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<title>
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Entry
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- #203750 - ALPHA-METHYLACETOACETIC ACIDURIA
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- OMIM
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<span class="h4">#203750</span>
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<strong>Table of Contents</strong>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="#description">Description</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#pathogenesis">Pathogenesis</a>
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<a href="#diagnosis">Diagnosis</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#populationGenetics">Population Genetics</a>
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<a href="#seeAlso"><strong>See Also</strong></a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=(ALPHA-METHYLACETOACETIC ACIDURIA) OR (ACAT1)" class="mim-tip-hint" title="Clinical Trials" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=713&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/8198" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://medlineplus.gov/genetics/condition/beta-ketothiolase-deficiency" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=203750[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div><a href="#mimNewbornScreeningFold" id="mimNewbornScreeningToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Information and resources for newborn screening and genetics."><span id="mimNewbornScreeningToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Newborn Screening</div>
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<div id="mimNewbornScreeningFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.acmg.net/PDFLibrary/C5-OH.pdf" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Newborn Screening', 'domain': 'www.acmg.net'})">ACMG ACT Sheet</a></div><div style="margin-left: 0.5em;"><a href="https://www.acmg.net/PDFLibrary/C5-OH-Elevated.pdf" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Newborn Screening', 'domain': 'www.acmg.net'})">ACMG Algorithm</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=134" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<div style="display: table-row">
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<div style="display: table-cell;">Animal Models</div>
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</a>
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</span>
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</span>
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<div><a href="https://www.alliancegenome.org/disease/DOID:14723" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="http://www.informatics.jax.org/disease/203750" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:14723" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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<div>
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<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> 124258007, 237953006<br />
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<strong>ORPHA:</strong> 134<br />
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<strong>DO:</strong> 14723<br />
|
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
|
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
|
|
<span class="text-danger"><strong>#</strong></span>
|
|
203750
|
|
</span>
|
|
</span>
|
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</div>
|
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</div>
|
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<div>
|
|
<a id="preferredTitle" class="mim-anchor"></a>
|
|
<h3>
|
|
<span class="mim-font">
|
|
|
|
ALPHA-METHYLACETOACETIC ACIDURIA
|
|
|
|
</span>
|
|
</h3>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
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|
|
<div>
|
|
<a id="alternativeTitles" class="mim-anchor"></a>
|
|
<div>
|
|
<p>
|
|
<span class="mim-font">
|
|
<em>Alternative titles; symbols</em>
|
|
</span>
|
|
</p>
|
|
</div>
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
2-METHYL-3-HYDROXYBUTYRIC ACIDEMIA<br />
|
|
BETA-KETOTHIOLASE DEFICIENCY<br />
|
|
MITOCHONDRIAL ACETOACETYL-CoA THIOLASE DEFICIENCY<br />
|
|
MAT DEFICIENCY<br />
|
|
T2 DEFICIENCY<br />
|
|
3-OXOTHIOLASE DEFICIENCY<br />
|
|
3-KETOTHIOLASE DEFICIENCY<br />
|
|
3-KTD DEFICIENCY
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
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<div>
|
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<br />
|
|
</div>
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</div>
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|
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<div>
|
|
<a id="phenotypeMap" class="mim-anchor"></a>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
|
|
<thead>
|
|
<tr class="active">
|
|
<th>
|
|
Location
|
|
</th>
|
|
<th>
|
|
Phenotype
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> MIM number
|
|
</th>
|
|
<th>
|
|
Inheritance
|
|
</th>
|
|
<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
|
<th>
|
|
Gene/Locus
|
|
</th>
|
|
<th>
|
|
Gene/Locus <br /> MIM number
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/11/895?start=-3&limit=10&highlight=895">
|
|
11q22.3
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Alpha-methylacetoacetic aciduria
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/203750"> 203750 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
ACAT1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607809"> 607809 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/203750" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/203750" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/203750" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
|
|
|
|
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ABDOMEN </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Gastrointestinal </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Vomiting <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422400008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422400008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/300359004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">300359004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249497008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249497008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R11.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R11.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R11.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R11.10</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0042963&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0042963</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002013" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002013</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002013" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002013</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEUROLOGIC </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Central Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Mental retardation (in some cases) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/228156007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">228156007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/110359009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">110359009</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/317-319.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">317-319.99</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714756&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714756</a>, <a href="https://bioportal.bioontology.org/search?q=C0025362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> METABOLIC FEATURES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Ketoacidosis, episodic <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1859860&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1859860</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005974" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005974</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005974" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005974</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/56051008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">56051008</a>]</span><br /> -
|
|
Dehydration <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/34095006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">34095006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E86.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E86.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/276.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">276.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011175&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011175</a>, <a href="https://bioportal.bioontology.org/search?q=C2062903&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2062903</a>, <a href="https://bioportal.bioontology.org/search?q=C4284399&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4284399</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001944" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001944</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001944" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001944</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> LABORATORY ABNORMALITIES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Increased urinary 2-methyl-3-hydroxybutyric acid <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1859852&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1859852</a>]</span><br /> -
|
|
Increased urinary 2-methylacetoacetic acid <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1859853&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1859853</a>]</span><br /> -
|
|
Increased urinary tiglylglycine <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1859854&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1859854</a>]</span><br /> -
|
|
Increased urinary 2-butanone <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1859855&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1859855</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Onset at 5-24 months<br /> -
|
|
Infections may precipitate ketotic episodes<br /> -
|
|
Patients with T2 deficiency and urinary abnormalities may be asymptomatic<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
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- Caused by mutation in the mitochondrial acetoacetyl-CoA thiolase gene (ACAT1, <a href="/entry/607809#0001">607809.0001</a>)<br />
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<p>A number sign (#) is used with this entry because alpha-methylacetoacetic aciduria is caused by homozygous or compound heterozygous mutation in the acetyl-CoA acetyltransferase-1 gene (ACAT1; <a href="/entry/607809">607809</a>) on chromosome 11q22.</p>
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<p>Alpha-methylacetoacetic aciduria, also known as 3-ketothiolase deficiency, is an inborn error of isoleucine catabolism characterized by urinary excretion of 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, tiglylglycine, and 2-butanone.</p>
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<p><a href="#2" class="mim-tip-reference" title="Daum, R. S., Lamm, P. H., Mamer, O. A., Scriver, C. R. <strong>A 'new' disorder of isoleucine catabolism.</strong> Lancet 298: 1289-1290, 1971. Note: Originally Volume II.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4143539/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4143539</a>] [<a href="https://doi.org/10.1016/s0140-6736(71)90605-2" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4143539">Daum et al. (1971)</a> first described this disorder of the sixth step in the catabolism of isoleucine, that for the conversion of alpha-methylacetoacetate to propionate in a Dutch and a Chilean family. As in many of the other inborn errors of branched-chain amino acid catabolism, the presenting clinical feature was recurrent severe metabolic acidosis. Both parents and a sib had increased amounts of alpha-methyl-beta-hydroxybutyric acid in the urine, and this was increased by administration of isoleucine. The proband also showed excessive alpha-methylacetoacetate in the urine. A follow-up of the probands by <a href="#4" class="mim-tip-reference" title="Fukao, T., Yamaguchi, S., Scriver, C. R., Dunbar, G., Wakazono, A., Kano, M., Orii, T., Hashimoto, T. <strong>Molecular studies of mitochondrial acetoacetyl-coenzyme A thiolase deficiency in the two original families.</strong> Hum. Mutat. 2: 214-220, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8103405/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8103405</a>] [<a href="https://doi.org/10.1002/humu.1380020310" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8103405">Fukao et al. (1993)</a> showed normal somatic and neuropsychologic development with no recurrence of acute metabolic decompensation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4143539+8103405" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#10" class="mim-tip-reference" title="Hillman, R. E., Keating, J. P. <strong>Beta-ketothiolase deficiency as a cause of the 'ketotic hyperglycinemia syndrome'.</strong> Pediatrics 53: 221-225, 1974.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4812006/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4812006</a>]" pmid="4812006">Hillman and Keating (1974)</a> described a female patient with the 'ketotic hyperglycinemia syndrome' (see <a href="/entry/606054">606054</a> and <a href="/entry/251000">251000</a>) and normal propionate and methylmalonate metabolism but markedly impaired catabolism of isoleucine. Studies of her urine and cultured fibroblasts suggested a defect in the beta-ketothiolase reaction which cleaves alpha-methylacetoacetyl CoA to propionyl-CoA and acetyl-CoA. The authors suggested that this was another potentially treatable condition of young infants with vomiting and acidosis. Their patient was more severely affected than those reported by <a href="#3" class="mim-tip-reference" title="Daum, R. S., Scriver, C. R., Mamer, O. A., Delvin, E., Lamm, P. H., Goldman, H. <strong>An inherited disorder of isoleucine catabolism causing accumulation of alpha-methylacetoacetate and alpha-methyl-beta-hydroxybutyrate and intermittent metabolic acidosis.</strong> Pediat. Res. 7: 149-160, 1973.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4690360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4690360</a>] [<a href="https://doi.org/10.1203/00006450-197303000-00007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4690360">Daum et al. (1973)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4812006+4690360" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#17" class="mim-tip-reference" title="Sewell, A. C., Herwig, J., Wiegratz, I., Lehnert, W., Niederhoff, H., Song, X.-Q., Kondo, N., Fukao, T. <strong>Mitochondrial acetoacetyl-CoA thiolase (beta-ketothiolase) deficiency and pregnancy.</strong> J. Inherit. Metab. Dis. 21: 441-442, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9700610/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9700610</a>] [<a href="https://doi.org/10.1023/a:1005335515166" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9700610">Sewell et al. (1998)</a> described a pregnancy in a 25-year-old woman in whom the diagnosis of MAT deficiency had been made at the age of 8 years. She presented at 32 weeks of gestation, having taken no medication other than oral iodine and iron supplements. Physical examination and routine laboratory tests were normal. Urinary organic acid analysis demonstrated a constantly elevated excretion of 2-methyl-3-hydroxybutyrate. She was begun on carnitine supplementation. She delivered a clinically normal infant by cesarean section because of cephalopelvic disproportion. At the time of report, the baby was 2 years old and had developed normally. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9700610" 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="Mrazova, L., Fukao, T., Halovd, K., Gregova, E., Kohut, V., Pribyl, D., Chrastina, P., Kondo, N., Pospisilova, E. <strong>Two novel mutations in mitochondrial acetoacetyl-CoA thiolase deficiency.</strong> J. Inherit. Metab. Dis. 28: 235-236, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15877211/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15877211</a>] [<a href="https://doi.org/10.1007/s10545-005-7497-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15877211">Mrazova et al. (2005)</a> reported a patient with T2 deficiency confirmed by genetic analysis. He presented at age 21 months with loss of consciousness after a short period of lethargy and vomiting following all-day fasting. Laboratory studies showed severe metabolic acidosis, hypoglycemia, ketonuria, hyperuricerima, and abnormal liver function tests. Organic acid profiling and enzymatic analysis indicated acetoacetyl-CoA thiolase deficiency. At age 4.5 years, he showed normal development after following a dietary regime with limited protein and lipid intake and frequent feeding. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15877211" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Grunert, S. C., Schmitt, R. N., Schlatter, S. M., Gemperle-Britschgi, C., Balci, M. C., Berg, V., Coker, M., Das, A. M., Demirkol, M., Derks, T. G. J., Gokcay, G., Ucar, S. K., and 10 others. <strong>Clinical presentation and outcome in a series of 32 patients with 2-methylacetoacetyl-coenzyme A thiolase (MAT) deficiency.</strong> Molec. Genet. Metab. 122: 67-75, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28689740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28689740</a>] [<a href="https://doi.org/10.1016/j.ymgme.2017.06.012" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="28689740">Grunert et al. (2017)</a> described 32 patients, aged 23 months to 27 years, with MAT deficiency. Twenty of the patients presented with acute metabolic decompensation, 4 were identified through newborn screening, 7 were identified presymptomatically because of an affected sib, and 1 was diagnosed due to ataxia. Three patients who were diagnosed presymptomatically had subsequent metabolic decompensations. All patients had their first decompensation between age 5 months and 3 years, and there were no neonatal or adult decompensations. The most common cause of acute metabolic decompensation was infection, including gastroenteritis or upper respiratory tract infection. The most common clinical features during decompensation were recurrent vomiting and impaired mental status, and the most common laboratory finding was ketoacidosis. Urine organic acids were reported in 28 patients; 28 had an elevation in 2-methyl-3-hydroxybutyric acid, 26 had an elevation in tiglylyglycine, and 12 had an elevation in 2-methylacetoacetic acid. Brain MRI was abnormal in 5 of 13 patients imaged; involvement of the basal ganglia was seen in 31%, involvement of the mesencephalon was seen in 15%, one patient had signs of brain atrophy, and one patient had an incomplete vertebral arch. Of 30 patients for whom developmental data were available, 24 had normal development, 4 had mild psychomotor retardation, and 2 had severe psychomotor retardation. One patient died at the age of 2 years due to severe infection. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28689740" 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>Alpha-methylacetoacetic aciduria is an autosomal recessive disorder. The family reported by <a href="#3" class="mim-tip-reference" title="Daum, R. S., Scriver, C. R., Mamer, O. A., Delvin, E., Lamm, P. H., Goldman, H. <strong>An inherited disorder of isoleucine catabolism causing accumulation of alpha-methylacetoacetate and alpha-methyl-beta-hydroxybutyrate and intermittent metabolic acidosis.</strong> Pediat. Res. 7: 149-160, 1973.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4690360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4690360</a>] [<a href="https://doi.org/10.1203/00006450-197303000-00007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4690360">Daum et al. (1973)</a> was consanguineous. The parents of the patient reported by <a href="#10" class="mim-tip-reference" title="Hillman, R. E., Keating, J. P. <strong>Beta-ketothiolase deficiency as a cause of the 'ketotic hyperglycinemia syndrome'.</strong> Pediatrics 53: 221-225, 1974.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4812006/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4812006</a>]" pmid="4812006">Hillman and Keating (1974)</a> were not related (<a href="#11" class="mim-tip-reference" title="Hillman, R. E. <strong>Personal Communication.</strong> St. Louis, Mo. 1974."None>Hillman, 1974</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4690360+4812006" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The metabolic block involves beta-ketothiolase (<a href="#6" class="mim-tip-reference" title="Gompertz, D., Saudubray, J. M., Charpentier, C., Bartlett, K., Goodey, P. A., Draffan, G. H. <strong>A defect in L-isoleucine metabolism associated with alpha-methyl-beta-hydroxybutyric and alpha-methylacetoacetic aciduria: quantitative in vivo and in vitro studies.</strong> Clin. Chim. Acta 57: 269-281, 1974.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4434646/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4434646</a>] [<a href="https://doi.org/10.1016/0009-8981(74)90407-0" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4434646">Gompertz et al., 1974</a>), the mitochondrial short-chain-length-specific thiolase (T2). <a href="#7" class="mim-tip-reference" title="Goodman, S. I. <strong>An introduction to gas chromatography-mass spectrometry and the inherited organic acidemias.</strong> Am. J. Hum. Genet. 32: 781-792, 1980.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7004178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7004178</a>]" pmid="7004178">Goodman (1980)</a> reviewed the inherited organic acidemias, with a description of gas chromatography-mass spectrometry in their detection and study. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=7004178+4434646" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In the patient reported by <a href="#12" class="mim-tip-reference" title="Hiyama, K., Sakura, N., Matsumoto, T., Kuhara, T. <strong>Deficient beta-ketothiolase activity in leukocytes from a patient with 2-methylacetoacetic aciduria.</strong> Clin. Chim. Acta 155: 189-194, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3698316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3698316</a>] [<a href="https://doi.org/10.1016/0009-8981(86)90283-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3698316">Hiyama et al. (1986)</a>, <a href="#19" class="mim-tip-reference" title="Yamaguchi, S., Orii, T., Sakura, N., Miyazawa, S., Hashimoto, T. <strong>Defect in biosynthesis of mitochondrial acetoacetyl-coenzyme A thiolase in cultured fibroblasts from a boy with 3-ketothiolase deficiency.</strong> J. Clin. Invest. 81: 813-817, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2893809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2893809</a>] [<a href="https://doi.org/10.1172/JCI113388" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2893809">Yamaguchi et al. (1988)</a> found deficiency of mitochondrial acetoacetyl-CoA thiolase; the protein appeared to be absent. Genetic complementation analysis of 7 cell lines with this deficiency suggested the existence of 3 distinct complementation groups (<a href="#18" class="mim-tip-reference" title="Sovik, O., Saudubray, J.-M., Munnich, A., Sweetman, L. <strong>Genetic complementation analysis of mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency in cultured fibroblasts.</strong> J. Inherit. Metab. Dis. 15: 359-362, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1405470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1405470</a>] [<a href="https://doi.org/10.1007/BF02435976" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1405470">Sovik et al., 1992</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1405470+3698316+2893809" 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="#12" class="mim-tip-reference" title="Hiyama, K., Sakura, N., Matsumoto, T., Kuhara, T. <strong>Deficient beta-ketothiolase activity in leukocytes from a patient with 2-methylacetoacetic aciduria.</strong> Clin. Chim. Acta 155: 189-194, 1986.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3698316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3698316</a>] [<a href="https://doi.org/10.1016/0009-8981(86)90283-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3698316">Hiyama et al. (1986)</a> suggested that the deficiency of beta-ketothiolase can be demonstrated in leukocytes, thus obviating the need for skin biopsy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3698316" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a German boy with 3-ketothiolase deficiency, born of nonconsanguineous parents, <a href="#5" class="mim-tip-reference" title="Fukao, T., Yamaguchi, S., Tomatsu, S., Orii, T., Frauendienst-Egger, G., Schrod, L., Osumi, T., Hashimoto, T. <strong>Evidence for a structural mutation (ala347-to-thr) in a German family with 3-ketothiolase deficiency.</strong> Biochem. Biophys. Res. Commun. 179: 124-129, 1991.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1715688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1715688</a>] [<a href="https://doi.org/10.1016/0006-291x(91)91343-b" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1715688">Fukao et al. (1991)</a> found compound heterozygosity for 2 mutations in the ACAT1 gene: an A347T (<a href="/entry/607609#0001">607609.0001</a>) mutation inherited from the mother, and a mutation inherited from the father that abolished expression of the gene. This was apparently the first definition of a mutant ACAT allele. The patient showed normal development until his first ketoacidotic attack at the age of 6 months, following which severe retardation developed. The diagnosis of 3-ketothiolase deficiency was made by urinary organic acid analysis during the attack. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1715688" 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 patients from the original Dutch and Chilean families with 3-ketothiolase deficiency described by <a href="#3" class="mim-tip-reference" title="Daum, R. S., Scriver, C. R., Mamer, O. A., Delvin, E., Lamm, P. H., Goldman, H. <strong>An inherited disorder of isoleucine catabolism causing accumulation of alpha-methylacetoacetate and alpha-methyl-beta-hydroxybutyrate and intermittent metabolic acidosis.</strong> Pediat. Res. 7: 149-160, 1973.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4690360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4690360</a>] [<a href="https://doi.org/10.1203/00006450-197303000-00007" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="4690360">Daum et al. (1973)</a>, <a href="#4" class="mim-tip-reference" title="Fukao, T., Yamaguchi, S., Scriver, C. R., Dunbar, G., Wakazono, A., Kano, M., Orii, T., Hashimoto, T. <strong>Molecular studies of mitochondrial acetoacetyl-coenzyme A thiolase deficiency in the two original families.</strong> Hum. Mutat. 2: 214-220, 1993.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8103405/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8103405</a>] [<a href="https://doi.org/10.1002/humu.1380020310" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="8103405">Fukao et al. (1993)</a> identified homozygosity for a splice site and a missense mutation (<a href="/entry/607809#0006">607809.0006</a> and <a href="/entry/607809#0007">607809.0007</a>), respectively, in the ACAT1 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8103405+4690360" 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 pregnant woman with 3-ketothiolase deficiency, <a href="#17" class="mim-tip-reference" title="Sewell, A. C., Herwig, J., Wiegratz, I., Lehnert, W., Niederhoff, H., Song, X.-Q., Kondo, N., Fukao, T. <strong>Mitochondrial acetoacetyl-CoA thiolase (beta-ketothiolase) deficiency and pregnancy.</strong> J. Inherit. Metab. Dis. 21: 441-442, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9700610/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9700610</a>] [<a href="https://doi.org/10.1023/a:1005335515166" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9700610">Sewell et al. (1998)</a> identified 2 mutations in the ACAT1 gene (<a href="/entry/607908#0010">607908.0010</a> and <a href="/entry/607809#0011">607809.0011</a>); her child inherited only 1 mutation. Both of her husband's alleles were normal. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9700610" 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="Sakurai, S., Fukao, T., Haapalainen, A. M., Zhang, G., Yamada, K., Lilliu, F., Yano, S., Robinson, P., Gibson, M. K., Wanders, R. J. A., Mitchell, G. A., Wierenga, R. K., Kondo, N. <strong>Kinetic and expression analyses of seven novel mutations in mitochondrial acetoacetyl-CoA thiolase (T2): identification of a Km mutant and an analysis of the mutational sites in the structure.</strong> Molec. Genet. Metab. 90: 370-378, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17236799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17236799</a>] [<a href="https://doi.org/10.1016/j.ymgme.2006.12.002" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17236799">Sakurai et al. (2007)</a> identified 7 novel and 2 previously reported mutations in 6 mitochondrial acetoacetyl-CoA thiolase-deficient patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17236799" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#14" class="mim-tip-reference" title="Monastiri, K., Amri, F., Limam, K., Kaabachi, N., Guediche, M. N. <strong>Beta-ketothiolase (2-methylacetoacetyl-CoA thiolase) deficiency: a frequent disease in Tunisia?</strong> J. Inherit. Metab. Dis. 22: 932-933, 1999.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10604145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10604145</a>] [<a href="https://doi.org/10.1023/a:1005695524913" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10604145">Monastiri et al. (1999)</a> suggested that beta-ketothiolase deficiency is unusually frequent in Tunisia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10604145" 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="#Bennett1983" class="mim-tip-reference" title="Bennett, M. J., Littlewood, J. M., MacDonald, A., Pollitt, R. J., Thompson, J. <strong>A case of beta-ketothiolase deficiency.</strong> J. Inherit. Metab. Dis. 6: 157 only, 1983.">Bennett et al. (1983)</a>; <a href="#Henry1981" class="mim-tip-reference" title="Henry, C. G., Strauss, A. W., Keating, J. P., Hillman, R. E. <strong>Congestive cardiomyopathy associated with beta-ketothiolase deficiency.</strong> J. Pediat. 99: 754-757, 1981.">Henry et al. (1981)</a>; <a href="#Iden1990" class="mim-tip-reference" title="Iden, P., Middleton, B., Robinson, B. H., Sherwood, W. G., Gibson, K. M., Sweetman, L., Sovik, O. <strong>3-Oxothiolase activities and [(14)C]-2-methylbutanoic acid incorporation in cultured fibroblasts from 13 cases of suspected 3-oxothiolase deficiency.</strong> Pediat. Res. 28: 518-522, 1990.">Iden et al. (1990)</a>
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Bennett, M. J., Littlewood, J. M., MacDonald, A., Pollitt, R. J., Thompson, J.
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<strong>A case of beta-ketothiolase deficiency.</strong>
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J. Inherit. Metab. Dis. 6: 157 only, 1983.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6422156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6422156</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6422156" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/BF02310871" target="_blank">Full Text</a>]
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Daum, R. S., Lamm, P. H., Mamer, O. A., Scriver, C. R.
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<strong>A 'new' disorder of isoleucine catabolism.</strong>
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Lancet 298: 1289-1290, 1971. Note: Originally Volume II.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4143539/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4143539</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4143539" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0140-6736(71)90605-2" target="_blank">Full Text</a>]
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Daum, R. S., Scriver, C. R., Mamer, O. A., Delvin, E., Lamm, P. H., Goldman, H.
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<strong>An inherited disorder of isoleucine catabolism causing accumulation of alpha-methylacetoacetate and alpha-methyl-beta-hydroxybutyrate and intermittent metabolic acidosis.</strong>
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Pediat. Res. 7: 149-160, 1973.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4690360/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4690360</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4690360" 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/10.1203/00006450-197303000-00007" target="_blank">Full Text</a>]
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Fukao, T., Yamaguchi, S., Scriver, C. R., Dunbar, G., Wakazono, A., Kano, M., Orii, T., Hashimoto, T.
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<strong>Molecular studies of mitochondrial acetoacetyl-coenzyme A thiolase deficiency in the two original families.</strong>
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Hum. Mutat. 2: 214-220, 1993.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8103405/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8103405</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8103405" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.1380020310" target="_blank">Full Text</a>]
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Fukao, T., Yamaguchi, S., Tomatsu, S., Orii, T., Frauendienst-Egger, G., Schrod, L., Osumi, T., Hashimoto, T.
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<strong>Evidence for a structural mutation (ala347-to-thr) in a German family with 3-ketothiolase deficiency.</strong>
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Biochem. Biophys. Res. Commun. 179: 124-129, 1991.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1715688/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1715688</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1715688" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0006-291x(91)91343-b" target="_blank">Full Text</a>]
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Gompertz, D., Saudubray, J. M., Charpentier, C., Bartlett, K., Goodey, P. A., Draffan, G. H.
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<strong>A defect in L-isoleucine metabolism associated with alpha-methyl-beta-hydroxybutyric and alpha-methylacetoacetic aciduria: quantitative in vivo and in vitro studies.</strong>
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Clin. Chim. Acta 57: 269-281, 1974.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4434646/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4434646</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4434646" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0009-8981(74)90407-0" target="_blank">Full Text</a>]
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Goodman, S. I.
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<strong>An introduction to gas chromatography-mass spectrometry and the inherited organic acidemias.</strong>
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Am. J. Hum. Genet. 32: 781-792, 1980.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7004178/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7004178</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7004178" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Grunert, S. C., Schmitt, R. N., Schlatter, S. M., Gemperle-Britschgi, C., Balci, M. C., Berg, V., Coker, M., Das, A. M., Demirkol, M., Derks, T. G. J., Gokcay, G., Ucar, S. K., and 10 others.
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<strong>Clinical presentation and outcome in a series of 32 patients with 2-methylacetoacetyl-coenzyme A thiolase (MAT) deficiency.</strong>
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Molec. Genet. Metab. 122: 67-75, 2017.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/28689740/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">28689740</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=28689740" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2017.06.012" target="_blank">Full Text</a>]
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Henry, C. G., Strauss, A. W., Keating, J. P., Hillman, R. E.
|
|
<strong>Congestive cardiomyopathy associated with beta-ketothiolase deficiency.</strong>
|
|
J. Pediat. 99: 754-757, 1981.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7299555/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7299555</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7299555" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0022-3476(81)80404-0" 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="10" class="mim-anchor"></a>
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<a id="Hillman1974" class="mim-anchor"></a>
|
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<div class="">
|
|
<p class="mim-text-font">
|
|
Hillman, R. E., Keating, J. P.
|
|
<strong>Beta-ketothiolase deficiency as a cause of the 'ketotic hyperglycinemia syndrome'.</strong>
|
|
Pediatrics 53: 221-225, 1974.
|
|
|
|
|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4812006/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4812006</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4812006" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</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="11" class="mim-anchor"></a>
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<a id="Hillman1974" class="mim-anchor"></a>
|
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<div class="">
|
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<p class="mim-text-font">
|
|
Hillman, R. E.
|
|
<strong>Personal Communication.</strong>
|
|
St. Louis, Mo. 1974.
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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="12" class="mim-anchor"></a>
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<a id="Hiyama1986" class="mim-anchor"></a>
|
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<div class="">
|
|
<p class="mim-text-font">
|
|
Hiyama, K., Sakura, N., Matsumoto, T., Kuhara, T.
|
|
<strong>Deficient beta-ketothiolase activity in leukocytes from a patient with 2-methylacetoacetic aciduria.</strong>
|
|
Clin. Chim. Acta 155: 189-194, 1986.
|
|
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3698316/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3698316</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3698316" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0009-8981(86)90283-4" 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="13" class="mim-anchor"></a>
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<a id="Iden1990" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Iden, P., Middleton, B., Robinson, B. H., Sherwood, W. G., Gibson, K. M., Sweetman, L., Sovik, O.
|
|
<strong>3-Oxothiolase activities and [(14)C]-2-methylbutanoic acid incorporation in cultured fibroblasts from 13 cases of suspected 3-oxothiolase deficiency.</strong>
|
|
Pediat. Res. 28: 518-522, 1990.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2255576/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2255576</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2255576" 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/10.1203/00006450-199011000-00021" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="14" class="mim-anchor"></a>
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<a id="Monastiri1999" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Monastiri, K., Amri, F., Limam, K., Kaabachi, N., Guediche, M. N.
|
|
<strong>Beta-ketothiolase (2-methylacetoacetyl-CoA thiolase) deficiency: a frequent disease in Tunisia?</strong>
|
|
J. Inherit. Metab. Dis. 22: 932-933, 1999.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10604145/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10604145</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10604145" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1023/a:1005695524913" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="15" class="mim-anchor"></a>
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<a id="Mrazova2005" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Mrazova, L., Fukao, T., Halovd, K., Gregova, E., Kohut, V., Pribyl, D., Chrastina, P., Kondo, N., Pospisilova, E.
|
|
<strong>Two novel mutations in mitochondrial acetoacetyl-CoA thiolase deficiency.</strong>
|
|
J. Inherit. Metab. Dis. 28: 235-236, 2005.
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|
|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15877211/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15877211</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15877211" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s10545-005-7497-6" target="_blank">Full Text</a>]
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</p>
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</div>
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<li>
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<a id="16" class="mim-anchor"></a>
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<a id="Sakurai2007" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
|
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Sakurai, S., Fukao, T., Haapalainen, A. M., Zhang, G., Yamada, K., Lilliu, F., Yano, S., Robinson, P., Gibson, M. K., Wanders, R. J. A., Mitchell, G. A., Wierenga, R. K., Kondo, N.
|
|
<strong>Kinetic and expression analyses of seven novel mutations in mitochondrial acetoacetyl-CoA thiolase (T2): identification of a Km mutant and an analysis of the mutational sites in the structure.</strong>
|
|
Molec. Genet. Metab. 90: 370-378, 2007.
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|
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17236799/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17236799</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17236799" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2006.12.002" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="17" class="mim-anchor"></a>
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<a id="Sewell1998" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sewell, A. C., Herwig, J., Wiegratz, I., Lehnert, W., Niederhoff, H., Song, X.-Q., Kondo, N., Fukao, T.
|
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<strong>Mitochondrial acetoacetyl-CoA thiolase (beta-ketothiolase) deficiency and pregnancy.</strong>
|
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J. Inherit. Metab. Dis. 21: 441-442, 1998.
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|
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9700610/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9700610</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9700610" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1023/a:1005335515166" target="_blank">Full Text</a>]
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</p>
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<li>
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<a id="18" class="mim-anchor"></a>
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<a id="Sovik1992" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Sovik, O., Saudubray, J.-M., Munnich, A., Sweetman, L.
|
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<strong>Genetic complementation analysis of mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency in cultured fibroblasts.</strong>
|
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J. Inherit. Metab. Dis. 15: 359-362, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1405470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1405470</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1405470" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/BF02435976" 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="19" class="mim-anchor"></a>
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<a id="Yamaguchi1988" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Yamaguchi, S., Orii, T., Sakura, N., Miyazawa, S., Hashimoto, T.
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<strong>Defect in biosynthesis of mitochondrial acetoacetyl-coenzyme A thiolase in cultured fibroblasts from a boy with 3-ketothiolase deficiency.</strong>
|
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J. Clin. Invest. 81: 813-817, 1988.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2893809/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2893809</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2893809" 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/JCI113388" target="_blank">Full Text</a>]
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</ol>
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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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<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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</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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Cassandra L. Kniffin - updated : 1/8/2009
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</span>
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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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Ada Hamosh - updated : 6/14/2007<br>Cassandra L. Kniffin - reorganized : 5/23/2003<br>Victor A. McKusick - updated : 12/21/1999<br>Victor A. McKusick - updated : 10/9/1998<br>Victor A. McKusick - updated : 9/18/1998<br>Victor A. McKusick - updated : 8/21/1998
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="creationDate" class="mim-anchor"></a>
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<div class="row">
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 6/2/1986
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</span>
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</div>
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</div>
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</div>
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<div>
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<a id="editHistory" 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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<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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carol : 07/12/2021
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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 : 11/25/2015<br>carol : 8/17/2015<br>terry : 2/10/2009<br>wwang : 1/15/2009<br>ckniffin : 1/8/2009<br>alopez : 6/22/2007<br>terry : 6/14/2007<br>terry : 4/18/2005<br>terry : 4/6/2005<br>carol : 5/23/2003<br>ckniffin : 5/22/2003<br>ckniffin : 3/11/2003<br>carol : 6/22/2001<br>carol : 6/22/2001<br>carol : 12/28/1999<br>terry : 12/21/1999<br>carol : 10/9/1998<br>dkim : 9/23/1998<br>terry : 9/18/1998<br>carol : 8/24/1998<br>terry : 8/21/1998<br>carol : 3/21/1998<br>mark : 9/26/1996<br>mark : 7/5/1996<br>mark : 6/17/1996<br>mimadm : 11/12/1995<br>carol : 11/18/1994<br>jason : 7/14/1994<br>davew : 6/1/1994<br>warfield : 4/14/1994<br>carol : 12/2/1993
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</span>
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</div>
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</div>
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</div>
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</div>
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</div>
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<div class="container visible-print-block">
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<div class="row">
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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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<strong>#</strong> 203750
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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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ALPHA-METHYLACETOACETIC ACIDURIA
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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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<div >
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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2-METHYL-3-HYDROXYBUTYRIC ACIDEMIA<br />
|
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BETA-KETOTHIOLASE DEFICIENCY<br />
|
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MITOCHONDRIAL ACETOACETYL-CoA THIOLASE DEFICIENCY<br />
|
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MAT DEFICIENCY<br />
|
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T2 DEFICIENCY<br />
|
|
3-OXOTHIOLASE DEFICIENCY<br />
|
|
3-KETOTHIOLASE DEFICIENCY<br />
|
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3-KTD DEFICIENCY
|
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<p>
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<span class="mim-text-font">
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<strong>SNOMEDCT:</strong> 124258007, 237953006;
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<strong>ORPHA:</strong> 134;
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<strong>DO:</strong> 14723;
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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 />
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</div>
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<div>
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<h4>
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<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
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</span>
|
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</h4>
|
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<div>
|
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<table class="table table-bordered table-condensed small mim-table-padding">
|
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<thead>
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<tr class="active">
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<th>
|
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
|
|
Phenotype <br /> MIM number
|
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</th>
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<th>
|
|
Inheritance
|
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</th>
|
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<th>
|
|
Phenotype <br /> mapping key
|
|
</th>
|
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<th>
|
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Gene/Locus
|
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</th>
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<th>
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Gene/Locus <br /> MIM number
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td>
|
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<span class="mim-font">
|
|
11q22.3
|
|
</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
Alpha-methylacetoacetic aciduria
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
203750
|
|
</span>
|
|
</td>
|
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<td>
|
|
<span class="mim-font">
|
|
Autosomal recessive
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
ACAT1
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
607809
|
|
</span>
|
|
</td>
|
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</tr>
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|
|
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</tbody>
|
|
</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">
|
|
<strong>TEXT</strong>
|
|
</span>
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</h4>
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<span class="mim-text-font">
|
|
<p>A number sign (#) is used with this entry because alpha-methylacetoacetic aciduria is caused by homozygous or compound heterozygous mutation in the acetyl-CoA acetyltransferase-1 gene (ACAT1; 607809) on chromosome 11q22.</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">
|
|
<strong>Description</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
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<span class="mim-text-font">
|
|
<p>Alpha-methylacetoacetic aciduria, also known as 3-ketothiolase deficiency, is an inborn error of isoleucine catabolism characterized by urinary excretion of 2-methyl-3-hydroxybutyric acid, 2-methylacetoacetic acid, tiglylglycine, and 2-butanone.</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">
|
|
<strong>Clinical Features</strong>
|
|
</span>
|
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</h4>
|
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</div>
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<span class="mim-text-font">
|
|
<p>Daum et al. (1971) first described this disorder of the sixth step in the catabolism of isoleucine, that for the conversion of alpha-methylacetoacetate to propionate in a Dutch and a Chilean family. As in many of the other inborn errors of branched-chain amino acid catabolism, the presenting clinical feature was recurrent severe metabolic acidosis. Both parents and a sib had increased amounts of alpha-methyl-beta-hydroxybutyric acid in the urine, and this was increased by administration of isoleucine. The proband also showed excessive alpha-methylacetoacetate in the urine. A follow-up of the probands by Fukao et al. (1993) showed normal somatic and neuropsychologic development with no recurrence of acute metabolic decompensation. </p><p>Hillman and Keating (1974) described a female patient with the 'ketotic hyperglycinemia syndrome' (see 606054 and 251000) and normal propionate and methylmalonate metabolism but markedly impaired catabolism of isoleucine. Studies of her urine and cultured fibroblasts suggested a defect in the beta-ketothiolase reaction which cleaves alpha-methylacetoacetyl CoA to propionyl-CoA and acetyl-CoA. The authors suggested that this was another potentially treatable condition of young infants with vomiting and acidosis. Their patient was more severely affected than those reported by Daum et al. (1973). </p><p>Sewell et al. (1998) described a pregnancy in a 25-year-old woman in whom the diagnosis of MAT deficiency had been made at the age of 8 years. She presented at 32 weeks of gestation, having taken no medication other than oral iodine and iron supplements. Physical examination and routine laboratory tests were normal. Urinary organic acid analysis demonstrated a constantly elevated excretion of 2-methyl-3-hydroxybutyrate. She was begun on carnitine supplementation. She delivered a clinically normal infant by cesarean section because of cephalopelvic disproportion. At the time of report, the baby was 2 years old and had developed normally. </p><p>Mrazova et al. (2005) reported a patient with T2 deficiency confirmed by genetic analysis. He presented at age 21 months with loss of consciousness after a short period of lethargy and vomiting following all-day fasting. Laboratory studies showed severe metabolic acidosis, hypoglycemia, ketonuria, hyperuricerima, and abnormal liver function tests. Organic acid profiling and enzymatic analysis indicated acetoacetyl-CoA thiolase deficiency. At age 4.5 years, he showed normal development after following a dietary regime with limited protein and lipid intake and frequent feeding. </p><p>Grunert et al. (2017) described 32 patients, aged 23 months to 27 years, with MAT deficiency. Twenty of the patients presented with acute metabolic decompensation, 4 were identified through newborn screening, 7 were identified presymptomatically because of an affected sib, and 1 was diagnosed due to ataxia. Three patients who were diagnosed presymptomatically had subsequent metabolic decompensations. All patients had their first decompensation between age 5 months and 3 years, and there were no neonatal or adult decompensations. The most common cause of acute metabolic decompensation was infection, including gastroenteritis or upper respiratory tract infection. The most common clinical features during decompensation were recurrent vomiting and impaired mental status, and the most common laboratory finding was ketoacidosis. Urine organic acids were reported in 28 patients; 28 had an elevation in 2-methyl-3-hydroxybutyric acid, 26 had an elevation in tiglylyglycine, and 12 had an elevation in 2-methylacetoacetic acid. Brain MRI was abnormal in 5 of 13 patients imaged; involvement of the basal ganglia was seen in 31%, involvement of the mesencephalon was seen in 15%, one patient had signs of brain atrophy, and one patient had an incomplete vertebral arch. Of 30 patients for whom developmental data were available, 24 had normal development, 4 had mild psychomotor retardation, and 2 had severe psychomotor retardation. One patient died at the age of 2 years due to severe infection. </p>
|
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</span>
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<div>
|
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<br />
|
|
</div>
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|
|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Inheritance</strong>
|
|
</span>
|
|
</h4>
|
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</div>
|
|
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|
|
|
|
<span class="mim-text-font">
|
|
<p>Alpha-methylacetoacetic aciduria is an autosomal recessive disorder. The family reported by Daum et al. (1973) was consanguineous. The parents of the patient reported by Hillman and Keating (1974) were not related (Hillman, 1974). </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>
|
|
<span class="mim-font">
|
|
<strong>Pathogenesis</strong>
|
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</span>
|
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</h4>
|
|
</div>
|
|
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|
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<span class="mim-text-font">
|
|
<p>The metabolic block involves beta-ketothiolase (Gompertz et al., 1974), the mitochondrial short-chain-length-specific thiolase (T2). Goodman (1980) reviewed the inherited organic acidemias, with a description of gas chromatography-mass spectrometry in their detection and study. </p><p>In the patient reported by Hiyama et al. (1986), Yamaguchi et al. (1988) found deficiency of mitochondrial acetoacetyl-CoA thiolase; the protein appeared to be absent. Genetic complementation analysis of 7 cell lines with this deficiency suggested the existence of 3 distinct complementation groups (Sovik et al., 1992). </p>
|
|
</span>
|
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<div>
|
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<br />
|
|
</div>
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|
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|
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<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Diagnosis</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Hiyama et al. (1986) suggested that the deficiency of beta-ketothiolase can be demonstrated in leukocytes, thus obviating the need for skin biopsy. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Molecular Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>In a German boy with 3-ketothiolase deficiency, born of nonconsanguineous parents, Fukao et al. (1991) found compound heterozygosity for 2 mutations in the ACAT1 gene: an A347T (607609.0001) mutation inherited from the mother, and a mutation inherited from the father that abolished expression of the gene. This was apparently the first definition of a mutant ACAT allele. The patient showed normal development until his first ketoacidotic attack at the age of 6 months, following which severe retardation developed. The diagnosis of 3-ketothiolase deficiency was made by urinary organic acid analysis during the attack. </p><p>In patients from the original Dutch and Chilean families with 3-ketothiolase deficiency described by Daum et al. (1973), Fukao et al. (1993) identified homozygosity for a splice site and a missense mutation (607809.0006 and 607809.0007), respectively, in the ACAT1 gene. </p><p>In a pregnant woman with 3-ketothiolase deficiency, Sewell et al. (1998) identified 2 mutations in the ACAT1 gene (607908.0010 and 607809.0011); her child inherited only 1 mutation. Both of her husband's alleles were normal. </p><p>Sakurai et al. (2007) identified 7 novel and 2 previously reported mutations in 6 mitochondrial acetoacetyl-CoA thiolase-deficient patients. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>Population Genetics</strong>
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
|
|
|
|
|
|
<span class="mim-text-font">
|
|
<p>Monastiri et al. (1999) suggested that beta-ketothiolase deficiency is unusually frequent in Tunisia. </p>
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
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|
|
|
</div>
|
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|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>See Also:</strong>
|
|
</span>
|
|
</h4>
|
|
<span class="mim-text-font">
|
|
Bennett et al. (1983); Henry et al. (1981); Iden et al. (1990)
|
|
</span>
|
|
<div>
|
|
<br />
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<h4>
|
|
<span class="mim-font">
|
|
<strong>REFERENCES</strong>
|
|
</span>
|
|
</h4>
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
<div>
|
|
<ol>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Bennett, M. J., Littlewood, J. M., MacDonald, A., Pollitt, R. J., Thompson, J.
|
|
<strong>A case of beta-ketothiolase deficiency.</strong>
|
|
J. Inherit. Metab. Dis. 6: 157 only, 1983.
|
|
|
|
|
|
[PubMed: 6422156]
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|
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[Full Text: https://doi.org/10.1007/BF02310871]
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Daum, R. S., Lamm, P. H., Mamer, O. A., Scriver, C. R.
|
|
<strong>A 'new' disorder of isoleucine catabolism.</strong>
|
|
Lancet 298: 1289-1290, 1971. Note: Originally Volume II.
|
|
|
|
|
|
[PubMed: 4143539]
|
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[Full Text: https://doi.org/10.1016/s0140-6736(71)90605-2]
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</p>
|
|
</li>
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<li>
|
|
<p class="mim-text-font">
|
|
Daum, R. S., Scriver, C. R., Mamer, O. A., Delvin, E., Lamm, P. H., Goldman, H.
|
|
<strong>An inherited disorder of isoleucine catabolism causing accumulation of alpha-methylacetoacetate and alpha-methyl-beta-hydroxybutyrate and intermittent metabolic acidosis.</strong>
|
|
Pediat. Res. 7: 149-160, 1973.
|
|
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|
|
[PubMed: 4690360]
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|
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[Full Text: https://doi.org/10.1203/00006450-197303000-00007]
|
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fukao, T., Yamaguchi, S., Scriver, C. R., Dunbar, G., Wakazono, A., Kano, M., Orii, T., Hashimoto, T.
|
|
<strong>Molecular studies of mitochondrial acetoacetyl-coenzyme A thiolase deficiency in the two original families.</strong>
|
|
Hum. Mutat. 2: 214-220, 1993.
|
|
|
|
|
|
[PubMed: 8103405]
|
|
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|
|
[Full Text: https://doi.org/10.1002/humu.1380020310]
|
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|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Fukao, T., Yamaguchi, S., Tomatsu, S., Orii, T., Frauendienst-Egger, G., Schrod, L., Osumi, T., Hashimoto, T.
|
|
<strong>Evidence for a structural mutation (ala347-to-thr) in a German family with 3-ketothiolase deficiency.</strong>
|
|
Biochem. Biophys. Res. Commun. 179: 124-129, 1991.
|
|
|
|
|
|
[PubMed: 1715688]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0006-291x(91)91343-b]
|
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|
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</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Gompertz, D., Saudubray, J. M., Charpentier, C., Bartlett, K., Goodey, P. A., Draffan, G. H.
|
|
<strong>A defect in L-isoleucine metabolism associated with alpha-methyl-beta-hydroxybutyric and alpha-methylacetoacetic aciduria: quantitative in vivo and in vitro studies.</strong>
|
|
Clin. Chim. Acta 57: 269-281, 1974.
|
|
|
|
|
|
[PubMed: 4434646]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0009-8981(74)90407-0]
|
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|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Goodman, S. I.
|
|
<strong>An introduction to gas chromatography-mass spectrometry and the inherited organic acidemias.</strong>
|
|
Am. J. Hum. Genet. 32: 781-792, 1980.
|
|
|
|
|
|
[PubMed: 7004178]
|
|
|
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|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Grunert, S. C., Schmitt, R. N., Schlatter, S. M., Gemperle-Britschgi, C., Balci, M. C., Berg, V., Coker, M., Das, A. M., Demirkol, M., Derks, T. G. J., Gokcay, G., Ucar, S. K., and 10 others.
|
|
<strong>Clinical presentation and outcome in a series of 32 patients with 2-methylacetoacetyl-coenzyme A thiolase (MAT) deficiency.</strong>
|
|
Molec. Genet. Metab. 122: 67-75, 2017.
|
|
|
|
|
|
[PubMed: 28689740]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2017.06.012]
|
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|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Henry, C. G., Strauss, A. W., Keating, J. P., Hillman, R. E.
|
|
<strong>Congestive cardiomyopathy associated with beta-ketothiolase deficiency.</strong>
|
|
J. Pediat. 99: 754-757, 1981.
|
|
|
|
|
|
[PubMed: 7299555]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/s0022-3476(81)80404-0]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hillman, R. E., Keating, J. P.
|
|
<strong>Beta-ketothiolase deficiency as a cause of the 'ketotic hyperglycinemia syndrome'.</strong>
|
|
Pediatrics 53: 221-225, 1974.
|
|
|
|
|
|
[PubMed: 4812006]
|
|
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hillman, R. E.
|
|
<strong>Personal Communication.</strong>
|
|
St. Louis, Mo. 1974.
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Hiyama, K., Sakura, N., Matsumoto, T., Kuhara, T.
|
|
<strong>Deficient beta-ketothiolase activity in leukocytes from a patient with 2-methylacetoacetic aciduria.</strong>
|
|
Clin. Chim. Acta 155: 189-194, 1986.
|
|
|
|
|
|
[PubMed: 3698316]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1016/0009-8981(86)90283-4]
|
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|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Iden, P., Middleton, B., Robinson, B. H., Sherwood, W. G., Gibson, K. M., Sweetman, L., Sovik, O.
|
|
<strong>3-Oxothiolase activities and [(14)C]-2-methylbutanoic acid incorporation in cultured fibroblasts from 13 cases of suspected 3-oxothiolase deficiency.</strong>
|
|
Pediat. Res. 28: 518-522, 1990.
|
|
|
|
|
|
[PubMed: 2255576]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1203/00006450-199011000-00021]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Monastiri, K., Amri, F., Limam, K., Kaabachi, N., Guediche, M. N.
|
|
<strong>Beta-ketothiolase (2-methylacetoacetyl-CoA thiolase) deficiency: a frequent disease in Tunisia?</strong>
|
|
J. Inherit. Metab. Dis. 22: 932-933, 1999.
|
|
|
|
|
|
[PubMed: 10604145]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1023/a:1005695524913]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Mrazova, L., Fukao, T., Halovd, K., Gregova, E., Kohut, V., Pribyl, D., Chrastina, P., Kondo, N., Pospisilova, E.
|
|
<strong>Two novel mutations in mitochondrial acetoacetyl-CoA thiolase deficiency.</strong>
|
|
J. Inherit. Metab. Dis. 28: 235-236, 2005.
|
|
|
|
|
|
[PubMed: 15877211]
|
|
|
|
|
|
[Full Text: https://doi.org/10.1007/s10545-005-7497-6]
|
|
|
|
|
|
</p>
|
|
</li>
|
|
|
|
<li>
|
|
<p class="mim-text-font">
|
|
Sakurai, S., Fukao, T., Haapalainen, A. M., Zhang, G., Yamada, K., Lilliu, F., Yano, S., Robinson, P., Gibson, M. K., Wanders, R. J. A., Mitchell, G. A., Wierenga, R. K., Kondo, N.
|
|
<strong>Kinetic and expression analyses of seven novel mutations in mitochondrial acetoacetyl-CoA thiolase (T2): identification of a Km mutant and an analysis of the mutational sites in the structure.</strong>
|
|
Molec. Genet. Metab. 90: 370-378, 2007.
|
|
|
|
|
|
[PubMed: 17236799]
|
|
|
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|
|
[Full Text: https://doi.org/10.1016/j.ymgme.2006.12.002]
|
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|
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</p>
|
|
</li>
|
|
|
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<li>
|
|
<p class="mim-text-font">
|
|
Sewell, A. C., Herwig, J., Wiegratz, I., Lehnert, W., Niederhoff, H., Song, X.-Q., Kondo, N., Fukao, T.
|
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<strong>Mitochondrial acetoacetyl-CoA thiolase (beta-ketothiolase) deficiency and pregnancy.</strong>
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J. Inherit. Metab. Dis. 21: 441-442, 1998.
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[PubMed: 9700610]
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[Full Text: https://doi.org/10.1023/a:1005335515166]
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Sovik, O., Saudubray, J.-M., Munnich, A., Sweetman, L.
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<strong>Genetic complementation analysis of mitochondrial 2-methylacetoacetyl-CoA thiolase deficiency in cultured fibroblasts.</strong>
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[PubMed: 1405470]
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[Full Text: https://doi.org/10.1007/BF02435976]
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Yamaguchi, S., Orii, T., Sakura, N., Miyazawa, S., Hashimoto, T.
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<strong>Defect in biosynthesis of mitochondrial acetoacetyl-coenzyme A thiolase in cultured fibroblasts from a boy with 3-ketothiolase deficiency.</strong>
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J. Clin. Invest. 81: 813-817, 1988.
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[PubMed: 2893809]
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[Full Text: https://doi.org/10.1172/JCI113388]
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Victor A. McKusick : 6/2/1986
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