4612 lines
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- *600890 - HYDROXYACYL-CoA DEHYDROGENASE/3-KETOACYL-CoA THIOLASE/ENOYL-CoA HYDRATASE, ALPHA SUBUNIT; HADHA
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<div id="mimFloatingTocMenu" class="small" role="navigation">
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<p>
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<span class="h4">*600890</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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<nav>
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<a href="#title"><strong>Title</strong></a>
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<a href="#geneMap"><strong>Gene-Phenotype Relationships</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#description">Description</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#cloning">Cloning and Expression</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#geneStructure">Gene Structure</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#allelicVariants"><strong>Allelic Variants</strong></a>
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</li>
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<li role="presentation" style="margin-left: 1em">
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<a href="/allelicVariants/600890">Table View</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>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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</li>
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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>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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</nav>
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</div>
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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 id="mimFloatingLinksMenu">
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<div class="panel panel-primary" style="margin-bottom: 0px; border-radius: 4px 4px 0px 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimExternalLinks">
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<h4 class="panel-title">
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<a href="#mimExternalLinksFold" id="mimExternalLinksToggle" class="mimTriangleToggle" role="button" data-toggle="collapse">
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<div style="display: table-row">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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</div>
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<div id="mimExternalLinksFold" class="collapse in">
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<div class="panel-group" id="mimExternalLinksAccordion" role="tablist" aria-multiselectable="true">
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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="mimGenome">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGenomeLinksFold" id="mimGenomeLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimGenomeLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Genome
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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="mimGenomeLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel" aria-labelledby="genome">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ensembl.org/Homo_sapiens/Location/View?db=core;g=ENSG00000084754;t=ENST00000380649" class="mim-tip-hint" title="Genome databases for vertebrates and other eukaryotic species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/genome/gdv/browser/gene/?id=3030" class="mim-tip-hint" title="Detailed views of the complete genomes of selected organisms from vertebrates to protozoa." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Genome Viewer', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Genome Viewer</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=600890" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</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="mimDna">
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<span class="panel-title">
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<span class="small">
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<a href="#mimDnaLinksFold" id="mimDnaLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimDnaLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> DNA
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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="mimDnaLinksFold" 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.ensembl.org/Homo_sapiens/Transcript/Sequence_cDNA?db=core;g=ENSG00000084754;t=ENST00000380649" class="mim-tip-hint" title="Transcript-based views for coding and noncoding DNA." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl (MANE Select)</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000182" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/nuccore/NM_000182" class="mim-tip-hint" title="A collection of genome, gene, and transcript sequence data from several sources, including GenBank, RefSeq." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI RefSeq (MANE)', 'domain': 'ncbi.nlm.nih'})">NCBI RefSeq (MANE Select)</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&hgFind=omimGeneAcc&position=600890" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">UCSC Genome Browser</a></div>
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</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="mimProtein">
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<span class="panel-title">
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<span class="small">
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<a href="#mimProteinLinksFold" id="mimProteinLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
|
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<span id="mimProteinLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Protein
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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="mimProteinLinksFold" 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://hprd.org/summary?hprd_id=02934&isoform_id=02934_1&isoform_name=Isoform_1" class="mim-tip-hint" title="The Human Protein Reference Database; manually extracted and visually depicted information on human proteins." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HPRD', 'domain': 'hprd.org'})">HPRD</a></div>
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<div><a href="https://www.proteinatlas.org/search/HADHA" class="mim-tip-hint" title="The Human Protein Atlas contains information for a large majority of all human protein-coding genes regarding the expression and localization of the corresponding proteins based on both RNA and protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HumanProteinAtlas', 'domain': 'proteinatlas.org'})">Human Protein Atlas</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/protein/595267,862457,4587371,14328041,20127408,20141376,62702215,62822074,119621108,119621109,189053609,194373621,194380074,194387750,317040156" class="mim-tip-hint" title="NCBI protein data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Protein', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Protein</a></div>
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<div><a href="https://www.uniprot.org/uniprotkb/P40939" class="mim-tip-hint" title="Comprehensive protein sequence and functional information, including supporting data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UniProt', 'domain': 'uniprot.org'})">UniProt</a></div>
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</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="mimGeneInfo">
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<span class="panel-title">
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<span class="small">
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<a href="#mimGeneInfoLinksFold" id="mimGeneInfoLinksToggle" 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="mimGeneInfoLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Gene Info</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="mimGeneInfoLinksFold" 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="http://biogps.org/#goto=genereport&id=3030" class="mim-tip-hint" title="The Gene Portal Hub; customizable portal of gene and protein function information." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'BioGPS', 'domain': 'biogps.org'})">BioGPS</a></div>
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<div><a href="https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000084754;t=ENST00000380649" class="mim-tip-hint" title="Orthologs, paralogs, regulatory regions, and splice variants." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Ensembl', 'domain': 'ensembl.org'})">Ensembl</a></div>
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<div><a href="https://www.genecards.org/cgi-bin/carddisp.pl?gene=HADHA" class="mim-tip-hint" title="The Human Genome Compendium; web-based cards integrating automatically mined information on human genes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneCards', 'domain': 'genecards.org'})">GeneCards</a></div>
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<div><a href="http://amigo.geneontology.org/amigo/search/annotation?q=HADHA" class="mim-tip-hint" title="Terms, defined using controlled vocabulary, representing gene product properties (biologic process, cellular component, molecular function) across species." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GeneOntology', 'domain': 'amigo.geneontology.org'})">Gene Ontology</a></div>
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<div><a href="https://www.genome.jp/dbget-bin/www_bget?hsa+3030" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<dd><a href="http://v1.marrvel.org/search/gene/HADHA" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></dd>
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<dd><a href="https://monarchinitiative.org/NCBIGene:3030" class="mim-tip-hint" title="Monarch Initiative." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Monarch', 'domain': 'monarchinitiative.org'})">Monarch</a></dd>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/3030" class="mim-tip-hint" title="Gene-specific map, sequence, expression, structure, function, citation, and homology data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Gene', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Gene</a></div>
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<div><a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_chrom=chr2&hgg_gene=ENST00000380649.8&hgg_start=26190635&hgg_end=26244632&hgg_type=knownGene" class="mim-tip-hint" title="UCSC Genome Bioinformatics; gene-specific structure and function information with links to other databases." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC', 'domain': 'genome.ucsc.edu'})">UCSC</a></div>
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</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="mimClinicalResources">
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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="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="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse 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://search.clinicalgenome.org/kb/genes/HGNC:4801" class="mim-tip-hint" title="A ClinGen curated resource of ratings for the strength of evidence supporting or refuting the clinical validity of the claim(s) that variation in a particular gene causes disease." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinGen Validity', 'domain': 'search.clinicalgenome.org'})">ClinGen Validity</a></div>
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<div><a href="https://medlineplus.gov/genetics/gene/hadha" 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=600890[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>
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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="mimVariation">
|
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<span class="panel-title">
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<span class="small">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">▼</span> Variation
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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="mimVariationLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.ncbi.nlm.nih.gov/clinvar?term=600890[MIM]" class="mim-tip-hint" title="ClinVar aggregates information about sequence variation and its relationship to human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">ClinVar</a></div>
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<div><a href="https://gnomad.broadinstitute.org/gene/ENSG00000084754" class="mim-tip-hint" title="The Genome Aggregation Database (gnomAD), Broad Institute." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'gnomAD', 'domain': 'gnomad.broadinstitute.org'})">gnomAD</a></div>
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<div><a href="https://www.ebi.ac.uk/gwas/search?query=HADHA" class="mim-tip-hint" title="GWAS Catalog; NHGRI-EBI Catalog of published genome-wide association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Catalog', 'domain': 'gwascatalog.org'})">GWAS Catalog </a></div>
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<div><a href="https://www.gwascentral.org/search?q=HADHA" class="mim-tip-hint" title="GWAS Central; summary level genotype-to-phenotype information from genetic association studies." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GWAS Central', 'domain': 'gwascentral.org'})">GWAS Central </a></div>
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<div><a href="http://www.hgmd.cf.ac.uk/ac/gene.php?gene=HADHA" class="mim-tip-hint" title="Human Gene Mutation Database; published mutations causing or associated with human inherited disease; disease-associated/functional polymorphisms." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGMD', 'domain': 'hgmd.cf.ac.uk'})">HGMD</a></div>
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<div><a href="https://evs.gs.washington.edu/EVS/PopStatsServlet?searchBy=Gene+Hugo&target=HADHA&upstreamSize=0&downstreamSize=0&x=0&y=0" class="mim-tip-hint" title="National Heart, Lung, and Blood Institute Exome Variant Server." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NHLBI EVS', 'domain': 'evs.gs.washington.edu'})">NHLBI EVS</a></div>
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<div><a href="https://www.pharmgkb.org/gene/PA29175" class="mim-tip-hint" title="Pharmacogenomics Knowledge Base; curated and annotated information regarding the effects of human genetic variations on drug response." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PharmGKB', 'domain': 'pharmgkb.org'})">PharmGKB</a></div>
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</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/gene/HGNC:4801" 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="https://flybase.org/reports/FBgn0028479.html" class="mim-tip-hint" title="A Database of Drosophila Genes and Genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'FlyBase', 'domain': 'flybase.org'})">FlyBase</a></div>
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<div><a href="https://www.mousephenotype.org/data/genes/MGI:2135593" class="mim-tip-hint" title="International Mouse Phenotyping Consortium." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'IMPC', 'domain': 'knockoutmouse.org'})">IMPC</a></div>
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<div><a href="http://v1.marrvel.org/search/gene/HADHA#HomologGenesPanel" class="mim-tip-hint" title="Model organism Aggregated Resources for Rare Variant ExpLoration." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MARRVEL', 'domain': 'marrvel.org'})">MARRVEL</a></div>
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<div><a href="http://www.informatics.jax.org/marker/MGI:2135593" class="mim-tip-hint" title="Mouse Genome Informatics; international database resource for the laboratory mouse, including integrated genetic, genomic, and biological data." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Gene', 'domain': 'informatics.jax.org'})">MGI Mouse Gene</a></div>
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<div><a href="https://www.mmrrc.org/catalog/StrainCatalogSearchForm.php?search_query=" class="mim-tip-hint" title="Mutant Mouse Resource & Research Centers." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MMRRC', 'domain': 'mmrrc.org'})">MMRRC</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gene/3030/ortholog/" class="mim-tip-hint" title="Orthologous genes at NCBI." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'NCBI Orthologs', 'domain': 'ncbi.nlm.nih.gov'})">NCBI Orthologs</a></div>
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<div><a href="https://omia.org/OMIA002480/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://www.orthodb.org/?ncbi=3030" class="mim-tip-hint" title="Hierarchical catalogue of orthologs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrthoDB', 'domain': 'orthodb.org'})">OrthoDB</a></div>
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<div><a href="mim#WormbaseGeneFold" id="mimWormbaseGeneToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes."><span id="mimWormbaseGeneToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Wormbase Gene</div>
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<div id="mimWormbaseGeneFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00001150;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00001150 </a></div><div style="margin-left: 0.5em;"><a href="https://wormbase.org/db/gene/gene?name=WBGene00020347;class=Gene" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Gene', 'domain': 'wormbase.org'})">WBGene00020347 </a></div>
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</div>
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<div><a href="https://zfin.org/ZDB-GENE-031222-5" class="mim-tip-hint" title="The Zebrafish Model Organism Database." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'ZFin', 'domain': 'zfin.org'})">ZFin</a></div>
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</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="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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</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="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:600890" 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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</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="mimCellularPathways">
|
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<span class="panel-title">
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<span class="small">
|
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<a href="#mimCellularPathwaysLinksFold" id="mimCellularPathwaysLinksToggle" 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="mimCellularPathwaysLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Cellular Pathways</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="mimCellularPathwaysLinksFold" 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.genome.jp/dbget-bin/get_linkdb?-t+pathway+hsa:3030" class="mim-tip-hint" title="Kyoto Encyclopedia of Genes and Genomes; diagrams of signaling pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'KEGG', 'domain': 'genome.jp'})">KEGG</a></div>
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<div><a href="https://reactome.org/content/query?q=HADHA&species=Homo+sapiens&types=Reaction&types=Pathway&cluster=true" class="definition" title="Protein-specific information in the context of relevant cellular pathways." target="_blank" onclick="gtag('event', 'mim_outbound', {{'name': 'Reactome', 'domain': 'reactome.org'}})">Reactome</a></div>
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</div>
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</div>
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</div>
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</div>
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</div>
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</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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</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> 237999008, 726021008<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="Gene description">
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<span class="text-danger"><strong>*</strong></span>
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600890
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
|
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<h3>
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<span class="mim-font">
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HYDROXYACYL-CoA DEHYDROGENASE/3-KETOACYL-CoA THIOLASE/ENOYL-CoA HYDRATASE, ALPHA SUBUNIT; HADHA
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
|
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<h4>
|
|
<span class="mim-font">
|
|
TRIFUNCTIONAL PROTEIN, ALPHA SUBUNIT<br />
|
|
MITOCHONDRIAL TRIFUNCTIONAL PROTEIN, ALPHA SUBUNIT; MTPA<br />
|
|
LONG-CHAIN HYDROXYACYL-CoA DEHYDROGENASE; LCHAD<br />
|
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ECHA
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
|
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<a id="approvedGeneSymbols" class="mim-anchor"></a>
|
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<p>
|
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<span class="mim-text-font">
|
|
<strong><em>HGNC Approved Gene Symbol: <a href="https://www.genenames.org/tools/search/#!/genes?query=HADHA" class="mim-tip-hint" title="HUGO Gene Nomenclature Committee." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'HGNC', 'domain': 'genenames.org'})">HADHA</a></em></strong>
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</span>
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</p>
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</div>
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<div>
|
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<a id="cytogeneticLocation" class="mim-anchor"></a>
|
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<p>
|
|
<span class="mim-text-font">
|
|
<strong>
|
|
<em>
|
|
Cytogenetic location: <a href="/geneMap/2/103?start=-3&limit=10&highlight=103">2p23.3</a>
|
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|
|
Genomic coordinates <span class="small">(GRCh38)</span> : <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&position=chr2:26190635-26244632&dgv=pack&knownGene=pack&omimGene=pack" class="mim-tip-hint" title="UCSC Genome Browser; reference sequences and working draft assemblies for a large collection of genomes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'UCSC Genome Browser', 'domain': 'genome.ucsc.edu'})">2:26,190,635-26,244,632</a> </span>
|
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</em>
|
|
</strong>
|
|
<a href="https://www.ncbi.nlm.nih.gov/" target="_blank" class="small"> (from NCBI) </a>
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</span>
|
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</p>
|
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</div>
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<div>
|
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<br />
|
|
</div>
|
|
<div>
|
|
<a id="geneMap" class="mim-anchor"></a>
|
|
<div style="margin-bottom: 10px;">
|
|
<span class="h4 mim-font">
|
|
<strong>Gene-Phenotype Relationships</strong>
|
|
</span>
|
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</div>
|
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<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
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<thead>
|
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<tr class="active">
|
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<th>
|
|
Location
|
|
</th>
|
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<th>
|
|
Phenotype
|
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|
|
<span class="hidden-sm hidden-xs pull-right">
|
|
<a href="/clinicalSynopsis/table?mimNumber=609016,609016,609016,609015" class="label label-warning" onclick="gtag('event', 'mim_link', {'source': 'Entry', 'destination': 'clinicalSynopsisTable'})">
|
|
View Clinical Synopses
|
|
</a>
|
|
</span>
|
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|
</th>
|
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<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
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<th>
|
|
Inheritance
|
|
</th>
|
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<th>
|
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Phenotype <br /> mapping key
|
|
</th>
|
|
</tr>
|
|
</thead>
|
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<tbody>
|
|
|
|
<tr>
|
|
<td rowspan="4">
|
|
<span class="mim-font">
|
|
<a href="/geneMap/2/103?start=-3&limit=10&highlight=103">
|
|
2p23.3
|
|
</a>
|
|
</span>
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Mitochondrial trifunctional protein deficiency 1
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PheneGene Graphics <span class="caret"></span>
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<li><a href="/graph/radial/600890" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<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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<p>The HADHA and HADHB (<a href="/entry/143450">143450</a>) genes encode the alpha and beta subunits of the mitochondrial trifunctional protein, respectively. The heterocomplex contains 4 alpha and 4 beta subunits and catalyzes 3 steps in mitochondrial beta-oxidation of fatty acids, including the long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) step. The alpha subunit harbors the 3-hydroxyacyl-CoA dehydrogenase (<a href="https://enzyme.expasy.org/EC/1.1.1.211" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 1.1.1.211</a>) and enoyl-CoA hydratase activities (<a href="https://enzyme.expasy.org/EC/4.2.1.27" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EC\', \'domain\': \'expasy.org\'})">EC 4.2.1.27</a>) (<a href="#13" class="mim-tip-reference" title="Kamijo, T., Aoyama, T., Komiyama, A., Hashimoto, T. <strong>Structural analysis of cDNAs for subunits of human mitochondrial fatty acid beta-oxidation trifunctional protein.</strong> Biochem. Biophys. Res. Commun. 199: 818-825, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8135828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8135828</a>] [<a href="https://doi.org/10.1006/bbrc.1994.1302" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8135828">Kamijo et al., 1994</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8135828" 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="#13" class="mim-tip-reference" title="Kamijo, T., Aoyama, T., Komiyama, A., Hashimoto, T. <strong>Structural analysis of cDNAs for subunits of human mitochondrial fatty acid beta-oxidation trifunctional protein.</strong> Biochem. Biophys. Res. Commun. 199: 818-825, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8135828/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8135828</a>] [<a href="https://doi.org/10.1006/bbrc.1994.1302" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8135828">Kamijo et al. (1994)</a> identified cDNAs for the genes encoding the alpha and beta subunits of the holoenzyme. The alpha-subunit cDNA encodes an 82.598-kD precursor, which ultimately becomes the 78.969-kD mature subunit. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8135828" 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>Using rat Hadha to screen a human heart cDNA library, <a href="#16" class="mim-tip-reference" title="Sims, H. F., Brackett, J. C., Powell, C. K., Treem, W. R., Hale, D. E., Bennett, M. J., Gibson, B., Shapiro, S., Strauss, A. W. <strong>The molecular basis of pediatric long chain 3-hydroxyacyl-CoA dehydrogenase deficiency associated with maternal acute fatty liver of pregnancy.</strong> Proc. Nat. Acad. Sci. 92: 841-845, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7846063/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7846063</a>] [<a href="https://doi.org/10.1073/pnas.92.3.841" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7846063">Sims et al. (1995)</a> cloned HADHA, which encodes a 763-amino acid full-length protein, consisting of a 36-amino acid transit peptide and a 727-amino acid mature protein. HADHA shares 89% amino acid identity with its rat homolog. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7846063" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#15" class="mim-tip-reference" title="Orii, K. E., Orii, K. O., Souri, M., Orii, T., Kondo, N., Hashimoto, T., Aoyama, T. <strong>Genes for the human mitochondrial trifunctional protein alpha- and beta-subunits are divergently transcribed from a common promoter region.</strong> J. Biol. Chem. 274: 8077-8084, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10075708/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10075708</a>] [<a href="https://doi.org/10.1074/jbc.274.12.8077" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10075708">Orii et al. (1999)</a> determined that the HADHA and HADHB genes are linked in a head-to-head arrangement on opposite strands and that they have in common a 350-bp 5-prime flanking region. This region has bidirectional promoter activity with 2 critical cis elements that are activated by transcription factor SP1 (<a href="/entry/189906">189906</a>) binding. The authors concluded that expression of trifunctional protein subunits is probably coordinately regulated by a common promoter and by SP1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10075708" 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="#16" class="mim-tip-reference" title="Sims, H. F., Brackett, J. C., Powell, C. K., Treem, W. R., Hale, D. E., Bennett, M. J., Gibson, B., Shapiro, S., Strauss, A. W. <strong>The molecular basis of pediatric long chain 3-hydroxyacyl-CoA dehydrogenase deficiency associated with maternal acute fatty liver of pregnancy.</strong> Proc. Nat. Acad. Sci. 92: 841-845, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7846063/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7846063</a>] [<a href="https://doi.org/10.1073/pnas.92.3.841" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7846063">Sims et al. (1995)</a> determined that the HADHA gene contains 20 exons spanning over 52 kb. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7846063" 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>By somatic cell hybrid studies, <a href="#2" class="mim-tip-reference" title="Craig, I., Tolley, E., Bobrow, M. <strong>A preliminary analysis of the segregation of human hydroxyacyl coenzyme A dehydrogenase in human-mouse somatic cell hybrids.</strong> Birth Defects Orig. Art. Ser. XII(7): 114-117, 1976."None>Craig et al. (1976)</a> tentatively assigned the structural gene for trifunctional protein to chromosome 7. However, <a href="#9" class="mim-tip-reference" title="IJlst, L., Ruiter, J. P. N., Hoovers, J. M. N., Jakobs, M. E., Wanders, R. J. A. <strong>Common missense mutation G1528C in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: characterization and expression of the mutant protein, mutation analysis on genomic DNA and chromosomal localization of the mitochondrial trifunctional protein alpha subunit gene.</strong> J. Clin. Invest. 98: 1028-1033, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8770876/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8770876</a>] [<a href="https://doi.org/10.1172/JCI118863" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8770876">IJlst et al. (1996)</a> localized the gene for the alpha subunit of the mitochondrial trifunctional protein to 2p24.1-p23.3 by fluorescence in situ hybridization (FISH). <a href="#20" class="mim-tip-reference" title="Yang, B.-Z., Heng, H. H. Q., Ding, J.-H., Roe, C. R. <strong>The genes for the alpha and beta subunits of the mitochondrial trifunctional protein are both located in the same region on human chromosome 2p23.</strong> Genomics 37: 141-143, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8921383/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8921383</a>] [<a href="https://doi.org/10.1006/geno.1996.0533" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8921383">Yang et al. (1996)</a> mapped both the HADHA and HADHB genes to 2p23 by FISH. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8921383+8770876" 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><strong><em>Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency</em></strong></p><p>
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In LCHAD deficiency (<a href="/entry/609016">609016</a>), there is an isolated deficiency of the dehydrogenase activity with normal hydratase activity and moderately decreased thiolase activity (59% of control) (<a href="#9" class="mim-tip-reference" title="IJlst, L., Ruiter, J. P. N., Hoovers, J. M. N., Jakobs, M. E., Wanders, R. J. A. <strong>Common missense mutation G1528C in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: characterization and expression of the mutant protein, mutation analysis on genomic DNA and chromosomal localization of the mitochondrial trifunctional protein alpha subunit gene.</strong> J. Clin. Invest. 98: 1028-1033, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8770876/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8770876</a>] [<a href="https://doi.org/10.1172/JCI118863" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8770876">IJlst et al., 1996</a>). In 24 of 26 unrelated Dutch patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, <a href="#10" class="mim-tip-reference" title="IJlst, L., Wanders, R. J. A., Ushikubo, S., Kamijo, T., Hashimoto, T. <strong>Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: identification of the major disease-causing mutation in the alpha-subunit of the mitochondrial trifunctional protein.</strong> Biochim. Biophys. Acta 1215: 347-350, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7811722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7811722</a>] [<a href="https://doi.org/10.1016/0005-2760(94)90064-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7811722">IJlst et al. (1994)</a> identified a homozygous 1528G-C transversion in exon 15 of the HADHA gene, resulting in an E510Q substitution (<a href="#0001">600890.0001</a>), based on numbering from the start codon. Two patients were compound heterozygous for E510Q and another pathogenic mutation in the HADHA gene (see, e.g., <a href="#0006">600890.0006</a>-<a href="#0007">600890.0007</a>). <a href="#9" class="mim-tip-reference" title="IJlst, L., Ruiter, J. P. N., Hoovers, J. M. N., Jakobs, M. E., Wanders, R. J. A. <strong>Common missense mutation G1528C in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: characterization and expression of the mutant protein, mutation analysis on genomic DNA and chromosomal localization of the mitochondrial trifunctional protein alpha subunit gene.</strong> J. Clin. Invest. 98: 1028-1033, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8770876/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8770876</a>] [<a href="https://doi.org/10.1172/JCI118863" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8770876">IJlst et al. (1996)</a> used S. cerevisiae for expression of wildtype and mutant protein to show that the E510Q mutation is directly responsible for the loss of LCHAD activity. Furthermore, they described a newly developed method allowing identification of the mutation in genomic DNA. The finding of an 87% allele frequency of this mutation in 34 LCHAD-deficient patients made this a valuable test for prenatal diagnosis. <a href="#16" class="mim-tip-reference" title="Sims, H. F., Brackett, J. C., Powell, C. K., Treem, W. R., Hale, D. E., Bennett, M. J., Gibson, B., Shapiro, S., Strauss, A. W. <strong>The molecular basis of pediatric long chain 3-hydroxyacyl-CoA dehydrogenase deficiency associated with maternal acute fatty liver of pregnancy.</strong> Proc. Nat. Acad. Sci. 92: 841-845, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7846063/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7846063</a>] [<a href="https://doi.org/10.1073/pnas.92.3.841" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7846063">Sims et al. (1995)</a> designated the 1528G-C mutation as E474Q based on numbering of the mature HADHA protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7846063+7811722+8770876" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Ibdah, J. A., Bennett, M. J., Rinaldo, P., Zhao, Y., Gibson, B., Sims, H. F., Strauss, A. W. <strong>A fetal fatty-acid oxidation disorder as a cause of liver disease in pregnant women.</strong> New Eng. J. Med. 340: 1723-1731, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10352164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10352164</a>] [<a href="https://doi.org/10.1056/NEJM199906033402204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10352164">Ibdah et al. (1999)</a> identified mutations in the HADHA gene in 19 children with LCHAD deficiency who presented with hypoketotic hypoglycemia and fatty liver. Eight children were homozygous for the E474Q mutation, while 11 were compound heterozygous for E474Q and another pathogenic mutation. While carrying fetuses with the E474Q mutation, 79% of the heterozygous mothers had fatty liver of pregnancy or the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10352164" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Mitochondrial Trifunctional Protein Deficiency 1</em></strong></p><p>
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In mitochondrial trifunctional protein deficiency-1 (MTPD1; <a href="/entry/609105">609105</a>), all 3 activities of the protein are deficient: dehydrogenase, hydratase, and thiolase (<a href="#9" class="mim-tip-reference" title="IJlst, L., Ruiter, J. P. N., Hoovers, J. M. N., Jakobs, M. E., Wanders, R. J. A. <strong>Common missense mutation G1528C in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: characterization and expression of the mutant protein, mutation analysis on genomic DNA and chromosomal localization of the mitochondrial trifunctional protein alpha subunit gene.</strong> J. Clin. Invest. 98: 1028-1033, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8770876/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8770876</a>] [<a href="https://doi.org/10.1172/JCI118863" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8770876">IJlst et al., 1996</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8770876" 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 MTP deficiency, <a href="#1" class="mim-tip-reference" title="Brackett, J. C., Sims, H. F., Rinaldo, P., Shapiro, S., Powell, C. K., Bennett, M. J., Strauss, A. W. <strong>Two alpha subunit donor splice site mutations cause human trifunctional protein deficiency.</strong> J. Clin. Invest. 95: 2076-2082, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7738175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7738175</a>] [<a href="https://doi.org/10.1172/JCI117894" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7738175">Brackett et al. (1995)</a> identified compound heterozygosity for 2 mutations in the HADHA gene (<a href="#0003">600890.0003</a> and <a href="#0004">600890.0004</a>). The patient presented in the neonatal period with hypoglycemia and cardiomyopathy and later died unexpectedly at the age of 18 months. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7738175" 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 2 patients with MTP deficiency, <a href="#7" class="mim-tip-reference" title="Ibdah, J. A., Tein, I., Dionisi-Vici, C., Bennett, M. J., IJlst, L., Gibson, B., Wanders, R. J. A., Strauss, A. W. <strong>Mild trifunctional protein deficiency is associated with progressive neuropathy and myopathy and suggests a novel genotype-phenotype correlation.</strong> J. Clin. Invest. 102: 1193-1199, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9739053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9739053</a>] [<a href="https://doi.org/10.1172/JCI2091" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9739053">Ibdah et al. (1998)</a> identified biallelic mutations in the HADHA gene (<a href="#0008">600890.0008</a>-<a href="#0010">600890.0010</a>). The phenotype was characterized by slowly progressive chronic polyneuropathy and myopathy without hepatic or cardiac involvement. All 3 mutations were located in exon 9, which encodes a linker domain between the NH2-terminal hydratase and the COOH-terminal 3-hydroxyacyl-CoA dehydrogenase. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9739053" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Ibdah, J. A., Bennett, M. J., Rinaldo, P., Zhao, Y., Gibson, B., Sims, H. F., Strauss, A. W. <strong>A fetal fatty-acid oxidation disorder as a cause of liver disease in pregnant women.</strong> New Eng. J. Med. 340: 1723-1731, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10352164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10352164</a>] [<a href="https://doi.org/10.1056/NEJM199906033402204" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10352164">Ibdah et al. (1999)</a> reported 5 children with complete MTP deficiency who presented with neonatal dilated cardiomyopathy or progressive neuromyopathy. None had the E474Q mutation common in isolated LCHAD deficiency, and none of their mothers had liver disease during pregnancy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10352164" 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 2 unrelated patients with lethal deficiency of trifunctional protein, <a href="#17" class="mim-tip-reference" title="Spiekerkoetter, U., Eeds, A., Yue, Z., Haines, J., Strauss, A. W., Summar, M. <strong>Uniparental disomy of chromosome 2 resulting in lethal trifunctional protein deficiency due to homozygous alpha-subunit mutations.</strong> Hum. Mutat. 20: 447-451, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12442268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12442268</a>] [<a href="https://doi.org/10.1002/humu.10142" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12442268">Spiekerkoetter et al. (2002)</a> delineated apparently homozygous alpha-subunit mutations that were present in heterozygous form in both mothers, but not in either biologic father. They performed a microsatellite repeat analysis of both patients and their parents using 7 chromosome 2-specific polymorphic DNA markers and 4 non-chromosome 2 markers. In both patients, 2 chromosome 2-specific markers demonstrated maternal isodisomy of chromosome 2. The other 5 chromosome 2-specific markers were noninformative in each patient. Inheritance of alleles from chromosomes 4, 5, and 7 was consistent with paternity. <a href="#17" class="mim-tip-reference" title="Spiekerkoetter, U., Eeds, A., Yue, Z., Haines, J., Strauss, A. W., Summar, M. <strong>Uniparental disomy of chromosome 2 resulting in lethal trifunctional protein deficiency due to homozygous alpha-subunit mutations.</strong> Hum. Mutat. 20: 447-451, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12442268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12442268</a>] [<a href="https://doi.org/10.1002/humu.10142" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12442268">Spiekerkoetter et al. (2002)</a> stated that 6 of 12 trifunctional protein-deficient patients with alpha-subunit mutations had disease due to homozygosity of mutations, and 2 of these 6 via the mechanism of uniparental disomy (UPD). For very rare autosomal recessive diseases, UPD greatly alters the empiric risk for the disorder from the 25% normally used. <a href="#17" class="mim-tip-reference" title="Spiekerkoetter, U., Eeds, A., Yue, Z., Haines, J., Strauss, A. W., Summar, M. <strong>Uniparental disomy of chromosome 2 resulting in lethal trifunctional protein deficiency due to homozygous alpha-subunit mutations.</strong> Hum. Mutat. 20: 447-451, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12442268/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12442268</a>] [<a href="https://doi.org/10.1002/humu.10142" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12442268">Spiekerkoetter et al. (2002)</a> noted reports of 6 cases of maternal UPD of chromosome 2 and 2 cases of paternal UPD of chromosome 2. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12442268" 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 2 Chinese sibs with MTPD, <a href="#21" class="mim-tip-reference" title="Yang, J., Yuan, D., Tan, X., Zeng, Y., Tang, N., Chen, D., Tan, J., Cai, R., Huang, J., Yan, T. <strong>Analysis of a family with mitochondrial trifunctional protein deficiency caused by HADHA gene mutations.</strong> Molec. Med. Rep. 25: 47, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34878152/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34878152</a>] [<a href="https://doi.org/10.3892/mmr.2021.12563" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34878152">Yang et al. (2022)</a> identified compound heterozygous mutations in the HADHA gene (R235W, <a href="#0011">600890.0011</a>; G703R, <a href="#0012">600890.0012</a>). The mutations, which were identified by whole-exome sequencing and confirmed by Sanger sequencing, segregated with disease in the family. The sibs died at 3 years of age and 7 months of age in the setting of illness with fever and diarrhea. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34878152" 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="#6" class="mim-tip-reference" title="Ibdah, J. A., Paul, H., Zhao, Y., Binford, S., Salleng, K., Cline, M., Matern, D., Bennett, M. J., Rinaldo, P., Strauss, A. W. <strong>Lack of mitochondrial trifunctional protein im mice causes neonatal hypoglycemia and sudden death.</strong> J. Clin. Invest. 107: 1403-1409, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11390422/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11390422</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11390422[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/10.1172/JCI12590" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11390422">Ibdah et al. (2001)</a> found that Mtpa-null mouse fetuses accumulated long-chain fatty acid metabolites and had low birth weight. Mtpa-null mice exhibited neonatal hypoglycemia, and all died suddenly within 6 to 36 hours after birth. Histopathologic analysis showed rapid development of hepatic steatosis after birth, and later showed significant necrosis and acute degeneration of the cardiac and diaphragmatic myocytes. The findings were similar to those observed in human trifunctional protein deficiency, indicating that long-chain fatty acid oxidation is essential for fetal development and survival after birth. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11390422" 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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LCHAD DEFICIENCY WITH MATERNAL ACUTE FATTY LIVER OF PREGNANCY, INCLUDED<br />
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852769 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852769;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852769?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852769" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852769" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000009266 OR RCV000009267 OR RCV000174836 OR RCV000185933 OR RCV000535911 OR RCV000624767 OR RCV000778608 OR RCV001001910 OR RCV005003469" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009266, RCV000009267, RCV000174836, RCV000185933, RCV000535911, RCV000624767, RCV000778608, RCV001001910, RCV005003469" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009266...</a>
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<p>Based on numbering from the start codon, which was used by <a href="#10" class="mim-tip-reference" title="IJlst, L., Wanders, R. J. A., Ushikubo, S., Kamijo, T., Hashimoto, T. <strong>Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: identification of the major disease-causing mutation in the alpha-subunit of the mitochondrial trifunctional protein.</strong> Biochim. Biophys. Acta 1215: 347-350, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7811722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7811722</a>] [<a href="https://doi.org/10.1016/0005-2760(94)90064-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7811722">IJlst et al. (1994)</a>, this mutation is designated glu510-to-gln (E510Q). <a href="#16" class="mim-tip-reference" title="Sims, H. F., Brackett, J. C., Powell, C. K., Treem, W. R., Hale, D. E., Bennett, M. J., Gibson, B., Shapiro, S., Strauss, A. W. <strong>The molecular basis of pediatric long chain 3-hydroxyacyl-CoA dehydrogenase deficiency associated with maternal acute fatty liver of pregnancy.</strong> Proc. Nat. Acad. Sci. 92: 841-845, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7846063/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7846063</a>] [<a href="https://doi.org/10.1073/pnas.92.3.841" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7846063">Sims et al. (1995)</a> had designated the mutation GLU474GLN (E474Q) based on numbering of the mature protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7846063+7811722" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>LCHAD Deficiency with Maternal Acute Fatty Liver of Pregnancy</em></strong></p><p>
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<a href="#10" class="mim-tip-reference" title="IJlst, L., Wanders, R. J. A., Ushikubo, S., Kamijo, T., Hashimoto, T. <strong>Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: identification of the major disease-causing mutation in the alpha-subunit of the mitochondrial trifunctional protein.</strong> Biochim. Biophys. Acta 1215: 347-350, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7811722/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7811722</a>] [<a href="https://doi.org/10.1016/0005-2760(94)90064-7" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7811722">IJlst et al. (1994)</a> identified a 1528G-C transversion in exon 15 of the HADHA gene, resulting in an E510Q substitution, in approximately 87% of the chromosomes in patients with LCHAD deficiency (<a href="/entry/609016">609016</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7811722" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#16" class="mim-tip-reference" title="Sims, H. F., Brackett, J. C., Powell, C. K., Treem, W. R., Hale, D. E., Bennett, M. J., Gibson, B., Shapiro, S., Strauss, A. W. <strong>The molecular basis of pediatric long chain 3-hydroxyacyl-CoA dehydrogenase deficiency associated with maternal acute fatty liver of pregnancy.</strong> Proc. Nat. Acad. Sci. 92: 841-845, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7846063/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7846063</a>] [<a href="https://doi.org/10.1073/pnas.92.3.841" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7846063">Sims et al. (1995)</a> used single-strand conformation variance (SSCV) analysis of the alpha subunit of long-chain 3-hydroxyacyl-CoA dehydrogenase to determine the molecular basis of LCHAD deficiency in 3 families in which children presented with sudden unexplained death or hypoglycemia and abnormal liver enzymes (Reye-like syndrome). In all families, the mother had acute fatty liver and associated severe complications during pregnancy. The analysis in 2 affected children demonstrated homozygosity for the E474Q mutation. The third child was compound heterozygous for E474Q and Q342X (<a href="#0002">600890.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7846063" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="IJlst, L., Ruiter, J. P. N., Hoovers, J. M. N., Jakobs, M. E., Wanders, R. J. A. <strong>Common missense mutation G1528C in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: characterization and expression of the mutant protein, mutation analysis on genomic DNA and chromosomal localization of the mitochondrial trifunctional protein alpha subunit gene.</strong> J. Clin. Invest. 98: 1028-1033, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8770876/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8770876</a>] [<a href="https://doi.org/10.1172/JCI118863" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8770876">IJlst et al. (1996)</a> developed a PCR-RFLP method to identify the E474Q mutation in genomic DNA. Functional expression studies in S. cerevisiae showed that the mutation is directly responsible for the loss of LCHAD activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8770876" 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="#18" class="mim-tip-reference" title="Tyni, T., Palotie, A., Viinikka, L., Valanne, L., Salo, M. K., von Dobeln, U., Jackson, S., Wanders, R., Venizelos, N., Pihko, H. <strong>Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency with the G1528C mutation: clinical presentation of thirteen patients.</strong> J. Pediat. 130: 67-76, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9003853/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9003853</a>] [<a href="https://doi.org/10.1016/s0022-3476(97)70312-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9003853">Tyni et al. (1997)</a> discussed the clinical presentation of 13 patients with LCHAD deficiency due to a homozygous E474Q mutation. The patients had hypoglycemia, cardiomyopathy, muscle hypotonia, and hepatomegaly during the first 2 years of life. Recurrent metabolic crises had occurred in 7 patients; the other 6 had a steadily progressive course. Cholestatic liver disease, which is uncommon in beta-oxidation defects, was found in 2 patients. One patient had peripheral neuropathy, and 6 had retinopathy with focal pigmentary aggregations or retinal hypopigmentation. Radiologically, there was bilateral periventricular or focal cortical lesions in 3 patients and brain atrophy in 1. Only 1 patient, who had dietary treatment for 9 years, was alive at the age of 14 years; all others died before they were 2 years of age. The experience indicated the importance of recognizing the clinical features of LCHAD deficiency for the early institution of dietary management, which can alter the otherwise invariably poor prognosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9003853" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Ibdah, J. A., Dasouki, M. J., Strauss, A. W. <strong>Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: variable expressivity of maternal illness during pregnancy and unusual presentation with infantile cholestasis and hypocalcaemia.</strong> J. Inherit. Metab. Dis. 22: 811-814, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10518281/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10518281</a>] [<a href="https://doi.org/10.1023/a:1005506024055" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10518281">Ibdah et al. (1999)</a> reported a patient who presented at 2 months of age with generalized tonic-clonic seizure due to an acute infantile hypocalcemia and vitamin D deficiency. He also had occult, unexplained cholestatic liver disease and impairment of 25-hydroxylation of vitamin D secondary to hepatic steatosis. Sudden unexpected death occurred at 8 months. Molecular analysis revealed homozygosity for the E474Q mutation. The mother had preeclampsia during the third trimester of her pregnancy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10518281" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Mitochondrial Trifunctional Protein Deficiency 1</em></strong></p><p>
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In a man with mitochondrial trifunctional protein deficiency (MTPD1; <a href="/entry/609015">609015</a>), <a href="#14" class="mim-tip-reference" title="Liewluck, T., Mundi, M. S., Mauermann, M. L. <strong>Mitochondrial trifunctional protein deficiency: a rare cause of adult-onset rhabdomyolysis.</strong> Muscle Nerve 48: 989-991, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23868323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23868323</a>] [<a href="https://doi.org/10.1002/mus.23959" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23868323">Liewluck et al. (2013)</a> identified compound heterozygous mutations in the HADHA gene: E510Q and a splice site mutation (<a href="#0004">600890.0004</a>). The patient presented in his late forties with exercise-induced rhabdomyolysis and was found to have features of a mild sensorimotor axonal peripheral neuropathy affecting the lower limbs. Laboratory studies showed an abnormal acylcarnitine profile, suggesting a defect in HADHA activity, although patient cells were not available for study. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23868323" 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 class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852770 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852770;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852770" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852770" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In 1 family studied by <a href="#16" class="mim-tip-reference" title="Sims, H. F., Brackett, J. C., Powell, C. K., Treem, W. R., Hale, D. E., Bennett, M. J., Gibson, B., Shapiro, S., Strauss, A. W. <strong>The molecular basis of pediatric long chain 3-hydroxyacyl-CoA dehydrogenase deficiency associated with maternal acute fatty liver of pregnancy.</strong> Proc. Nat. Acad. Sci. 92: 841-845, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7846063/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7846063</a>] [<a href="https://doi.org/10.1073/pnas.92.3.841" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7846063">Sims et al. (1995)</a>, a child with LCHAD deficiency (<a href="/entry/609016">609016</a>) was compound heterozygous for 2 mutations in the HADHA gene: E474Q (<a href="#0001">600890.0001</a>) and a 1132C-T transition, resulting in a gln342-to-ter (Q342X) substitution within the cofactor NAD-binding domain of the mature protein. A truncated alpha subunit produced by this mutant allele would not contain the LCHAD active site. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7846063" 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 class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs786205088 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786205088;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs786205088" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs786205088" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000009269 OR RCV000665265 OR RCV001382535 OR RCV004566702" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009269, RCV000665265, RCV001382535, RCV004566702" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009269...</a>
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<p>In an infant with neonatal presentation of hypoglycemia and lactic aciduria and sudden unexplained death (MTPD1; <a href="/entry/609015">609015</a>) at the age of 18 months, <a href="#1" class="mim-tip-reference" title="Brackett, J. C., Sims, H. F., Rinaldo, P., Shapiro, S., Powell, C. K., Bennett, M. J., Strauss, A. W. <strong>Two alpha subunit donor splice site mutations cause human trifunctional protein deficiency.</strong> J. Clin. Invest. 95: 2076-2082, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7738175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7738175</a>] [<a href="https://doi.org/10.1172/JCI117894" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7738175">Brackett et al. (1995)</a> demonstrated compound heterozygosity for 2 different mutations in the 5-prime donor splice site following exon 3 of the HADHA gene: a paternally inherited G-to-A transition at the invariant position +1 and a maternally inherited A-to-G mutation at position +3 (<a href="#0004">600890.0004</a>). Both allelic mutations apparently caused skipping of exon 3 (71 bp), resulting in universal deletion of exon 3 in the patient's mRNA, undetectable levels of alpha-subunit protein, and complete loss of trifunctional protein. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7738175" 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 class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs781222705 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs781222705;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs781222705?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs781222705" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs781222705" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000185934 OR RCV000763079 OR RCV000984272 OR RCV004566703 OR RCV005003345" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000185934, RCV000763079, RCV000984272, RCV004566703, RCV005003345" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000185934...</a>
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<p>For discussion of the maternally inherited A-to-G mutation at position +3 of the HADHA gene that was found in compound heterozygous state in an infant with neonatal presentation of hypoglycemia and lactic aciduria and sudden unexplained death (MTPD1; <a href="/entry/609015">609015</a>) by <a href="#1" class="mim-tip-reference" title="Brackett, J. C., Sims, H. F., Rinaldo, P., Shapiro, S., Powell, C. K., Bennett, M. J., Strauss, A. W. <strong>Two alpha subunit donor splice site mutations cause human trifunctional protein deficiency.</strong> J. Clin. Invest. 95: 2076-2082, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7738175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7738175</a>] [<a href="https://doi.org/10.1172/JCI117894" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7738175">Brackett et al. (1995)</a>, see <a href="#0003">600890.0003</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7738175" 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 man with MTPD1 manifest as adult-onset exercise-induced rhabdomyolysis and mild sensorimotor axonal peripheral neuropathy, <a href="#14" class="mim-tip-reference" title="Liewluck, T., Mundi, M. S., Mauermann, M. L. <strong>Mitochondrial trifunctional protein deficiency: a rare cause of adult-onset rhabdomyolysis.</strong> Muscle Nerve 48: 989-991, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23868323/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23868323</a>] [<a href="https://doi.org/10.1002/mus.23959" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23868323">Liewluck et al. (2013)</a> identified compound heterozygous mutations in the HADHA gene: c.180+3A-G in intron 3 and E510Q (<a href="#0001">600890.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23868323" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0005 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 1</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852771 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852771;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852771?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852771" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852771" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000009271 OR RCV000820848 OR RCV001729343 OR RCV004566704 OR RCV005003346" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009271, RCV000820848, RCV001729343, RCV004566704, RCV005003346" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009271...</a>
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<p><a href="#11" class="mim-tip-reference" title="Isaacs, J. D., Sims, H. F., Powell, C. K., Bennett, M. J., Hale, D. E., Treem, W. R., Strauss, A. W. <strong>Maternal acute fatty liver of pregnancy associated with fetal trifunctional protein deficiency: molecular characterization of a novel maternal mutant allele.</strong> Pediat. Res. 40: 393-398, 1996.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8865274/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8865274</a>] [<a href="https://doi.org/10.1203/00006450-199609000-00005" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8865274">Isaacs et al. (1996)</a> described an infant with trifunctional protein deficiency-1 (MTPD1; <a href="/entry/609015">609015</a>) who was compound heterozygous for the common E474Q mutation (<a href="#0001">600890.0001</a>) causing LCHAD deficiency (<a href="/entry/609016">609016</a>) and a novel 1678C-T transition in exon 16 of the HADHA gene that results in an arg524-to-ter (R524X) substitution of the mature protein. The mother was heterozygous for the R524X mutation, and the infant's father and 2 phenotypically normal brothers were heterozygous for the E474Q mutation. Pregnancies were normal with the heterozygous sons but complicated by acute fatty liver of pregnancy with the affected son. The exon 16 mutation was confirmed by SSCV and nucleotide sequencing while both mutations were evident by ASO analysis. Quantification of the mRNA transcript from the premature termination codon mutation in exon 16 showed greatly reduced cytoplasmic levels as expected. The authors suggested that any child born to a mother with acute fatty liver of pregnancy should be screened for LCHAD or MTP deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8865274" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0006 LCHAD DEFICIENCY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs1574600309 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs1574600309;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs1574600309" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs1574600309" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000009272 OR RCV003311654 OR RCV003466842 OR RCV003764540" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009272, RCV003311654, RCV003466842, RCV003764540" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009272...</a>
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<p>Most patients with a defect in the mitochondrial trifunctional protein complex have an isolated deficiency of LCHAD activity (<a href="/entry/609016">609016</a>). In a group of 46 LCHAD-deficient patients studied enzymatically, <a href="#8" class="mim-tip-reference" title="IJlst, L., Oostheim, W., Ruiter, J. P. N., Wanders, R. J. A. <strong>Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: identification of two new mutations.</strong> J. Inherit. Metab. Dis. 20: 420-422, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9266371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9266371</a>] [<a href="https://doi.org/10.1023/a:1005310903004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9266371">IJlst et al. (1997)</a> found 12 to be compound heterozygous for the common 1528G-C mutation (<a href="#0001">600890.0001</a>) and another mutation in HADHA. <a href="#8" class="mim-tip-reference" title="IJlst, L., Oostheim, W., Ruiter, J. P. N., Wanders, R. J. A. <strong>Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: identification of two new mutations.</strong> J. Inherit. Metab. Dis. 20: 420-422, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9266371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9266371</a>] [<a href="https://doi.org/10.1023/a:1005310903004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9266371">IJlst et al. (1997)</a> described 2 new mutations found in this compound heterozygous group. One was an insertion of a C at position 2129, changing the reading frame for the alpha subunit and creating a premature stop codon at residue 733, resulting in a truncated protein that was presumed to be unstable. The second was a 1025T-C transition, resulting in a leu342-to-pro (L342P; <a href="#0007">600890.0007</a>) substitution. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9266371" 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 class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852772 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852772;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852772" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852772" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000009273" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000009273" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000009273</a>
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<p>For discussion of the leu342-to-pro (L342P) mutation in the HADHA gene that was found in compound heterozygous state in patients with LCHAD deficiency (<a href="/entry/609016">609016</a>) by <a href="#8" class="mim-tip-reference" title="IJlst, L., Oostheim, W., Ruiter, J. P. N., Wanders, R. J. A. <strong>Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: identification of two new mutations.</strong> J. Inherit. Metab. Dis. 20: 420-422, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9266371/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9266371</a>] [<a href="https://doi.org/10.1023/a:1005310903004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9266371">IJlst et al. (1997)</a>, see <a href="#0006">600890.0006</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9266371" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0008 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 1 WITH MYOPATHY AND NEUROPATHY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852773 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852773;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852773?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852773" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852773" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV004566705" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV004566705" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV004566705</a>
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<p>In a patient with trifunctional protein deficiency-1 with myopathy and neuropathy (see <a href="/entry/609015">609015</a>), <a href="#7" class="mim-tip-reference" title="Ibdah, J. A., Tein, I., Dionisi-Vici, C., Bennett, M. J., IJlst, L., Gibson, B., Wanders, R. J. A., Strauss, A. W. <strong>Mild trifunctional protein deficiency is associated with progressive neuropathy and myopathy and suggests a novel genotype-phenotype correlation.</strong> J. Clin. Invest. 102: 1193-1199, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9739053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9739053</a>] [<a href="https://doi.org/10.1172/JCI2091" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9739053">Ibdah et al. (1998)</a> identified a homozygous 845T-A transversion in exon 9 of the HADHA gene, resulting in a val246-to-asp (V246D) substitution of the mature protein. The patient was a 13-year-old boy who was born to asymptomatic first-cousin parents. He had delayed gross motor milestones and, beginning at age 20 months, he had the first of many episodes of profound weakness precipitated by fever, vomiting, or dehydration. His subsequent clinical course was characterized by slowly progressive limb-girdle myopathy with mild facial weakness and a symmetric peripheral sensorimotor axonopathy with secondary demyelination. In addition, the patient had recurrent episodes of myoglobinuria (up to 5 times per year) precipitated by prolonged exertion, infection, cold exposure, fasting, and/or stress. Muscle biopsy revealed a mild lipid-accumulative myopathy. With the introduction of frequent feeding, a high-carbohydrate low-fat diet, and preventive fatty acid oxidation measures at age 7.5 years, there was a marked reduction in the frequency of myoglobinuric episodes. There was, however, no improvement in power or endurance, and these continued to deteriorate. A trial of prednisone resulted in significant improvement in the limb-girdle myopathy, which had been sustained over 5 years, as well as a transient improvement in his peripheral neuropathy. Myoglobinuric episodes were reduced to once every 1 to 2 years and were less severe. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9739053" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0009 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 1 WITH MYOPATHY AND NEUROPATHY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs137852774 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852774;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs137852774?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852774" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852774" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<p>In a patient with trifunctional protein deficiency-1 with myopathy and neuropathy (see <a href="/entry/609015">609015</a>), <a href="#7" class="mim-tip-reference" title="Ibdah, J. A., Tein, I., Dionisi-Vici, C., Bennett, M. J., IJlst, L., Gibson, B., Wanders, R. J. A., Strauss, A. W. <strong>Mild trifunctional protein deficiency is associated with progressive neuropathy and myopathy and suggests a novel genotype-phenotype correlation.</strong> J. Clin. Invest. 102: 1193-1199, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9739053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9739053</a>] [<a href="https://doi.org/10.1172/JCI2091" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9739053">Ibdah et al. (1998)</a> identified compound heterozygosity for 2 mutations in the HADHA gene: an ile269-to-asn (I269N) substitution and an arg255-to-ter substitution (<a href="#0010">600890.0010</a>) in the mature protein. Both mutations were in exon 9. The patient was a 12-year-old boy who was born to unrelated healthy parents. The first episode of muscle weakness occurred at 13 months of age, precipitated by an upper respiratory tract infection. Thereafter there were recurrent episodes of muscle weakness and myoglobinuria precipitated by infection, fasting, exertion, or cold exposure. At long-term follow-up, the patient had slowly progressive sensorimotor polyneuropathy characterized by bilateral foot drop, contracture of the Achilles tendons, and symmetric weakness in wrist and finger extension. He did not have pigmentary retinopathy or cardiomyopathy. A high-carbohydrate/low-fat diet failed to prevent the progression of the neuromuscular manifestations. This patient had previously been reported by <a href="#3" class="mim-tip-reference" title="Dionisi Vici, C., Burlina, A. B., Bertini, E., Bachmann, C., Mazziotta, M. R. M., Zacchello, F., Sabetta, G., Hale, D. E. <strong>Progressive neuropathy and recurrent myoglobinuria in a child with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency.</strong> J. Pediat. 118: 744-746, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2019931/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2019931</a>] [<a href="https://doi.org/10.1016/s0022-3476(05)80039-3" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2019931">Dionisi Vici et al. (1991)</a>. In that report it was stated that a sister had died at the age of 3 years, probably of the same disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2019931+9739053" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>.0010 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 1 WITH MYOPATHY AND NEUROPATHY</strong>
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<div class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs137852775 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs137852775;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs137852775" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs137852775" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000589800 OR RCV000819036 OR RCV004018604 OR RCV004566707" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000589800, RCV000819036, RCV004018604, RCV004566707" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000589800...</a>
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<p>For discussion of the arg255-to-ter (R255X) mutation in the HADHA gene that was found in compound heterozygous state in a patient with trifunctional protein deficiency-1 with myopathy and neuropathy (see <a href="/entry/609015">609015</a>) by <a href="#7" class="mim-tip-reference" title="Ibdah, J. A., Tein, I., Dionisi-Vici, C., Bennett, M. J., IJlst, L., Gibson, B., Wanders, R. J. A., Strauss, A. W. <strong>Mild trifunctional protein deficiency is associated with progressive neuropathy and myopathy and suggests a novel genotype-phenotype correlation.</strong> J. Clin. Invest. 102: 1193-1199, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9739053/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9739053</a>] [<a href="https://doi.org/10.1172/JCI2091" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9739053">Ibdah et al. (1998)</a>, see <a href="#0009">600890.0009</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9739053" 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 class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown">rs786204607 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs786204607;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs786204607" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs786204607" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000169366 OR RCV000421144 OR RCV002515195 OR RCV004567367 OR RCV005025270" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000169366, RCV000421144, RCV002515195, RCV004567367, RCV005025270" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000169366...</a>
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<p>In 2 Chinese sibs with trifunctional protein deficiency-1 (MTPD1; <a href="/entry/609015">609015</a>), <a href="#21" class="mim-tip-reference" title="Yang, J., Yuan, D., Tan, X., Zeng, Y., Tang, N., Chen, D., Tan, J., Cai, R., Huang, J., Yan, T. <strong>Analysis of a family with mitochondrial trifunctional protein deficiency caused by HADHA gene mutations.</strong> Molec. Med. Rep. 25: 47, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34878152/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34878152</a>] [<a href="https://doi.org/10.3892/mmr.2021.12563" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34878152">Yang et al. (2022)</a> identified compound heterozygous mutations in the HADHA gene: a c.703C-T transition at a conserved site, resulting in an arg235-to-trp (R235W) substitution, and a c.2107G-A transition at a conserved site, resulting in a gly703-to-arg (G703R; <a href="#0012">600890.0012</a>) substitution. The mutations, which were identified by whole-exome sequencing and Sanger sequencing, segregated with disease in the family. The R235W mutation was predicted to affect the enoyl-CoA hydratase/isomerase domain and the G703R mutation was predicted to affect the 3-hydroxyacyl-CoA-dehydrogenase C-terminal domain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34878152" 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 class="btn-group"> <button type="button" class="btn btn-default btn-xs dropdown-toggle mim-font" data-toggle="dropdown"><span class="text-primary">●</span> rs200438844 <span class="caret"></span></button> <ul class="dropdown-menu"> <li><a href="https://www.ensembl.org/Homo_sapiens/Variation/Summary?v=rs200438844;toggle_HGVS_names=open" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'ensembl.org'})">Ensembl</a></li> <li><a href="https://gnomad.broadinstitute.org/variant/rs200438844?dataset=gnomad_r2_1" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'gnomad.broadinstitute.org'})" style="padding-left: 8px;"><span class="text-primary">●</span> gnomAD</a></li> <li><a href="https://www.ncbi.nlm.nih.gov/snp/?term=rs200438844" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'www.ncbi.nlm.nih.gov'})">NCBI</a></li> <li><a href="https://genome.ucsc.edu/cgi-bin/hgTracks?org=Human&db=hg38&clinvar=pack&omimAvSnp=pack&position=rs200438844" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'dbSNP', 'domain': 'genome.ucsc.edu'})">UCSC</a></li> </ul> </div>
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<a href="https://www.ncbi.nlm.nih.gov/clinvar?term=RCV000493353 OR RCV000667879 OR RCV001865540 OR RCV004568621 OR RCV005018827" target="_blank" class="btn btn-default btn-xs mim-tip-hint" title="RCV000493353, RCV000667879, RCV001865540, RCV004568621, RCV005018827" onclick="gtag('event', 'mim_outbound', {'name': 'ClinVar', 'domain': 'ncbi.nlm.nih.gov'})">RCV000493353...</a>
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<p>For discussion of the c.2107G-A transition in the HADHA gene, resulting in a gly703-to-arg (G703R) substitution, that was identified in compound heterozygous state in 2 Chinese sibs with trifunctional protein deficiency-1 (MTPD1; <a href="/entry/609015">609015</a>) by <a href="#21" class="mim-tip-reference" title="Yang, J., Yuan, D., Tan, X., Zeng, Y., Tang, N., Chen, D., Tan, J., Cai, R., Huang, J., Yan, T. <strong>Analysis of a family with mitochondrial trifunctional protein deficiency caused by HADHA gene mutations.</strong> Molec. Med. Rep. 25: 47, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34878152/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34878152</a>] [<a href="https://doi.org/10.3892/mmr.2021.12563" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34878152">Yang et al. (2022)</a>, see <a href="#0011">600890.0011</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34878152" 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="#Jackson1992" class="mim-tip-reference" title="Jackson, S., Kler, R. S., Bartlett, K., Briggs, H., Bindoff, L. A., Pourfarzam, M., Gardner-Medwin, D., Turnbull, D. M. <strong>Combined enzyme defect of mitochondrial fatty acid oxidation.</strong> J. Clin. Invest. 90: 1219-1225, 1992.">Jackson et al. (1992)</a>; <a href="#Wanders1989" class="mim-tip-reference" title="Wanders, R. J. A., Duran, M., IJlst, L., de Jager, J. P., van Gennip, A. H., Jakobs, C., Dorland, L., van Sprang, F. J. <strong>Sudden infant death and long-chain 3-hydroxyacyl-CoA dehydrogenase.</strong> Lancet 334: 52-53, 1989. Note: Originally Volume 2.">Wanders et al. (1989)</a>
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Brackett, J. C., Sims, H. F., Rinaldo, P., Shapiro, S., Powell, C. K., Bennett, M. J., Strauss, A. W.
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<strong>Two alpha subunit donor splice site mutations cause human trifunctional protein deficiency.</strong>
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J. Clin. Invest. 95: 2076-2082, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7738175/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7738175</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7738175" 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/10.1172/JCI117894" target="_blank">Full Text</a>]
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<strong>A preliminary analysis of the segregation of human hydroxyacyl coenzyme A dehydrogenase in human-mouse somatic cell hybrids.</strong>
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Birth Defects Orig. Art. Ser. XII(7): 114-117, 1976.
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Dionisi Vici, C., Burlina, A. B., Bertini, E., Bachmann, C., Mazziotta, M. R. M., Zacchello, F., Sabetta, G., Hale, D. E.
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<strong>Progressive neuropathy and recurrent myoglobinuria in a child with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency.</strong>
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J. Pediat. 118: 744-746, 1991.
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[<a href="https://doi.org/10.1056/NEJM199906033402204" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1023/a:1005506024055" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1172/JCI12590" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1172/JCI2091" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1023/a:1005310903004" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1172/JCI118863" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0005-2760(94)90064-7" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1203/00006450-199609000-00005" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1172/JCI115983" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1006/bbrc.1994.1302" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/mus.23959" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1074/jbc.274.12.8077" target="_blank">Full Text</a>]
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<a id="Yang1996" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yang, B.-Z., Heng, H. H. Q., Ding, J.-H., Roe, C. R.
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<strong>The genes for the alpha and beta subunits of the mitochondrial trifunctional protein are both located in the same region on human chromosome 2p23.</strong>
|
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Genomics 37: 141-143, 1996.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8921383/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8921383</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8921383" 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/10.1006/geno.1996.0533" target="_blank">Full Text</a>]
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</p>
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</div>
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</li>
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<li>
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<a id="21" class="mim-anchor"></a>
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<a id="Yang2022" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yang, J., Yuan, D., Tan, X., Zeng, Y., Tang, N., Chen, D., Tan, J., Cai, R., Huang, J., Yan, T.
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<strong>Analysis of a family with mitochondrial trifunctional protein deficiency caused by HADHA gene mutations.</strong>
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Molec. Med. Rep. 25: 47, 2022.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34878152/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34878152</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34878152" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.3892/mmr.2021.12563" target="_blank">Full Text</a>]
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</p>
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</ol>
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<a id="contributors" 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="mim-text-font">
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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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Hilary J. Vernon - updated : 02/13/2023
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</div>
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</div>
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<div class="row collapse" id="mimCollapseContributors">
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<div class="col-lg-offset-2 col-md-offset-4 col-sm-offset-4 col-xs-offset-2 col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 08/15/2016<br>Cassandra L. Kniffin - updated : 12/14/2007<br>Ada Hamosh - reorganized : 11/10/2004<br>Natalie E. Krasikov - updated : 2/4/2004<br>Victor A. McKusick - updated : 2/26/2003<br>Victor A. McKusick - updated : 1/2/2003<br>Patricia A. Hartz - updated : 11/4/2002<br>Ada Hamosh - updated : 4/26/2001<br>Victor A. McKusick - updated : 2/6/2001<br>Ada Hamosh - updated : 10/31/2000<br>Wilson H. Y. Lo - updated : 11/17/1999<br>Victor A. McKusick - updated : 6/4/1999<br>Victor A. McKusick - updated : 10/6/1998<br>Victor A. McKusick - updated : 3/24/1998<br>Victor A. McKusick - updated : 2/25/1998<br>Victor A. McKusick - updated : 2/12/1998<br>Victor A. McKusick - updated : 8/22/1997<br>Victor A. McKusick - updated : 6/21/1997<br>Mark H. Paalman - updated : 10/17/1996<br>Cynthia K. Ewing - updated : 10/6/1996
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</span>
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</div>
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</div>
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<div>
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<a id="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 : 10/25/1995
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</span>
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</div>
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<a id="editHistory" class="mim-anchor"></a>
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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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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alopez : 06/13/2023
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</div>
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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 : 03/27/2023<br>carol : 02/13/2023<br>carol : 08/16/2016<br>ckniffin : 08/15/2016<br>alopez : 05/18/2015<br>mcolton : 4/20/2015<br>wwang : 11/10/2010<br>terry : 4/13/2009<br>carol : 12/14/2007<br>ckniffin : 12/13/2007<br>carol : 7/17/2006<br>carol : 8/2/2005<br>terry : 8/2/2005<br>carol : 7/14/2005<br>carol : 11/16/2004<br>carol : 11/12/2004<br>carol : 11/12/2004<br>carol : 11/10/2004<br>carol : 11/10/2004<br>carol : 11/10/2004<br>carol : 2/5/2004<br>carol : 2/4/2004<br>carol : 2/4/2004<br>alopez : 2/28/2003<br>alopez : 2/28/2003<br>terry : 2/26/2003<br>carol : 1/8/2003<br>tkritzer : 1/7/2003<br>tkritzer : 1/6/2003<br>terry : 1/2/2003<br>mgross : 11/4/2002<br>mgross : 11/4/2002<br>alopez : 5/8/2001<br>terry : 4/26/2001<br>mcapotos : 2/12/2001<br>mcapotos : 2/9/2001<br>terry : 2/6/2001<br>mgross : 11/2/2000<br>terry : 10/31/2000<br>terry : 11/30/1999<br>carol : 11/17/1999<br>carol : 6/14/1999<br>carol : 6/14/1999<br>carol : 6/12/1999<br>terry : 6/4/1999<br>carol : 11/23/1998<br>carol : 10/12/1998<br>terry : 10/6/1998<br>psherman : 3/24/1998<br>dholmes : 3/5/1998<br>mark : 2/25/1998<br>mark : 2/20/1998<br>terry : 2/12/1998<br>dholmes : 10/23/1997<br>terry : 8/22/1997<br>terry : 6/24/1997<br>terry : 6/21/1997<br>mark : 6/16/1997<br>mark : 2/3/1997<br>terry : 12/18/1996<br>jamie : 10/25/1996<br>jamie : 10/25/1996<br>mark : 10/17/1996<br>mark : 10/16/1996<br>terry : 10/9/1996<br>mark : 10/6/1996<br>terry : 5/3/1996<br>mark : 4/2/1996<br>mark : 4/2/1996<br>terry : 3/23/1996<br>mimadm : 11/3/1995<br>mark : 10/25/1995
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</span>
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</div>
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<h3>
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<span class="mim-font">
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<strong>*</strong> 600890
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</span>
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</h3>
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</div>
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<div>
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<h3>
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<span class="mim-font">
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HYDROXYACYL-CoA DEHYDROGENASE/3-KETOACYL-CoA THIOLASE/ENOYL-CoA HYDRATASE, ALPHA SUBUNIT; HADHA
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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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<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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TRIFUNCTIONAL PROTEIN, ALPHA SUBUNIT<br />
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MITOCHONDRIAL TRIFUNCTIONAL PROTEIN, ALPHA SUBUNIT; MTPA<br />
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LONG-CHAIN HYDROXYACYL-CoA DEHYDROGENASE; LCHAD<br />
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ECHA
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong><em>HGNC Approved Gene Symbol: HADHA</em></strong>
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</span>
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</p>
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</div>
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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> 237999008, 726021008;
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</span>
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</p>
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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>
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<em>
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Cytogenetic location: 2p23.3
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Genomic coordinates <span class="small">(GRCh38)</span> : 2:26,190,635-26,244,632 </span>
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</em>
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</strong>
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<span class="small">(from NCBI)</span>
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</span>
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</p>
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</div>
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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>Gene-Phenotype 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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</thead>
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<tbody>
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<tr>
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<td rowspan="4">
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<span class="mim-font">
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2p23.3
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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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Fatty liver, acute, of pregnancy
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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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609016
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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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</tr>
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<tr>
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<td>
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<span class="mim-font">
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HELLP syndrome, maternal, of pregnancy
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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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609016
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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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</tr>
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<tr>
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<td>
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<span class="mim-font">
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LCHAD deficiency
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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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609016
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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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</tr>
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<tr>
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<td>
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<span class="mim-font">
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Mitochondrial trifunctional protein deficiency 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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609015
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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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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<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>TEXT</strong>
|
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</span>
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</h4>
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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>The HADHA and HADHB (143450) genes encode the alpha and beta subunits of the mitochondrial trifunctional protein, respectively. The heterocomplex contains 4 alpha and 4 beta subunits and catalyzes 3 steps in mitochondrial beta-oxidation of fatty acids, including the long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) step. The alpha subunit harbors the 3-hydroxyacyl-CoA dehydrogenase (EC 1.1.1.211) and enoyl-CoA hydratase activities (EC 4.2.1.27) (Kamijo et al., 1994). </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>Cloning and Expression</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>Kamijo et al. (1994) identified cDNAs for the genes encoding the alpha and beta subunits of the holoenzyme. The alpha-subunit cDNA encodes an 82.598-kD precursor, which ultimately becomes the 78.969-kD mature subunit. </p><p>Using rat Hadha to screen a human heart cDNA library, Sims et al. (1995) cloned HADHA, which encodes a 763-amino acid full-length protein, consisting of a 36-amino acid transit peptide and a 727-amino acid mature protein. HADHA shares 89% amino acid identity with its rat homolog. </p><p>Orii et al. (1999) determined that the HADHA and HADHB genes are linked in a head-to-head arrangement on opposite strands and that they have in common a 350-bp 5-prime flanking region. This region has bidirectional promoter activity with 2 critical cis elements that are activated by transcription factor SP1 (189906) binding. The authors concluded that expression of trifunctional protein subunits is probably coordinately regulated by a common promoter and by SP1. </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>Gene Structure</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>Sims et al. (1995) determined that the HADHA gene contains 20 exons spanning over 52 kb. </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>Mapping</strong>
|
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</span>
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>By somatic cell hybrid studies, Craig et al. (1976) tentatively assigned the structural gene for trifunctional protein to chromosome 7. However, IJlst et al. (1996) localized the gene for the alpha subunit of the mitochondrial trifunctional protein to 2p24.1-p23.3 by fluorescence in situ hybridization (FISH). Yang et al. (1996) mapped both the HADHA and HADHB genes to 2p23 by FISH. </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>Molecular Genetics</strong>
|
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency</em></strong></p><p>
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In LCHAD deficiency (609016), there is an isolated deficiency of the dehydrogenase activity with normal hydratase activity and moderately decreased thiolase activity (59% of control) (IJlst et al., 1996). In 24 of 26 unrelated Dutch patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, IJlst et al. (1994) identified a homozygous 1528G-C transversion in exon 15 of the HADHA gene, resulting in an E510Q substitution (600890.0001), based on numbering from the start codon. Two patients were compound heterozygous for E510Q and another pathogenic mutation in the HADHA gene (see, e.g., 600890.0006-600890.0007). IJlst et al. (1996) used S. cerevisiae for expression of wildtype and mutant protein to show that the E510Q mutation is directly responsible for the loss of LCHAD activity. Furthermore, they described a newly developed method allowing identification of the mutation in genomic DNA. The finding of an 87% allele frequency of this mutation in 34 LCHAD-deficient patients made this a valuable test for prenatal diagnosis. Sims et al. (1995) designated the 1528G-C mutation as E474Q based on numbering of the mature HADHA protein. </p><p>Ibdah et al. (1999) identified mutations in the HADHA gene in 19 children with LCHAD deficiency who presented with hypoketotic hypoglycemia and fatty liver. Eight children were homozygous for the E474Q mutation, while 11 were compound heterozygous for E474Q and another pathogenic mutation. While carrying fetuses with the E474Q mutation, 79% of the heterozygous mothers had fatty liver of pregnancy or the HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets). </p><p><strong><em>Mitochondrial Trifunctional Protein Deficiency 1</em></strong></p><p>
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In mitochondrial trifunctional protein deficiency-1 (MTPD1; 609105), all 3 activities of the protein are deficient: dehydrogenase, hydratase, and thiolase (IJlst et al., 1996). </p><p>In a patient with MTP deficiency, Brackett et al. (1995) identified compound heterozygosity for 2 mutations in the HADHA gene (600890.0003 and 600890.0004). The patient presented in the neonatal period with hypoglycemia and cardiomyopathy and later died unexpectedly at the age of 18 months. </p><p>In 2 patients with MTP deficiency, Ibdah et al. (1998) identified biallelic mutations in the HADHA gene (600890.0008-600890.0010). The phenotype was characterized by slowly progressive chronic polyneuropathy and myopathy without hepatic or cardiac involvement. All 3 mutations were located in exon 9, which encodes a linker domain between the NH2-terminal hydratase and the COOH-terminal 3-hydroxyacyl-CoA dehydrogenase. </p><p>Ibdah et al. (1999) reported 5 children with complete MTP deficiency who presented with neonatal dilated cardiomyopathy or progressive neuromyopathy. None had the E474Q mutation common in isolated LCHAD deficiency, and none of their mothers had liver disease during pregnancy. </p><p>In 2 unrelated patients with lethal deficiency of trifunctional protein, Spiekerkoetter et al. (2002) delineated apparently homozygous alpha-subunit mutations that were present in heterozygous form in both mothers, but not in either biologic father. They performed a microsatellite repeat analysis of both patients and their parents using 7 chromosome 2-specific polymorphic DNA markers and 4 non-chromosome 2 markers. In both patients, 2 chromosome 2-specific markers demonstrated maternal isodisomy of chromosome 2. The other 5 chromosome 2-specific markers were noninformative in each patient. Inheritance of alleles from chromosomes 4, 5, and 7 was consistent with paternity. Spiekerkoetter et al. (2002) stated that 6 of 12 trifunctional protein-deficient patients with alpha-subunit mutations had disease due to homozygosity of mutations, and 2 of these 6 via the mechanism of uniparental disomy (UPD). For very rare autosomal recessive diseases, UPD greatly alters the empiric risk for the disorder from the 25% normally used. Spiekerkoetter et al. (2002) noted reports of 6 cases of maternal UPD of chromosome 2 and 2 cases of paternal UPD of chromosome 2. </p><p>In 2 Chinese sibs with MTPD, Yang et al. (2022) identified compound heterozygous mutations in the HADHA gene (R235W, 600890.0011; G703R, 600890.0012). The mutations, which were identified by whole-exome sequencing and confirmed by Sanger sequencing, segregated with disease in the family. The sibs died at 3 years of age and 7 months of age in the setting of illness with fever and diarrhea. </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>Animal Model</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>Ibdah et al. (2001) found that Mtpa-null mouse fetuses accumulated long-chain fatty acid metabolites and had low birth weight. Mtpa-null mice exhibited neonatal hypoglycemia, and all died suddenly within 6 to 36 hours after birth. Histopathologic analysis showed rapid development of hepatic steatosis after birth, and later showed significant necrosis and acute degeneration of the cardiac and diaphragmatic myocytes. The findings were similar to those observed in human trifunctional protein deficiency, indicating that long-chain fatty acid oxidation is essential for fetal development and survival after birth. </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>ALLELIC VARIANTS</strong>
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</span>
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<strong>12 Selected Examples):</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0001 LCHAD DEFICIENCY</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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LCHAD DEFICIENCY WITH MATERNAL ACUTE FATTY LIVER OF PREGNANCY, INCLUDED<br />
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MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 1, INCLUDED
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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HADHA, GLU510GLN
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<br />
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SNP: rs137852769,
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gnomAD: rs137852769,
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ClinVar: RCV000009266, RCV000009267, RCV000174836, RCV000185933, RCV000535911, RCV000624767, RCV000778608, RCV001001910, RCV005003469
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>Based on numbering from the start codon, which was used by IJlst et al. (1994), this mutation is designated glu510-to-gln (E510Q). Sims et al. (1995) had designated the mutation GLU474GLN (E474Q) based on numbering of the mature protein. </p><p><strong><em>LCHAD Deficiency with Maternal Acute Fatty Liver of Pregnancy</em></strong></p><p>
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IJlst et al. (1994) identified a 1528G-C transversion in exon 15 of the HADHA gene, resulting in an E510Q substitution, in approximately 87% of the chromosomes in patients with LCHAD deficiency (609016). </p><p>Sims et al. (1995) used single-strand conformation variance (SSCV) analysis of the alpha subunit of long-chain 3-hydroxyacyl-CoA dehydrogenase to determine the molecular basis of LCHAD deficiency in 3 families in which children presented with sudden unexplained death or hypoglycemia and abnormal liver enzymes (Reye-like syndrome). In all families, the mother had acute fatty liver and associated severe complications during pregnancy. The analysis in 2 affected children demonstrated homozygosity for the E474Q mutation. The third child was compound heterozygous for E474Q and Q342X (600890.0002). </p><p>IJlst et al. (1996) developed a PCR-RFLP method to identify the E474Q mutation in genomic DNA. Functional expression studies in S. cerevisiae showed that the mutation is directly responsible for the loss of LCHAD activity. </p><p>Tyni et al. (1997) discussed the clinical presentation of 13 patients with LCHAD deficiency due to a homozygous E474Q mutation. The patients had hypoglycemia, cardiomyopathy, muscle hypotonia, and hepatomegaly during the first 2 years of life. Recurrent metabolic crises had occurred in 7 patients; the other 6 had a steadily progressive course. Cholestatic liver disease, which is uncommon in beta-oxidation defects, was found in 2 patients. One patient had peripheral neuropathy, and 6 had retinopathy with focal pigmentary aggregations or retinal hypopigmentation. Radiologically, there was bilateral periventricular or focal cortical lesions in 3 patients and brain atrophy in 1. Only 1 patient, who had dietary treatment for 9 years, was alive at the age of 14 years; all others died before they were 2 years of age. The experience indicated the importance of recognizing the clinical features of LCHAD deficiency for the early institution of dietary management, which can alter the otherwise invariably poor prognosis. </p><p>Ibdah et al. (1999) reported a patient who presented at 2 months of age with generalized tonic-clonic seizure due to an acute infantile hypocalcemia and vitamin D deficiency. He also had occult, unexplained cholestatic liver disease and impairment of 25-hydroxylation of vitamin D secondary to hepatic steatosis. Sudden unexpected death occurred at 8 months. Molecular analysis revealed homozygosity for the E474Q mutation. The mother had preeclampsia during the third trimester of her pregnancy. </p><p><strong><em>Mitochondrial Trifunctional Protein Deficiency 1</em></strong></p><p>
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In a man with mitochondrial trifunctional protein deficiency (MTPD1; 609015), Liewluck et al. (2013) identified compound heterozygous mutations in the HADHA gene: E510Q and a splice site mutation (600890.0004). The patient presented in his late forties with exercise-induced rhabdomyolysis and was found to have features of a mild sensorimotor axonal peripheral neuropathy affecting the lower limbs. Laboratory studies showed an abnormal acylcarnitine profile, suggesting a defect in HADHA activity, although patient cells were not available for study. </p>
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</span>
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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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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0002 LCHAD DEFICIENCY</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HADHA, GLN342TER
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<br />
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SNP: rs137852770,
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ClinVar: RCV000009268, RCV000665238, RCV001851758
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 1 family studied by Sims et al. (1995), a child with LCHAD deficiency (609016) was compound heterozygous for 2 mutations in the HADHA gene: E474Q (600890.0001) and a 1132C-T transition, resulting in a gln342-to-ter (Q342X) substitution within the cofactor NAD-binding domain of the mature protein. A truncated alpha subunit produced by this mutant allele would not contain the LCHAD active site. </p>
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</span>
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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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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0003 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HADHA, IVS3, G-A, +1
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<br />
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SNP: rs786205088,
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ClinVar: RCV000009269, RCV000665265, RCV001382535, RCV004566702
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>In an infant with neonatal presentation of hypoglycemia and lactic aciduria and sudden unexplained death (MTPD1; 609015) at the age of 18 months, Brackett et al. (1995) demonstrated compound heterozygosity for 2 different mutations in the 5-prime donor splice site following exon 3 of the HADHA gene: a paternally inherited G-to-A transition at the invariant position +1 and a maternally inherited A-to-G mutation at position +3 (600890.0004). Both allelic mutations apparently caused skipping of exon 3 (71 bp), resulting in universal deletion of exon 3 in the patient's mRNA, undetectable levels of alpha-subunit protein, and complete loss of trifunctional protein. </p>
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</span>
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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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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0004 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HADHA, IVS3DS, A-G, +3
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<br />
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SNP: rs781222705,
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gnomAD: rs781222705,
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ClinVar: RCV000185934, RCV000763079, RCV000984272, RCV004566703, RCV005003345
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>For discussion of the maternally inherited A-to-G mutation at position +3 of the HADHA gene that was found in compound heterozygous state in an infant with neonatal presentation of hypoglycemia and lactic aciduria and sudden unexplained death (MTPD1; 609015) by Brackett et al. (1995), see 600890.0003. </p><p>In a man with MTPD1 manifest as adult-onset exercise-induced rhabdomyolysis and mild sensorimotor axonal peripheral neuropathy, Liewluck et al. (2013) identified compound heterozygous mutations in the HADHA gene: c.180+3A-G in intron 3 and E510Q (600890.0001). </p>
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</span>
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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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<div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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<strong>.0005 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HADHA, ARG524TER
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<br />
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SNP: rs137852771,
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gnomAD: rs137852771,
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ClinVar: RCV000009271, RCV000820848, RCV001729343, RCV004566704, RCV005003346
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>Isaacs et al. (1996) described an infant with trifunctional protein deficiency-1 (MTPD1; 609015) who was compound heterozygous for the common E474Q mutation (600890.0001) causing LCHAD deficiency (609016) and a novel 1678C-T transition in exon 16 of the HADHA gene that results in an arg524-to-ter (R524X) substitution of the mature protein. The mother was heterozygous for the R524X mutation, and the infant's father and 2 phenotypically normal brothers were heterozygous for the E474Q mutation. Pregnancies were normal with the heterozygous sons but complicated by acute fatty liver of pregnancy with the affected son. The exon 16 mutation was confirmed by SSCV and nucleotide sequencing while both mutations were evident by ASO analysis. Quantification of the mRNA transcript from the premature termination codon mutation in exon 16 showed greatly reduced cytoplasmic levels as expected. The authors suggested that any child born to a mother with acute fatty liver of pregnancy should be screened for LCHAD or MTP deficiency. </p>
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</span>
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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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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0006 LCHAD DEFICIENCY</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HADHA, 1-BP INS, 2129C
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<br />
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SNP: rs1574600309,
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ClinVar: RCV000009272, RCV003311654, RCV003466842, RCV003764540
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>Most patients with a defect in the mitochondrial trifunctional protein complex have an isolated deficiency of LCHAD activity (609016). In a group of 46 LCHAD-deficient patients studied enzymatically, IJlst et al. (1997) found 12 to be compound heterozygous for the common 1528G-C mutation (600890.0001) and another mutation in HADHA. IJlst et al. (1997) described 2 new mutations found in this compound heterozygous group. One was an insertion of a C at position 2129, changing the reading frame for the alpha subunit and creating a premature stop codon at residue 733, resulting in a truncated protein that was presumed to be unstable. The second was a 1025T-C transition, resulting in a leu342-to-pro (L342P; 600890.0007) substitution. </p>
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</span>
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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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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0007 LCHAD DEFICIENCY</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HADHA, LEU342PRO
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<br />
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SNP: rs137852772,
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ClinVar: RCV000009273
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</span>
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</div>
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<div>
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<span class="mim-text-font">
|
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<p>For discussion of the leu342-to-pro (L342P) mutation in the HADHA gene that was found in compound heterozygous state in patients with LCHAD deficiency (609016) by IJlst et al. (1997), see 600890.0006. </p>
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</span>
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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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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0008 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 1 WITH MYOPATHY AND NEUROPATHY</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HADHA, VAL246ASP
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<br />
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SNP: rs137852773,
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gnomAD: rs137852773,
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ClinVar: RCV004566705
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with trifunctional protein deficiency-1 with myopathy and neuropathy (see 609015), Ibdah et al. (1998) identified a homozygous 845T-A transversion in exon 9 of the HADHA gene, resulting in a val246-to-asp (V246D) substitution of the mature protein. The patient was a 13-year-old boy who was born to asymptomatic first-cousin parents. He had delayed gross motor milestones and, beginning at age 20 months, he had the first of many episodes of profound weakness precipitated by fever, vomiting, or dehydration. His subsequent clinical course was characterized by slowly progressive limb-girdle myopathy with mild facial weakness and a symmetric peripheral sensorimotor axonopathy with secondary demyelination. In addition, the patient had recurrent episodes of myoglobinuria (up to 5 times per year) precipitated by prolonged exertion, infection, cold exposure, fasting, and/or stress. Muscle biopsy revealed a mild lipid-accumulative myopathy. With the introduction of frequent feeding, a high-carbohydrate low-fat diet, and preventive fatty acid oxidation measures at age 7.5 years, there was a marked reduction in the frequency of myoglobinuric episodes. There was, however, no improvement in power or endurance, and these continued to deteriorate. A trial of prednisone resulted in significant improvement in the limb-girdle myopathy, which had been sustained over 5 years, as well as a transient improvement in his peripheral neuropathy. Myoglobinuric episodes were reduced to once every 1 to 2 years and were less severe. </p>
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</span>
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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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<div>
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<div>
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<h4>
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<span class="mim-font">
|
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<strong>.0009 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 1 WITH MYOPATHY AND NEUROPATHY</strong>
|
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HADHA, ILE269ASN
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<br />
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SNP: rs137852774,
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gnomAD: rs137852774,
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ClinVar: RCV000422654, RCV000803503, RCV000984273, RCV004566706, RCV005003347
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In a patient with trifunctional protein deficiency-1 with myopathy and neuropathy (see 609015), Ibdah et al. (1998) identified compound heterozygosity for 2 mutations in the HADHA gene: an ile269-to-asn (I269N) substitution and an arg255-to-ter substitution (600890.0010) in the mature protein. Both mutations were in exon 9. The patient was a 12-year-old boy who was born to unrelated healthy parents. The first episode of muscle weakness occurred at 13 months of age, precipitated by an upper respiratory tract infection. Thereafter there were recurrent episodes of muscle weakness and myoglobinuria precipitated by infection, fasting, exertion, or cold exposure. At long-term follow-up, the patient had slowly progressive sensorimotor polyneuropathy characterized by bilateral foot drop, contracture of the Achilles tendons, and symmetric weakness in wrist and finger extension. He did not have pigmentary retinopathy or cardiomyopathy. A high-carbohydrate/low-fat diet failed to prevent the progression of the neuromuscular manifestations. This patient had previously been reported by Dionisi Vici et al. (1991). In that report it was stated that a sister had died at the age of 3 years, probably of the same disorder. </p>
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</span>
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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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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0010 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 1 WITH MYOPATHY AND NEUROPATHY</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HADHA, ARG255TER
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<br />
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SNP: rs137852775,
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ClinVar: RCV000589800, RCV000819036, RCV004018604, RCV004566707
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the arg255-to-ter (R255X) mutation in the HADHA gene that was found in compound heterozygous state in a patient with trifunctional protein deficiency-1 with myopathy and neuropathy (see 609015) by Ibdah et al. (1998), see 600890.0009. </p>
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</span>
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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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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0011 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HADHA, ARG235TRP
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<br />
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SNP: rs786204607,
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ClinVar: RCV000169366, RCV000421144, RCV002515195, RCV004567367, RCV005025270
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>In 2 Chinese sibs with trifunctional protein deficiency-1 (MTPD1; 609015), Yang et al. (2022) identified compound heterozygous mutations in the HADHA gene: a c.703C-T transition at a conserved site, resulting in an arg235-to-trp (R235W) substitution, and a c.2107G-A transition at a conserved site, resulting in a gly703-to-arg (G703R; 600890.0012) substitution. The mutations, which were identified by whole-exome sequencing and Sanger sequencing, segregated with disease in the family. The R235W mutation was predicted to affect the enoyl-CoA hydratase/isomerase domain and the G703R mutation was predicted to affect the 3-hydroxyacyl-CoA-dehydrogenase C-terminal domain. </p>
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</span>
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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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<div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>.0012 MITOCHONDRIAL TRIFUNCTIONAL PROTEIN DEFICIENCY 1</strong>
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</span>
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</h4>
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</div>
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<div>
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<span class="mim-text-font">
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HADHA, GLY703ARG
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<br />
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SNP: rs200438844,
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gnomAD: rs200438844,
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ClinVar: RCV000493353, RCV000667879, RCV001865540, RCV004568621, RCV005018827
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</span>
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</div>
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<div>
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<span class="mim-text-font">
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<p>For discussion of the c.2107G-A transition in the HADHA gene, resulting in a gly703-to-arg (G703R) substitution, that was identified in compound heterozygous state in 2 Chinese sibs with trifunctional protein deficiency-1 (MTPD1; 609015) by Yang et al. (2022), see 600890.0011. </p>
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</span>
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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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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>See Also:</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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Jackson et al. (1992); Wanders et al. (1989)
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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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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
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Brackett, J. C., Sims, H. F., Rinaldo, P., Shapiro, S., Powell, C. K., Bennett, M. J., Strauss, A. W.
|
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<strong>Two alpha subunit donor splice site mutations cause human trifunctional protein deficiency.</strong>
|
|
J. Clin. Invest. 95: 2076-2082, 1995.
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[PubMed: 7738175]
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[Full Text: https://doi.org/10.1172/JCI117894]
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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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Craig, I., Tolley, E., Bobrow, M.
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<strong>A preliminary analysis of the segregation of human hydroxyacyl coenzyme A dehydrogenase in human-mouse somatic cell hybrids.</strong>
|
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Birth Defects Orig. Art. Ser. XII(7): 114-117, 1976.
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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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Dionisi Vici, C., Burlina, A. B., Bertini, E., Bachmann, C., Mazziotta, M. R. M., Zacchello, F., Sabetta, G., Hale, D. E.
|
|
<strong>Progressive neuropathy and recurrent myoglobinuria in a child with long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency.</strong>
|
|
J. Pediat. 118: 744-746, 1991.
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[PubMed: 2019931]
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[Full Text: https://doi.org/10.1016/s0022-3476(05)80039-3]
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</p>
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<li>
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<p class="mim-text-font">
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Ibdah, J. A., Bennett, M. J., Rinaldo, P., Zhao, Y., Gibson, B., Sims, H. F., Strauss, A. W.
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<strong>A fetal fatty-acid oxidation disorder as a cause of liver disease in pregnant women.</strong>
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New Eng. J. Med. 340: 1723-1731, 1999.
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[PubMed: 10352164]
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[Full Text: https://doi.org/10.1056/NEJM199906033402204]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Ibdah, J. A., Dasouki, M. J., Strauss, A. W.
|
|
<strong>Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: variable expressivity of maternal illness during pregnancy and unusual presentation with infantile cholestasis and hypocalcaemia.</strong>
|
|
J. Inherit. Metab. Dis. 22: 811-814, 1999.
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[PubMed: 10518281]
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[Full Text: https://doi.org/10.1023/a:1005506024055]
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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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Ibdah, J. A., Paul, H., Zhao, Y., Binford, S., Salleng, K., Cline, M., Matern, D., Bennett, M. J., Rinaldo, P., Strauss, A. W.
|
|
<strong>Lack of mitochondrial trifunctional protein im mice causes neonatal hypoglycemia and sudden death.</strong>
|
|
J. Clin. Invest. 107: 1403-1409, 2001.
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[PubMed: 11390422]
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[Full Text: https://doi.org/10.1172/JCI12590]
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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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Ibdah, J. A., Tein, I., Dionisi-Vici, C., Bennett, M. J., IJlst, L., Gibson, B., Wanders, R. J. A., Strauss, A. W.
|
|
<strong>Mild trifunctional protein deficiency is associated with progressive neuropathy and myopathy and suggests a novel genotype-phenotype correlation.</strong>
|
|
J. Clin. Invest. 102: 1193-1199, 1998.
|
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|
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[PubMed: 9739053]
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[Full Text: https://doi.org/10.1172/JCI2091]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
IJlst, L., Oostheim, W., Ruiter, J. P. N., Wanders, R. J. A.
|
|
<strong>Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: identification of two new mutations.</strong>
|
|
J. Inherit. Metab. Dis. 20: 420-422, 1997.
|
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|
|
[PubMed: 9266371]
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[Full Text: https://doi.org/10.1023/a:1005310903004]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
IJlst, L., Ruiter, J. P. N., Hoovers, J. M. N., Jakobs, M. E., Wanders, R. J. A.
|
|
<strong>Common missense mutation G1528C in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: characterization and expression of the mutant protein, mutation analysis on genomic DNA and chromosomal localization of the mitochondrial trifunctional protein alpha subunit gene.</strong>
|
|
J. Clin. Invest. 98: 1028-1033, 1996.
|
|
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|
|
[PubMed: 8770876]
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|
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[Full Text: https://doi.org/10.1172/JCI118863]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
IJlst, L., Wanders, R. J. A., Ushikubo, S., Kamijo, T., Hashimoto, T.
|
|
<strong>Molecular basis of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency: identification of the major disease-causing mutation in the alpha-subunit of the mitochondrial trifunctional protein.</strong>
|
|
Biochim. Biophys. Acta 1215: 347-350, 1994.
|
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|
|
[PubMed: 7811722]
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[Full Text: https://doi.org/10.1016/0005-2760(94)90064-7]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Isaacs, J. D., Sims, H. F., Powell, C. K., Bennett, M. J., Hale, D. E., Treem, W. R., Strauss, A. W.
|
|
<strong>Maternal acute fatty liver of pregnancy associated with fetal trifunctional protein deficiency: molecular characterization of a novel maternal mutant allele.</strong>
|
|
Pediat. Res. 40: 393-398, 1996.
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|
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|
|
|
[PubMed: 8865274]
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|
|
[Full Text: https://doi.org/10.1203/00006450-199609000-00005]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Jackson, S., Kler, R. S., Bartlett, K., Briggs, H., Bindoff, L. A., Pourfarzam, M., Gardner-Medwin, D., Turnbull, D. M.
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|
<strong>Combined enzyme defect of mitochondrial fatty acid oxidation.</strong>
|
|
J. Clin. Invest. 90: 1219-1225, 1992.
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|
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[PubMed: 1401059]
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[Full Text: https://doi.org/10.1172/JCI115983]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Kamijo, T., Aoyama, T., Komiyama, A., Hashimoto, T.
|
|
<strong>Structural analysis of cDNAs for subunits of human mitochondrial fatty acid beta-oxidation trifunctional protein.</strong>
|
|
Biochem. Biophys. Res. Commun. 199: 818-825, 1994.
|
|
|
|
|
|
[PubMed: 8135828]
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|
|
[Full Text: https://doi.org/10.1006/bbrc.1994.1302]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Liewluck, T., Mundi, M. S., Mauermann, M. L.
|
|
<strong>Mitochondrial trifunctional protein deficiency: a rare cause of adult-onset rhabdomyolysis.</strong>
|
|
Muscle Nerve 48: 989-991, 2013.
|
|
|
|
|
|
[PubMed: 23868323]
|
|
|
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|
|
[Full Text: https://doi.org/10.1002/mus.23959]
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|
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Orii, K. E., Orii, K. O., Souri, M., Orii, T., Kondo, N., Hashimoto, T., Aoyama, T.
|
|
<strong>Genes for the human mitochondrial trifunctional protein alpha- and beta-subunits are divergently transcribed from a common promoter region.</strong>
|
|
J. Biol. Chem. 274: 8077-8084, 1999.
|
|
|
|
|
|
[PubMed: 10075708]
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|
|
[Full Text: https://doi.org/10.1074/jbc.274.12.8077]
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</p>
|
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</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Sims, H. F., Brackett, J. C., Powell, C. K., Treem, W. R., Hale, D. E., Bennett, M. J., Gibson, B., Shapiro, S., Strauss, A. W.
|
|
<strong>The molecular basis of pediatric long chain 3-hydroxyacyl-CoA dehydrogenase deficiency associated with maternal acute fatty liver of pregnancy.</strong>
|
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Proc. Nat. Acad. Sci. 92: 841-845, 1995.
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|
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|
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[PubMed: 7846063]
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|
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[Full Text: https://doi.org/10.1073/pnas.92.3.841]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Spiekerkoetter, U., Eeds, A., Yue, Z., Haines, J., Strauss, A. W., Summar, M.
|
|
<strong>Uniparental disomy of chromosome 2 resulting in lethal trifunctional protein deficiency due to homozygous alpha-subunit mutations.</strong>
|
|
Hum. Mutat. 20: 447-451, 2002.
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|
|
|
|
|
[PubMed: 12442268]
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|
|
[Full Text: https://doi.org/10.1002/humu.10142]
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</p>
|
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Tyni, T., Palotie, A., Viinikka, L., Valanne, L., Salo, M. K., von Dobeln, U., Jackson, S., Wanders, R., Venizelos, N., Pihko, H.
|
|
<strong>Long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency with the G1528C mutation: clinical presentation of thirteen patients.</strong>
|
|
J. Pediat. 130: 67-76, 1997.
|
|
|
|
|
|
[PubMed: 9003853]
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|
|
[Full Text: https://doi.org/10.1016/s0022-3476(97)70312-3]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Wanders, R. J. A., Duran, M., IJlst, L., de Jager, J. P., van Gennip, A. H., Jakobs, C., Dorland, L., van Sprang, F. J.
|
|
<strong>Sudden infant death and long-chain 3-hydroxyacyl-CoA dehydrogenase.</strong>
|
|
Lancet 334: 52-53, 1989. Note: Originally Volume 2.
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|
|
[PubMed: 2567831]
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|
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[Full Text: https://doi.org/10.1016/s0140-6736(89)90300-0]
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</p>
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</li>
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<li>
|
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<p class="mim-text-font">
|
|
Yang, B.-Z., Heng, H. H. Q., Ding, J.-H., Roe, C. R.
|
|
<strong>The genes for the alpha and beta subunits of the mitochondrial trifunctional protein are both located in the same region on human chromosome 2p23.</strong>
|
|
Genomics 37: 141-143, 1996.
|
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|
|
|
|
[PubMed: 8921383]
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|
[Full Text: https://doi.org/10.1006/geno.1996.0533]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
|
|
Yang, J., Yuan, D., Tan, X., Zeng, Y., Tang, N., Chen, D., Tan, J., Cai, R., Huang, J., Yan, T.
|
|
<strong>Analysis of a family with mitochondrial trifunctional protein deficiency caused by HADHA gene mutations.</strong>
|
|
Molec. Med. Rep. 25: 47, 2022.
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|
|
[PubMed: 34878152]
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[Full Text: https://doi.org/10.3892/mmr.2021.12563]
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</p>
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</li>
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</ol>
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<div>
|
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<br />
|
|
</div>
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</div>
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</div>
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<div>
|
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<div class="row">
|
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
|
|
<span class="text-nowrap mim-text-font">
|
|
Contributors:
|
|
</span>
|
|
</div>
|
|
<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
|
|
<span class="mim-text-font">
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Hilary J. Vernon - updated : 02/13/2023<br>Cassandra L. Kniffin - updated : 08/15/2016<br>Cassandra L. Kniffin - updated : 12/14/2007<br>Ada Hamosh - reorganized : 11/10/2004<br>Natalie E. Krasikov - updated : 2/4/2004<br>Victor A. McKusick - updated : 2/26/2003<br>Victor A. McKusick - updated : 1/2/2003<br>Patricia A. Hartz - updated : 11/4/2002<br>Ada Hamosh - updated : 4/26/2001<br>Victor A. McKusick - updated : 2/6/2001<br>Ada Hamosh - updated : 10/31/2000<br>Wilson H. Y. Lo - updated : 11/17/1999<br>Victor A. McKusick - updated : 6/4/1999<br>Victor A. McKusick - updated : 10/6/1998<br>Victor A. McKusick - updated : 3/24/1998<br>Victor A. McKusick - updated : 2/25/1998<br>Victor A. McKusick - updated : 2/12/1998<br>Victor A. McKusick - updated : 8/22/1997<br>Victor A. McKusick - updated : 6/21/1997<br>Mark H. Paalman - updated : 10/17/1996<br>Cynthia K. Ewing - updated : 10/6/1996
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Victor A. McKusick : 10/25/1995
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