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2063866</a>]" pmid="2063866">Vockley et al. (1991)</a> demonstrated with autosomal recessive inheritance of isovaleric acidemia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2063866" 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>Despite the findings from complementation studies indicating the involvement of a single IVD gene in this disorder (<a href="#6" class="mim-tip-reference" title="Dubiel, B., Dabrowski, C., Wetts, R., Tanaka, K. <strong>Complementation studies of isovaleric acidemia and glutaric aciduria type II using cultured skin fibroblasts.</strong> J. Clin. Invest. 72: 1543-1552, 1983.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6630517/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6630517</a>] [<a href="https://doi.org/10.1172/JCI111113" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="6630517">Dubiel et al., 1983</a>), analysis of the variant enzyme in 15 IVA fibroblast cell lines showed 5 distinct classes of variants which differed in subunit molecular size. <a href="#12" class="mim-tip-reference" title="Ikeda, Y., Keese, S. M., Tanaka, K. <strong>Molecular heterogeneity of variant isovaleryl-CoA dehydrogenase from cultured isovaleric acidemia fibroblasts.</strong> Proc. Nat. Acad. Sci. 82: 7081-7085, 1985.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3863140/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3863140</a>] [<a href="https://doi.org/10.1073/pnas.82.20.7081" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3863140">Ikeda et al. (1985)</a> suggested that these variants, in which residual enzyme activity was reduced to 0 to 3% of normal, were caused by point mutations or premature terminations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6630517+3863140" 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 patient with type I isovaleric acidemia, <a href="#21" class="mim-tip-reference" title="Vockley, J., Parimoo, B., Tanaka, K. <strong>Molecular characterization of four different classes of mutations in the isovaleryl-CoA dehydrogenase gene responsible for isovaleric acidemia.</strong> Am. J. Hum. Genet. 49: 147-157, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2063866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2063866</a>]" pmid="2063866">Vockley et al. (1991)</a> demonstrated a homozygous change of thymine-125 to cytosine in the IVD gene, which was predicted to cause a substitution of proline for leucine at position 13 of the mature IVD protein (L13P; <a href="/entry/607036#0001">607036.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2063866" 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>Since the implementation of newborn screening by tandem mass spectrometry in many states and countries, presymptomatic diagnosis of isovaleric acidemia has been possible. Molecular genetic analysis of the IVD gene in 19 subjects whose condition was detected through newborn screening led to the identification of 1 recurring mutation, 932C-T (A282V; <a href="/entry/607036#0007">607036.0007</a>), in 47% of mutant alleles (<a href="#9" class="mim-tip-reference" title="Ensenauer, R., Vockley, J., Willard, J.-M., Huey, J. C., Sass, J. O., Edland, S. D., Burton, B. K., Berry, S. A., Santer, R., Grunert, S., Koch, H.-G., Marquardt, I., Rinaldo, P., Hahn, S., Matern, D. <strong>A common mutation is associated with a mild, potentially asymptomatic phenotype in patients with isovaleric acidemia diagnosed by newborn screening.</strong> Am. J. Hum. Genet. 75: 1136-1142, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15486829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15486829</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15486829[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/426318" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15486829">Ensenauer et al., 2004</a>). Surprisingly, family studies identified 6 healthy older sibs with identical genotype and biochemical evidence of isovaleric acidemia. The findings indicated the frequent occurrence of a novel mild and potentially asymptomatic phenotype of IVA. This has significant consequences for patient management and counseling. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15486829" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#Ando1973" class="mim-tip-reference" title="Ando, T., Nyhan, W. L., Bachmann, C., Rasmussen, K., Scott, R., Smith, E. K. <strong>Isovaleric acidemia: identification of isovalerylglycine, and 3-hydroxyisovalerate in urine of a patient previously reported as having butyric and hexanoic acidemia.</strong> J. Pediat. 82: 243-248, 1973.">Ando et al. (1973)</a>; <a href="#de1986" class="mim-tip-reference" title="de Sousa, C., Chalmers, R. A., Stacey, T. E., Tracey, B. M., Weaver, C. M., Bradley, D. <strong>The response to L-carnitine and glycine therapy in isovaleric acidaemia.</strong> Europ. J. Pediat. 144: 451-456, 1986.">de Sousa et al. (1986)</a>; <a href="#Duran1979" class="mim-tip-reference" title="Duran, M., van Sprang, F. J., Drewes, J. G., Bruinvis, L., Ketting, D., Wadman, S. K. <strong>Two sisters with isovaleric acidemia, multiple attacks of ketoacidosis and normal development.</strong> Europ. J. Pediat. 131: 205-211, 1979.">Duran et al. (1979)</a>; <a href="#Efron1967" class="mim-tip-reference" title="Efron, M. L. <strong>Isovaleric acidemia.</strong> Am. J. Dis. Child. 113: 74-76, 1967.">Efron (1967)</a>; <a href="#Fischer1981" class="mim-tip-reference" title="Fischer, A. Q., Challa, V. R., Burton, B. K., McLean, W. T. <strong>Cerebellar hemorrhage complicating isovaleric acidemia: a case report.</strong> Neurology 31: 746-748, 1981.">Fischer et al. (1981)</a>; <a href="#Kelleher1980" class="mim-tip-reference" title="Kelleher, J. F., Jr., Yudkoff, M., Hutchinson, R., August, C. S., Cohn, R. M. <strong>The pancytopenia of isovaleric acidemia.</strong> Pediatrics 65: 1023-1027, 1980.">Kelleher et al. (1980)</a>; <a href="#Tanaka1968" class="mim-tip-reference" title="Tanaka, K., Orr, J., Isselbacher, K. J. <strong>Identification of b-hydroxyisovaleric acid in the urine of a patient with isovaleric acidemia.</strong> Biochim. Biophys. Acta 152: 638-641, 1968.">Tanaka
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et al. (1968)</a>
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<span class="mim-font">
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<span id="mimReferencesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>REFERENCES</strong>
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</h4>
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Ando, T., Nyhan, W. L., Bachmann, C., Rasmussen, K., Scott, R., Smith, E. K.
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<strong>Isovaleric acidemia: identification of isovalerylglycine, and 3-hydroxyisovalerate in urine of a patient previously reported as having butyric and hexanoic acidemia.</strong>
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[<a href="https://doi.org/10.1016/s0022-3476(73)80161-1" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1056/NEJM196708172770701" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1056/NEJM197811022991807" target="_blank">Full Text</a>]
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de Sousa, C., Chalmers, R. A., Stacey, T. E., Tracey, B. M., Weaver, C. M., Bradley, D.
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<strong>The response to L-carnitine and glycine therapy in isovaleric acidaemia.</strong>
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[<a href="https://doi.org/10.1007/BF00441737" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1172/JCI111113" target="_blank">Full Text</a>]
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<a id="Duran1979" class="mim-anchor"></a>
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<div class="">
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Duran, M., van Sprang, F. J., Drewes, J. G., Bruinvis, L., Ketting, D., Wadman, S. K.
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<strong>Two sisters with isovaleric acidemia, multiple attacks of ketoacidosis and normal development.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/477679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">477679</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=477679" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/BF00538944" target="_blank">Full Text</a>]
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Am. J. Dis. Child. 113: 74-76, 1967.
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[<a href="https://doi.org/10.1001/archpedi.1967.02090160124015" target="_blank">Full Text</a>]
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<a id="Ensenauer2004" class="mim-anchor"></a>
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Ensenauer, R., Vockley, J., Willard, J.-M., Huey, J. C., Sass, J. O., Edland, S. D., Burton, B. K., Berry, S. A., Santer, R., Grunert, S., Koch, H.-G., Marquardt, I., Rinaldo, P., Hahn, S., Matern, D.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15486829/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15486829</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15486829[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=15486829" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/426318" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1212/wnl.31.6.746" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF01799879" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1073/pnas.82.20.7081" target="_blank">Full Text</a>]
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<a id="13" class="mim-anchor"></a>
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<a id="Kelleher1980" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Kelleher, J. F., Jr., Yudkoff, M., Hutchinson, R., August, C. S., Cohn, R. M.
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<strong>The pancytopenia of isovaleric acidemia.</strong>
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Pediatrics 65: 1023-1027, 1980.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7367115/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7367115</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7367115" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="14" class="mim-anchor"></a>
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<a id="Naglak1988" class="mim-anchor"></a>
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<strong>The treatment of isovaleric acidemia with glycine supplement.</strong>
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[<a href="https://doi.org/10.1203/00006450-198807000-00004" target="_blank">Full Text</a>]
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Newman, C. G. H., Wilson, B. D. R., Callaghan, P., Young, L.
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[<a href="https://doi.org/10.1016/s0140-6736(67)90854-9" target="_blank">Full Text</a>]
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<a id="Rhead1980" class="mim-anchor"></a>
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Rhead, W. J., Tanaka, K.
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<strong>Demonstration of a specific mitochondrial isovaleryl-CoA dehydrogenase deficiency in fibroblasts from patients with isovaleric acidemia.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6928646/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6928646</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6928646" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.77.1.580" target="_blank">Full Text</a>]
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</p>
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<a id="17" class="mim-anchor"></a>
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<a id="Sidbury1967" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sidbury, J. B., Jr., Smith, E. K., Harlan, W.
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<strong>An inborn error of short-chain fatty acid metabolism: the odor-of-sweaty-feet syndrome.</strong>
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J. Pediat. 70: 8-15, 1967.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6016812/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6016812</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6016812" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0022-3476(67)80160-4" target="_blank">Full Text</a>]
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</p>
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</div>
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<a id="18" class="mim-anchor"></a>
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<a id="Tanaka1966" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tanaka, K., Budd, M. A., Efron, M. L., Isselbacher, K. J.
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<strong>Isovaleric acidemia: a new genetic defect of leucine metabolism.</strong>
|
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Proc. Nat. Acad. Sci. 56: 236-242, 1966.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5229850/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5229850</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5229850" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1073/pnas.56.1.236" target="_blank">Full Text</a>]
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<a id="19" class="mim-anchor"></a>
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<a id="Tanaka1968" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Tanaka, K., Orr, J., Isselbacher, K. J.
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<strong>Identification of b-hydroxyisovaleric acid in the urine of a patient with isovaleric acidemia.</strong>
|
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Biochim. Biophys. Acta 152: 638-641, 1968.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5656832/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5656832</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5656832" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0005-2760(68)90107-0" target="_blank">Full Text</a>]
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</p>
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</div>
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<a id="20" class="mim-anchor"></a>
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<a id="Testai2010" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Testai, F. D., Gorelick, P. B.
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<strong>Inherited metabolic disorders and stroke part 2: homocystinuria, organic acidurias, and urea cycle disorders.</strong>
|
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Arch. Neurol. 67: 148-153, 2010.
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[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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[<a href="https://doi.org/10.1001/archneurol.2009.333" target="_blank">Full Text</a>]
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<a id="21" class="mim-anchor"></a>
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<a id="Vockley1991" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Vockley, J., Parimoo, B., Tanaka, K.
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<strong>Molecular characterization of four different classes of mutations in the isovaleryl-CoA dehydrogenase gene responsible for isovaleric acidemia.</strong>
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Am. J. Hum. Genet. 49: 147-157, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2063866/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2063866</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2063866" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<br />
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 10/11/2010
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<div class="row collapse" id="mimCollapseContributors">
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<span class="mim-text-font">
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Victor A. McKusick - updated : 11/12/2004<br>Cassandra L. Kniffin - updated : 7/2/2002<br>Victor A. McKusick - updated : 3/31/2000
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</span>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 6/3/1986
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</span>
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<a id="editHistory" class="mim-anchor"></a>
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<span class="text-nowrap mim-text-font">
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 05/13/2024
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<div class="row collapse" id="mimCollapseEditHistory">
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<div class="col-lg-offset-2 col-md-offset-2 col-sm-offset-4 col-xs-offset-4 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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carol : 09/08/2023<br>carol : 06/08/2016<br>carol : 11/15/2010<br>wwang : 10/29/2010<br>ckniffin : 10/11/2010<br>terry : 3/5/2009<br>terry : 6/9/2005<br>terry : 4/20/2005<br>terry : 4/6/2005<br>carol : 12/9/2004<br>alopez : 11/18/2004<br>terry : 11/12/2004<br>carol : 7/2/2002<br>ckniffin : 7/2/2002<br>ckniffin : 6/27/2002<br>ckniffin : 6/13/2002<br>mgross : 4/10/2000<br>terry : 3/31/2000<br>carol : 6/19/1998<br>terry : 6/4/1998<br>davew : 8/19/1994<br>carol : 5/10/1994<br>terry : 5/9/1994<br>mimadm : 2/19/1994<br>carol : 1/4/1993<br>supermim : 3/16/1992
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<h3>
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<span class="mim-font">
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<strong>#</strong> 243500
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</span>
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</h3>
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<div>
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<h3>
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<span class="mim-font">
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ISOVALERIC ACIDEMIA; IVA
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</div>
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<div>
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<br />
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<div>
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<h4>
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<span class="mim-font">
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ISOVALERIC ACID CoA DEHYDROGENASE DEFICIENCY<br />
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IVD DEFICIENCY
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</span>
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</h4>
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<div>
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<br />
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 87827003;
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<strong>ICD10CM:</strong> E71.110;
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<strong>ORPHA:</strong> 33;
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<strong>DO:</strong> 14753;
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</span>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Phenotype-Gene Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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</thead>
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
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15q15.1
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</span>
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</td>
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<td>
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<span class="mim-font">
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Isovaleric acidemia
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</span>
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</td>
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<td>
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<span class="mim-font">
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243500
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</span>
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</td>
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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<td>
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<span class="mim-font">
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IVD
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</span>
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</td>
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<td>
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<span class="mim-font">
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607036
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<h4>
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because of evidence that isovaleric acidemia (IVA) is caused by homozygous or compound heterozygous mutation in the isovaleryl CoA dehydrogenase gene (IVD; 607036) on chromosome 15q15.</p>
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</span>
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<div>
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<br />
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<div>
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<h4>
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<span class="mim-font">
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<strong>Description</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Isovaleric acidemia (IVA) is an inborn error of leucine metabolism caused by a deficiency of isovaleryl-CoA dehydrogenase. It can present with severe neonatal ketoacidosis leading to death, but in milder cases recurrent episodes of ketoacidosis of varying degree occur later in infancy and childhood (summary by Vockley et al., 1991). </p>
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</span>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Clinical Features</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>Two forms of isovaleric acidemia are recognized: the acute neonatal form, leading to massive metabolic acidosis from the first days of life and rapid death (e.g., Newman et al., 1967), and a chronic form in which periodic attacks of severe ketoacidosis occur with asymptomatic intervening periods (e.g., Tanaka et al., 1966). </p><p>Budd et al. (1967) observed brother and sister who, before the age of 6 months, showed retarded psychomotor development, a peculiar odor resembling sweaty feet, an aversion to dietary protein, and pernicious vomiting, leading to acidosis and coma. The unusual smell was identified as isovaleric acid, an intermediary of leucine, by experts of the Arthur D. Little Co., Industrial Consultants, Cambridge, Mass. </p><p>Sidbury et al. (1967) observed that 3 of 4 children of a second-cousin marriage died in the first 2 weeks of life with the following symptoms after the first 3 days: convulsions, lethargy, dehydration, moderate hepatomegaly, depressed platelets and leukocytes, and an unusual urinary odor like that of sweaty feet. Postmortem examination showed mainly changes related to the hematologic findings: hypoplastic marrow, scattered hemorrhages of viscera, and terminal septicemia. The unusual odor was the result of butyric and hexanoic acids. They suggested that it is an inborn error of short-chain fatty acid metabolism and, more specifically, that a defect in green acyl dehydrogenase may be involved. In a second family a brother and sister with unrelated parents had a similar ailment. These cases are considered to have been instances of isovaleric acidemia. </p><p>Ando et al. (1971) showed that isovaleric acidemia can produce hyperglycinemia and leukopenia, as well as episodic ketoacidosis, thus resembling propionic acidemia and methylmalonic acidemia.</p><p>Gerdes et al. (1988) described a patient with the chronic intermittent type of the disease, who was born to unrelated Icelandic parents. </p><p>In a review of inherited metabolic disorders and stroke, Testai and Gorelick (2010) noted that patients with branched-chain organic aciduria, including isovaleric aciduria, propionic aciduria (606054), and methylmalonic aciduria (251000), rarely have strokes. Cerebellar hemorrhage has been described in all 3 disorders, and basal ganglia ischemic stroke has been described in propionic aciduria and methylmalonic aciduria. These events may occur in the absence of metabolic decompensation. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Clinical Management</strong>
|
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</span>
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</h4>
|
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</div>
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<span class="mim-text-font">
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|
<p>Cohn et al. (1978) demonstrated that administration of glycine reduces isovaleric acidemia in neonates by conjugating isovaleric acid, with urinary excretion of the conjugate. Naglak et al. (1988) also demonstrated that, in addition to restriction of leucine intake, glycine supplementation can be useful in management. They suggested that clinical and biochemical measures should be used as guides to determine the amount of leucine that can be tolerated and the optimum glycine supplement for each patient. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>Pathogenesis</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>The phenotypic abnormalities in this disorder result from an accumulation of isovaleric acid, which is toxic to the central nervous system. An alternative pathway through glycine-N-acylase (EC 2.3.1.13) allows detoxification by producing isovalerylglycine, which is excreted.</p><p>Rhead and Tanaka (1980) demonstrated a specific deficiency of mitochondrial isovaleryl-CoA dehydrogenase activity in skin fibroblasts from patients with IVA. Mitochondrial butyryl-CoA dehydrogenase activity was maintained at normal levels. Although clinical heterogeneity is observed, cell-fusion studies (Dubiel et al., 1983) involving 12 cell lines, each from a different patient and representing a variety of clinical presentation, showed no complementation. Complementation was observed when IVA cells were fused with those from glutaric aciduria IIB (231680). The authors concluded that the same gene, coding for isovaleryl CoA dehydrogenase, was mutated in all cell lines. </p>
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<strong>Inheritance</strong>
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<span class="mim-text-font">
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<p>Vockley et al. (1991) demonstrated with autosomal recessive inheritance of isovaleric acidemia. </p>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<p>Despite the findings from complementation studies indicating the involvement of a single IVD gene in this disorder (Dubiel et al., 1983), analysis of the variant enzyme in 15 IVA fibroblast cell lines showed 5 distinct classes of variants which differed in subunit molecular size. Ikeda et al. (1985) suggested that these variants, in which residual enzyme activity was reduced to 0 to 3% of normal, were caused by point mutations or premature terminations. </p><p>In a patient with type I isovaleric acidemia, Vockley et al. (1991) demonstrated a homozygous change of thymine-125 to cytosine in the IVD gene, which was predicted to cause a substitution of proline for leucine at position 13 of the mature IVD protein (L13P; 607036.0001). </p><p>Since the implementation of newborn screening by tandem mass spectrometry in many states and countries, presymptomatic diagnosis of isovaleric acidemia has been possible. Molecular genetic analysis of the IVD gene in 19 subjects whose condition was detected through newborn screening led to the identification of 1 recurring mutation, 932C-T (A282V; 607036.0007), in 47% of mutant alleles (Ensenauer et al., 2004). Surprisingly, family studies identified 6 healthy older sibs with identical genotype and biochemical evidence of isovaleric acidemia. The findings indicated the frequent occurrence of a novel mild and potentially asymptomatic phenotype of IVA. This has significant consequences for patient management and counseling. </p>
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<h4>
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<span class="mim-font">
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<strong>See Also:</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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Ando et al. (1973); de Sousa et al. (1986); Duran et al. (1979);
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Efron (1967); Fischer et al. (1981); Kelleher et al. (1980); Tanaka
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et al. (1968)
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</span>
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<div>
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<br />
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<p class="mim-text-font">
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Ando, T., Klingberg, W. G., Ward, A. N., Rasmussen, K., Nyhan, W. L.
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<strong>Isovaleric acidemia presenting with altered metabolism of glycine.</strong>
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Pediat. Res. 5: 478-486, 1971.
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Ando, T., Nyhan, W. L., Bachmann, C., Rasmussen, K., Scott, R., Smith, E. K.
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<strong>Isovaleric acidemia: identification of isovalerylglycine, and 3-hydroxyisovalerate in urine of a patient previously reported as having butyric and hexanoic acidemia.</strong>
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J. Pediat. 82: 243-248, 1973.
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[PubMed: 4684367]
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[Full Text: https://doi.org/10.1016/s0022-3476(73)80161-1]
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<p class="mim-text-font">
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Budd, M. A., Tanaka, K. R., Holmes, L. B., Efron, M. L., Crawford, J. D., Isselbacher, K. J.
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<strong>Isovaleric acidemia: clinical feature of a new genetic defect of leucine metabolism.</strong>
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New Eng. J. Med. 277: 321-327, 1967.
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[PubMed: 4378266]
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[Full Text: https://doi.org/10.1056/NEJM196708172770701]
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</p>
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<p class="mim-text-font">
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Cohn, R. M., Yudkoff, R., Rothman, R., Segal, S.
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<strong>Isovaleric acidemia: use of glycine therapy in neonates.</strong>
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New Eng. J. Med. 299: 996-999, 1978.
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[PubMed: 692626]
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[Full Text: https://doi.org/10.1056/NEJM197811022991807]
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</li>
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<li>
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<p class="mim-text-font">
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de Sousa, C., Chalmers, R. A., Stacey, T. E., Tracey, B. M., Weaver, C. M., Bradley, D.
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<strong>The response to L-carnitine and glycine therapy in isovaleric acidaemia.</strong>
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Europ. J. Pediat. 144: 451-456, 1986.
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[PubMed: 3956533]
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[Full Text: https://doi.org/10.1007/BF00441737]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Dubiel, B., Dabrowski, C., Wetts, R., Tanaka, K.
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<strong>Complementation studies of isovaleric acidemia and glutaric aciduria type II using cultured skin fibroblasts.</strong>
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J. Clin. Invest. 72: 1543-1552, 1983.
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[PubMed: 6630517]
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[Full Text: https://doi.org/10.1172/JCI111113]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Duran, M., van Sprang, F. J., Drewes, J. G., Bruinvis, L., Ketting, D., Wadman, S. K.
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<strong>Two sisters with isovaleric acidemia, multiple attacks of ketoacidosis and normal development.</strong>
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Europ. J. Pediat. 131: 205-211, 1979.
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[PubMed: 477679]
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[Full Text: https://doi.org/10.1007/BF00538944]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Efron, M. L.
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<strong>Isovaleric acidemia.</strong>
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Am. J. Dis. Child. 113: 74-76, 1967.
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[PubMed: 6015910]
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[Full Text: https://doi.org/10.1001/archpedi.1967.02090160124015]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Ensenauer, R., Vockley, J., Willard, J.-M., Huey, J. C., Sass, J. O., Edland, S. D., Burton, B. K., Berry, S. A., Santer, R., Grunert, S., Koch, H.-G., Marquardt, I., Rinaldo, P., Hahn, S., Matern, D.
|
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<strong>A common mutation is associated with a mild, potentially asymptomatic phenotype in patients with isovaleric acidemia diagnosed by newborn screening.</strong>
|
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Am. J. Hum. Genet. 75: 1136-1142, 2004.
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[PubMed: 15486829]
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[Full Text: https://doi.org/10.1086/426318]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Fischer, A. Q., Challa, V. R., Burton, B. K., McLean, W. T.
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<strong>Cerebellar hemorrhage complicating isovaleric acidemia: a case report.</strong>
|
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Neurology 31: 746-748, 1981.
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[PubMed: 7195490]
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[Full Text: https://doi.org/10.1212/wnl.31.6.746]
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</p>
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</li>
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<p class="mim-text-font">
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Gerdes, A.-M., Gregersen, N., Ludvigsson, P., Guttler, F.
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<strong>A Scandinavian case of isovaleric acidaemia.</strong>
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J. Inherit. Metab. Dis. 11: 219-220, 1988.
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[PubMed: 3139936]
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[Full Text: https://doi.org/10.1007/BF01799879]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Ikeda, Y., Keese, S. M., Tanaka, K.
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<strong>Molecular heterogeneity of variant isovaleryl-CoA dehydrogenase from cultured isovaleric acidemia fibroblasts.</strong>
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Proc. Nat. Acad. Sci. 82: 7081-7085, 1985.
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[PubMed: 3863140]
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[Full Text: https://doi.org/10.1073/pnas.82.20.7081]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Kelleher, J. F., Jr., Yudkoff, M., Hutchinson, R., August, C. S., Cohn, R. M.
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<strong>The pancytopenia of isovaleric acidemia.</strong>
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Pediatrics 65: 1023-1027, 1980.
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[PubMed: 7367115]
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<p class="mim-text-font">
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Naglak, M., Salvo, R., Madsen, K., Dembure, P., Elsas, L.
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<strong>The treatment of isovaleric acidemia with glycine supplement.</strong>
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Pediat. Res. 24: 9-13, 1988.
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[PubMed: 3137519]
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[Full Text: https://doi.org/10.1203/00006450-198807000-00004]
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<p class="mim-text-font">
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Newman, C. G. H., Wilson, B. D. R., Callaghan, P., Young, L.
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<strong>Neonatal death associated with isovalericacidaemia.</strong>
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Lancet 290: 439-441, 1967. Note: Originally Volume II.
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[PubMed: 4166104]
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[Full Text: https://doi.org/10.1016/s0140-6736(67)90854-9]
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<p class="mim-text-font">
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Rhead, W. J., Tanaka, K.
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<strong>Demonstration of a specific mitochondrial isovaleryl-CoA dehydrogenase deficiency in fibroblasts from patients with isovaleric acidemia.</strong>
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Proc. Nat. Acad. Sci. 77: 580-583, 1980.
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[PubMed: 6928646]
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[Full Text: https://doi.org/10.1073/pnas.77.1.580]
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<p class="mim-text-font">
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Sidbury, J. B., Jr., Smith, E. K., Harlan, W.
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<strong>An inborn error of short-chain fatty acid metabolism: the odor-of-sweaty-feet syndrome.</strong>
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J. Pediat. 70: 8-15, 1967.
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[PubMed: 6016812]
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<p class="mim-text-font">
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Tanaka, K., Budd, M. A., Efron, M. L., Isselbacher, K. J.
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<strong>Isovaleric acidemia: a new genetic defect of leucine metabolism.</strong>
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Proc. Nat. Acad. Sci. 56: 236-242, 1966.
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[PubMed: 5229850]
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[Full Text: https://doi.org/10.1073/pnas.56.1.236]
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<p class="mim-text-font">
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Tanaka, K., Orr, J., Isselbacher, K. J.
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<strong>Identification of b-hydroxyisovaleric acid in the urine of a patient with isovaleric acidemia.</strong>
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Biochim. Biophys. Acta 152: 638-641, 1968.
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[PubMed: 5656832]
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[Full Text: https://doi.org/10.1016/0005-2760(68)90107-0]
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<p class="mim-text-font">
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Testai, F. D., Gorelick, P. B.
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<strong>Inherited metabolic disorders and stroke part 2: homocystinuria, organic acidurias, and urea cycle disorders.</strong>
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[Full Text: https://doi.org/10.1001/archneurol.2009.333]
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<li>
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<p class="mim-text-font">
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Vockley, J., Parimoo, B., Tanaka, K.
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<strong>Molecular characterization of four different classes of mutations in the isovaleryl-CoA dehydrogenase gene responsible for isovaleric acidemia.</strong>
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Am. J. Hum. Genet. 49: 147-157, 1991.
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[PubMed: 2063866]
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 10/11/2010<br>Victor A. McKusick - updated : 11/12/2004<br>Cassandra L. Kniffin - updated : 7/2/2002<br>Victor A. McKusick - updated : 3/31/2000
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<span class="mim-text-font">
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Victor A. McKusick : 6/3/1986
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carol : 05/13/2024<br>carol : 09/08/2023<br>carol : 06/08/2016<br>carol : 11/15/2010<br>wwang : 10/29/2010<br>ckniffin : 10/11/2010<br>terry : 3/5/2009<br>terry : 6/9/2005<br>terry : 4/20/2005<br>terry : 4/6/2005<br>carol : 12/9/2004<br>alopez : 11/18/2004<br>terry : 11/12/2004<br>carol : 7/2/2002<br>ckniffin : 7/2/2002<br>ckniffin : 6/27/2002<br>ckniffin : 6/13/2002<br>mgross : 4/10/2000<br>terry : 3/31/2000<br>carol : 6/19/1998<br>terry : 6/4/1998<br>davew : 8/19/1994<br>carol : 5/10/1994<br>terry : 5/9/1994<br>mimadm : 2/19/1994<br>carol : 1/4/1993<br>supermim : 3/16/1992
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