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<title>
Entry
- #302060 - BARTH SYNDROME; BTHS
- OMIM
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<span class="h4">#302060</span>
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/302060"><strong>Clinical Synopsis</strong></a>
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<a href="/phenotypicSeries/PS250950"> <strong>Phenotypic Series</strong> </a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#diagnosis">Diagnosis</a>
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<a href="#clinicalManagement">Clinical Management</a>
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<a href="#nomenclature">Nomenclature</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#pathogenesis">Pathogenesis</a>
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<a href="#genotypePhenotypeCorrelations">Genotype/Phenotype Correlations</a>
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<a href="#seeAlso"><strong>See Also</strong></a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=BARTH SYNDROME" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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&nbsp;
<div style="display: table-cell;">Animal Models</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.alliancegenome.org/disease/DOID:0050476" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
<div><a href="http://www.informatics.jax.org/disease/302060" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
<div><a href="https://omia.org/OMIA000162/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
<div><a href="https://wormbase.org/resources/disease/DOID:0050476" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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<div style="display: table-cell;">Cell Lines</div>
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<div class="panel-body small mim-panel-body">
<div><a href="https://catalog.coriell.org/Search?q=OmimNum:302060" class="definition" title="Coriell Cell Repositories; cell cultures and DNA derived from cell cultures." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'CCR', 'domain': 'ccr.coriell.org'})">Coriell</a></div>
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<span>
<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 class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>SNOMEDCT:</strong> 297231002<br />
<strong>ICD10CM:</strong> E78.71<br />
<strong>ORPHA:</strong> 111<br />
<strong>DO:</strong> 0050476<br />
">ICD+</a>
</div>
<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
302060
</span>
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<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
BARTH SYNDROME; BTHS
</span>
</h3>
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<div>
<br />
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<a id="alternativeTitles" class="mim-anchor"></a>
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<p>
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<em>Alternative titles; symbols</em>
</span>
</p>
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<h4>
<span class="mim-font">
CARDIOSKELETAL MYOPATHY WITH NEUTROPENIA AND ABNORMAL MITOCHONDRIA<br />
3-METHYLGLUTACONIC ACIDURIA, TYPE II; MGCA2<br />
MGA, TYPE II; MGA2
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/X/861?start=-3&limit=10&highlight=861">
Xq28
</a>
</span>
</td>
<td>
<span class="mim-font">
Barth syndrome
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/302060"> 302060 </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</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">
TAFAZZIN
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300394"> 300394 </a>
</span>
</td>
</tr>
</tbody>
</table>
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</div>
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<a href="/clinicalSynopsis/302060" 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')">
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<a href="/phenotypicSeries/PS250950" class="btn btn-info" role="button"> Phenotypic Series </a>
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
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<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/302060" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/302060" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
</ul>
</div>
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- X-linked recessive <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1845977&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1845977</a>, <a href="https://bioportal.bioontology.org/search?q=C1279481&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1279481</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001419" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001419</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001419" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001419</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GROWTH </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Other </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Failure to thrive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/432788009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">432788009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/54840006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">54840006</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.41" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.41</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0015544&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015544</a>, <a href="https://bioportal.bioontology.org/search?q=C2315100&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2315100</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001508</a>]</span><br /> -
Growth retardation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/59576002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">59576002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/444896005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">444896005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151686&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151686</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001510</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001510</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Face </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Myopathic facies <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/26432009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">26432009</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0332615&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0332615</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002058" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002058</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002058" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002058</a>]</span><br /> -
Round face <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0239479&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0239479</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000311" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000311</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000311" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000311</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=2ab9bbad3c428d627c2b454902c17fa0" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Face,Round-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=2ab9bbad3c428d627c2b454902c17fa0&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Tall, broad forehead <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1857354&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1857354</a>]</span><br /> -
Full cheeks <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1866231&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1866231</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000293" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000293</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000293" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000293</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=85459d10e5df48479ec4a2ec6cfc0455" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Cheeks,Full-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=85459d10e5df48479ec4a2ec6cfc0455&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
Prominent chin <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/109504005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">109504005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22810007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22810007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M26.213" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M26.213</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/524.23" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">524.23</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0399526&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0399526</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000303" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000303</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000303" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000303</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Ears </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Large ears <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/275480001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">275480001</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0554972&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0554972</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000400" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000400</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000400" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000400</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Eyes </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Deep-set eyes <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246923005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246923005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0423224&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0423224</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000490" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000490</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000490" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000490</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=08eb099548b91270db09ad79e8e75da3" target="_blank" class="small mim-tip-eom" title="&lt;img src=&quot;https://elementsofmorphology.nih.gov/images/terms/Eye,Deeply_Set-small.jpg&quot;&gt; &lt;br/&gt;Further Information: &lt;a href=&quot;https://elementsofmorphology.nih.gov/index.cgi?tid=08eb099548b91270db09ad79e8e75da3&quot target=&quot;_blank&quot onclick=&quot;gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})&quot;&gt;Elements of Morphology&lt;/a&gt;"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> CARDIOVASCULAR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Heart </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Hypertrophic cardiomyopathy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/195020003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">195020003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/233873004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">233873004</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/45227007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">45227007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I42.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/I42.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/425.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">425.1</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/425.11" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">425.11</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551472&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551472</a>, <a href="https://bioportal.bioontology.org/search?q=C0340425&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0340425</a>, <a href="https://bioportal.bioontology.org/search?q=C0007194&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007194</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001639</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001639</a>]</span><br /> -
Cardiac arrhythmias <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/698247007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">698247007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I49.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I49.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/427.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">427.9</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/427" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">427</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0003811&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0003811</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011675" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011675</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011675" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011675</a>]</span><br /> -
Endocardial fibroelastosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/65457005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">65457005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I42.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/425.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">425.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0014117&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0014117</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001706" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001706</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001706" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001706</a>]</span><br /> -
Noncompaction of left ventricle <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551005&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551005</a>]</span><br /> -
Dilated cardiomyopathy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/399020009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">399020009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/195021004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">195021004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I42.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0007193&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007193</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001644" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001644</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001644" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001644</a>]</span><br /> -
Congestive heart failure <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/42343007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">42343007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I50.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I50.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/428.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">428.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018802&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018802</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001635" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001635</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001635" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001635</a>]</span><br /> -
Ultrastructural abnormalities in mitochondria on electron microscopy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1844910&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1844910</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> SKELETAL </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Feet </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Talipes equinovarus (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/397932003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">397932003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1156475005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1156475005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q66.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q66.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q66.89" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q66.89</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/754.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">754.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0009081&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009081</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001762" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001762</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001762" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001762</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MUSCLE, SOFT TISSUES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Proximal weakness <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0750403&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0750403</a>]</span><br /> -
Fatigue <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248274002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248274002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/84229001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">84229001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R53.83" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R53.83</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0015672&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0015672</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012378" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012378</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012378" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012378</a>]</span><br /> -
Exercise intolerance <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/267044007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">267044007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0424551&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424551</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003546" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003546</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003546" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003546</a>]</span><br /> -
Abnormal gait <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22325002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22325002</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/781.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">781.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0575081&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0575081</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001288" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001288</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001288" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001288</a>]</span><br /> -
Skeletal myopathy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/75047002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">75047002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1533847&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1533847</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003756" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003756</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003756" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003756</a>]</span><br />
</span>
</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">
- Delayed motor milestones <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1854301&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1854301</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001270" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001270</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001270" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001270</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> VOICE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Nasal quality to speech <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551006&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551006</a>]</span><br />
</span>
</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">
- Intermittent lactic acidemia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1844917&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1844917</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004913" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004913</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004913" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004913</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEMATOLOGY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Neutropenia (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/303011007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">303011007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/165517008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">165517008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/84828003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">84828003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D70" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D70</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/D72.819" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D72.819</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/D70.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D70.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/288.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">288.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/288.50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">288.50</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/288.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">288.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0853697&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0853697</a>, <a href="https://bioportal.bioontology.org/search?q=C0027947&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027947</a>, <a href="https://bioportal.bioontology.org/search?q=C0023530&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023530</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001875" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001875</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001882" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001882</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001875" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001875</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> IMMUNOLOGY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Recurrent infections in infancy and early childhood <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1844909&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1844909</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005437" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005437</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005437" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005437</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> PRENATAL MANIFESTATIONS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Fetal demise, male <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3806750&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3806750</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">
- Organic aciduria, mild (in some patients) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551003&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551003</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001992" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001992</a>]</span><br /> -
Elevated urinary 3-methylglutaconate <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1844912&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1844912</a>]</span><br /> -
Elevated urinary 3-methylglutarate <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1844913&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1844913</a>]</span><br /> -
Elevated urinary 2-ethylhydracrylate <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1844914&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1844914</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">
- Striking intrafamilial variability<br /> -
Neuromuscular, cardiovascular, and infectious symptoms improve with age<br /> -
Dramatic late catch-up growth occurs in adolescence<br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Caused by mutation in the tafazzin gene (TAZ, <a href="/entry/300394#0001">300394.0001</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<h5>
3-Methylglutaconic aciduria
- <a href="/phenotypicSeries/PS250950">PS250950</a>
- 9 Entries
</h5>
</div>
</div>
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
<table class="table table-bordered table-condensed table-hover mim-table-padding">
<thead>
<tr>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Location</strong>
</th>
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
<strong>Phenotype</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Inheritance</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />mapping key</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />MIM number</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Gene/Locus<br />MIM number</strong>
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/2/389?start=-3&limit=10&highlight=389"> 2p13.1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617248"> 3-methylglutaconic aciduria, type VIII </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">
<a href="/entry/617248"> 617248 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606441"> HTRA2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606441"> 606441 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/3/888?start=-3&limit=10&highlight=888"> 3q26.33 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/610198"> 3-methylglutaconic aciduria, type V </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">
<a href="/entry/610198"> 610198 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608977"> DNAJC19 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/608977"> 608977 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/6/982?start=-3&limit=10&highlight=982"> 6q25.3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614739"> 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome </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">
<a href="/entry/614739"> 614739 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614725"> SERAC1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/614725"> 614725 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/9/298?start=-3&limit=10&highlight=298"> 9q22.31 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/250950"> 3-methylglutaconic aciduria, type I </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">
<a href="/entry/250950"> 250950 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600529"> AUH </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/600529"> 600529 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/11/722?start=-3&limit=10&highlight=722"> 11q13.4 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616271"> 3-methylglutaconic aciduria, type VIIB, autosomal recessive </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">
<a href="/entry/616271"> 616271 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616254"> CLPB </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/616254"> 616254 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/684?start=-3&limit=10&highlight=684"> 19q13.2 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/617698"> 3-methylglutaconic aciduria, type IX </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">
<a href="/entry/617698"> 617698 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607381"> TIMM50 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607381"> 607381 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/19/826?start=-3&limit=10&highlight=826"> 19q13.32 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/258501"> 3-methylglutaconic aciduria, type III </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">
<a href="/entry/258501"> 258501 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606580"> OPA3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606580"> 606580 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/X/861?start=-3&limit=10&highlight=861"> Xq28 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/302060"> Barth syndrome </a>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="X-linked recessive">XLR</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">
<a href="/entry/302060"> 302060 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300394"> TAFAZZIN </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/300394"> 300394 </a>
</span>
</td>
</tr>
<tr>
<td>
<span class="mim-font">
Not Mapped
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/250951"> 3-methylglutaconic aciduria, type IV </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">
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/250951"> 250951 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/250951"> MGCA1 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/250951"> 250951 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
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<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
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<p>A number sign (#) is used with this entry because Barth syndrome (BTHS), also known as 3-methylglutaconic aciduria type II (MGCA2), is caused by mutation in the tafazzin gene (TAFAZZIN; <a href="/entry/300394">300394</a>) on chromosome Xq28.</p>
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<strong>Description</strong>
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<p>Barth syndrome (BTHS) is an X-linked disease conventionally characterized by dilated cardiomyopathy (CMD) with endocardial fibroelastosis (EFE), a predominantly proximal skeletal myopathy, growth retardation, neutropenia, and organic aciduria, particularly excess of 3-methylglutaconic acid. Features of the disease that are less well known include hypertrophic cardiomyopathy, isolated left ventricular noncompaction (LVNC), ventricular arrhythmia, motor delay, poor appetite, fatigue and exercise intolerance, hypoglycemia, lactic acidosis, hyperammonemia, and dramatic late catch-up growth after growth delay throughout childhood (summary by <a href="#37" class="mim-tip-reference" title="Steward, C. G., Newbury-Ecob, R. A., Hastings, R., Smithson, S. F., Tsai-Goodman, B., Quarrell, O. W., Kulik, W., Wanders, R., Pennock, M., Williams, M., Cresswell, J. L., Gonzalez, I. L., Brennan, P. &lt;strong&gt;Barth syndrome: an X-linked cause of fetal cardiomyopathy and stillbirth.&lt;/strong&gt; Prenatal Diag. 30: 970-976, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20812380/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20812380&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/pd.2599&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20812380">Steward et al., 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20812380" 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>For a phenotypic description and a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA type I (<a href="/entry/250950">250950</a>).</p>
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<strong>Clinical Features</strong>
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<p>Barth et al. (<a href="#7" class="mim-tip-reference" title="Barth, P. G., Van&#x27;t Veer-Korthof, E. T., Van Delden, L., Van Dam, K., Van der Harten, J. J., Kuipers, J. R. G. &lt;strong&gt;An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leukocytes. In: Busch, H. F. M.; Jennekens, F. G. I.; Schotte, H. R. (eds.): Mitochondria and Muscular Diseases.&lt;/strong&gt; Beetsterzwaag, The Netherlands: Mefar (pub.) 1981. Pp. 161-164."None>1981</a>, <a href="#5" class="mim-tip-reference" title="Barth, P. G., Scholte, J. A., Berden, J. A., Van der Klei-Van Moorsel, J. M., Luyt-Houwen, I. E. M., Van&#x27;t Veer-Korthof, E. T., Van der Harten, J. J., Sobotka-Plojhar, M. A. &lt;strong&gt;An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leucocytes.&lt;/strong&gt; J. Neurol. Sci. 62: 327-355, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6142097/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6142097&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-510x(83)90209-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6142097">1983</a>) described a large Dutch pedigree showing X-linked inheritance of a disorder characterized by dilated cardiomyopathy, neutropenia, skeletal myopathy, and abnormal mitochondria. By electron microscopy, the mitochondria showed concentric, tightly packed cristae and occasional inclusion bodies. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6142097" 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="#22" class="mim-tip-reference" title="Hodgson, S., Child, A., Dyson, M. &lt;strong&gt;Endocardial fibroelastosis: possible X linked inheritance.&lt;/strong&gt; J. Med. Genet. 24: 210-214, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3585935/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3585935&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.24.4.210&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3585935">Hodgson et al. (1987)</a> thought that the same disorder was present in the family they reported in which many males in at least 3 generations and 7 sibships connected through females died between ages 3 days and 31 months of sepsis due to agranulocytosis or of cardiac failure. Weakness of skeletal muscles with sparing of the extraocular and bulbar muscles was noted. Granulocytopenia was found as early as cord blood samples. Differentiation in the bone marrow was arrested at the myelocyte stage. None of the boys had a gross structural cardiac abnormality. Endocardial fibroelastosis was documented in 2, and in 1 of these, electron microscopy demonstrated abnormality of mitochondria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3585935" 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="#22" class="mim-tip-reference" title="Hodgson, S., Child, A., Dyson, M. &lt;strong&gt;Endocardial fibroelastosis: possible X linked inheritance.&lt;/strong&gt; J. Med. Genet. 24: 210-214, 1987.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3585935/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3585935&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.24.4.210&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3585935">Hodgson et al. (1987)</a> also suggested that the family reported by <a href="#29" class="mim-tip-reference" title="Neustein, H. B., Lurie, P. R., Dahms, B., Takahashi, M. &lt;strong&gt;An X-linked recessive cardiomyopathy with abnormal mitochondria.&lt;/strong&gt; Pediatrics 64: 24-29, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/572031/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;572031&lt;/a&gt;]" pmid="572031">Neustein et al. (1979)</a> had the same disorder. <a href="#29" class="mim-tip-reference" title="Neustein, H. B., Lurie, P. R., Dahms, B., Takahashi, M. &lt;strong&gt;An X-linked recessive cardiomyopathy with abnormal mitochondria.&lt;/strong&gt; Pediatrics 64: 24-29, 1979.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/572031/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;572031&lt;/a&gt;]" pmid="572031">Neustein et al. (1979)</a> demonstrated abnormal mitochondria on electron microscopic examination of a transvascular endomyocardial biopsy from an infant with cardiomyopathy and chronic congestive heart failure. At autopsy, similar abnormal mitochondria were seen in skeletal muscle, liver, and kidneys. In 3 other males in 2 sibships related as first cousins or first cousins once removed, autopsy showed endocardial fibroelastosis and, by electron microscopy, abnormal mitochondria. A heterozygote showed no abnormality on skeletal muscle biopsy. No mention of neutropenia in the affected males was made. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=572031+3585935" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#23" class="mim-tip-reference" title="Ino, T., Sherwood, W. G., Cutz, E., Benson, L. N., Rose, V., Freedom, R. M. &lt;strong&gt;Dilated cardiomyopathy with neutropenia, short stature and abnormal carnitine metabolism.&lt;/strong&gt; J. Pediat. 113: 511-514, 1988.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/3411399/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;3411399&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(88)80642-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="3411399">Ino et al. (1988)</a> reported cases of dilated cardiomyopathy, short stature, and abnormal carnitine metabolism. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3411399" 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="#19" class="mim-tip-reference" title="Fixler, D. E., Cole, R. B., Paul, M. H., Lev, M., Girod, D. A. &lt;strong&gt;Familial occurrence of the contracted form of endocardial fibroelastosis.&lt;/strong&gt; Am. J. Cardiol. 26: 208-213, 1970.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5455540/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5455540&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0002-9149(70)90783-6&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="5455540">Fixler et al. (1970)</a> described 4 males in 3 sibships, related through females, with the contracted form of endocardial fibroelastosis, which is frequently associated with malformations of the heart. The affected males died of heart failure in the first years of life. <a href="#27" class="mim-tip-reference" title="Lindenbaum, R. H., Andrews, P. S., Khan, A. S. S. I. &lt;strong&gt;Two cases of endocardial fibroelastosis--possible X-linked determination.&lt;/strong&gt; Brit. Heart J. 35: 38-39, 1973.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4685904/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4685904&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/hrt.35.1.38&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4685904">Lindenbaum et al. (1973)</a> described a British kindred in which there were 2 males over 2 generations with endocardial fibroelastosis. The propositus and a male first cousin of his mother died in infancy of 'heart trouble.' Autopsies on both confirmed the primary dilated type of endocardial fibroelastosis. One had no other birth defects; the other had a hypoplastic left kidney. Several other males of this kindred died before the age of 2 years. This pattern of inheritance, along with the findings of <a href="#19" class="mim-tip-reference" title="Fixler, D. E., Cole, R. B., Paul, M. H., Lev, M., Girod, D. A. &lt;strong&gt;Familial occurrence of the contracted form of endocardial fibroelastosis.&lt;/strong&gt; Am. J. Cardiol. 26: 208-213, 1970.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5455540/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5455540&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0002-9149(70)90783-6&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="5455540">Fixler et al. (1970)</a>, suggested X-linked transmission. <a href="#41" class="mim-tip-reference" title="Westwood, M., Harris, R., Burns, J. L., Barson, A. J. &lt;strong&gt;Heredity in primary endocardial fibroelastosis.&lt;/strong&gt; Brit. Heart J. 37: 1077-1084, 1975.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/127595/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;127595&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/hrt.37.10.1077&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="127595">Westwood et al. (1975)</a> described a family with a pedigree consistent with X-linked recessive inheritance in 3 males in successive generations. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4685904+5455540+127595" 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>Kelley et al. (<a href="#26" class="mim-tip-reference" title="Kelley, R. I., Clark, B. J., Morton, D. H., Sherwood, W. G. &lt;strong&gt;X-linked cardiomyopathy, neutropenia, and increased urinary levels of 3-methylglutaconic and 2-ethylhydracrylic acids. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 45 (suppl.): A7, 1989."None>1989</a>, <a href="#25" class="mim-tip-reference" title="Kelley, R. I., Cheatham, J. P., Clark, B. J., Nigro, M. A., Powell, B. R., Sherwood, G. W., Sladky, J. T., Swisher, W. P. &lt;strong&gt;X-linked dilated cardiomyopathy with neutropenia, growth retardation, and 3-methylglutaconic aciduria.&lt;/strong&gt; J. Pediat. 119: 738-747, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1719174/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1719174&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(05)80289-6&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1719174">1991</a>) elaborated on the clinical picture of this disorder on the basis of 7 affected boys from 5 unrelated families with dilated cardiomyopathy, growth retardation, neutropenia, and persistently elevated urinary levels of 3-methylglutaconate, 3-methylglutarate, and 2-ethylhydracrylate. The clinical course of the disorder was characterized by severe or lethal cardiac disease and recurrent infections during infancy and early childhood but relative improvement in later childhood. The initial presentation of the syndrome varied from congenital dilated cardiomyopathy to infantile congestive heart failure to isolated neutropenia without clinical evidence of heart disease. The excretion of 3-methylglutaconate and 3-methylglutarate appeared to be independent of the metabolism of leucine, the presumed precursor of these organic acids. <a href="#16" class="mim-tip-reference" title="Chitayat, D., Chemke, J., Gibson, K. M., Mamer, O. A., Kronick, J. B., McGill, J. J., Rosenblatt, B., Sweetman, L., Scriver, C. R. &lt;strong&gt;3-Methylglutaconic aciduria: a marker for as yet unspecified disorders and the relevance of prenatal diagnosis in a &#x27;new&#x27; type (&#x27;type 4&#x27;).&lt;/strong&gt; J. Inherit. Metab. Dis. 15: 204-212, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1382150/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1382150&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF01799632&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1382150">Chitayat et al. (1992)</a> referred to this form of 3-methylglutaconic aciduria as type II. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1382150+1719174" 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="#33" class="mim-tip-reference" title="Orstavik, K. H., Skjorten, F., Hellebostad, M., Haga, P., Langslet, A. &lt;strong&gt;Possible X linked congenital mitochondrial cardiomyopathy in three families.&lt;/strong&gt; J. Med. Genet. 30: 269-272, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8487269/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8487269&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.30.4.269&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8487269">Orstavik et al. (1993)</a> reported 3 families with possible X-linked congestive cardiomyopathy associated with specific abnormalities of the mitochondria. The heart disorder presented as endocardial fibroelastosis with neonatal death in 2 brothers in 1 family and as heart failure and death in infancy in 2 brothers in the other 2 families. In 1 family, a maternal uncle may also have been affected. Pyoderma and neutropenia were reported in 1 of the boys. Electron microscopy of heart muscle showed increased numbers of mitochondria and abnormal mitochondrial crystal condensations and paracrystalline inclusions in all sibships. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8487269" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Ades, L. C., Gedeon, A. K., Wilson, M. J., Latham, M., Partington, M. W., Mulley, J. C., Nelson, J., Lui, K., Sillence, D. O. &lt;strong&gt;Barth syndrome: clinical features and confirmation of gene localisation to distal Xq28.&lt;/strong&gt; Am. J. Med. Genet. 45: 327-334, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8434619/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8434619&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320450309&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8434619">Ades et al. (1993)</a> studied a large Australian family with no known Dutch forebears in which affected males over 3 generations had dilated cardiomyopathy, short stature, and neutropenia. Age at diagnosis ranged from 6 weeks to 10 years, with a maximum recorded survival age of 10 years and 3 months. Clinical details were available for 6 boys, 4 deceased and 2 living. Cardiomyopathy and progressive growth failure with decline of both length and weight velocities over time were the most consistent clinical markers of disease. Some patients displayed endocardial fibroelastosis. Neutropenia was congenital and persistent in 1 boy, recurrent in 2, and documented once in another. Skeletal myopathy was present in 3 boys and was heralded by delay in gross motor development or an abnormal gait. One boy had clinical peripheral neuropathy and complex neuroophthalmologic signs, suggesting involvement of the lower midbrain and possibly the cerebellum. <a href="#3" class="mim-tip-reference" title="Ades, L. C., Gedeon, A. K., Wilson, M. J., Latham, M., Partington, M. W., Mulley, J. C., Nelson, J., Lui, K., Sillence, D. O. &lt;strong&gt;Barth syndrome: clinical features and confirmation of gene localisation to distal Xq28.&lt;/strong&gt; Am. J. Med. Genet. 45: 327-334, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8434619/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8434619&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320450309&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8434619">Ades et al. (1993)</a> noted that ophthalmoplegia is a recognized finding in mitochondrial myopathies, but had not previously been reported in patients with Barth syndrome. Additional findings included talipes equinovarus in 2 boys, 1 of whom also had minor facial anomalies and congenital pectus excavatum. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8434619" 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="Christodoulou, J., McInnes, R. R., Jay, V., Wilson, G., Becker, L. E., Lehotay, D. C., Platt, B.-A., Bridge, P. J., Robinson, B. H., Clarke, J. T. &lt;strong&gt;Barth syndrome: clinical observations and genetic linkage studies.&lt;/strong&gt; Am. J. Med. Genet. 50: 255-264, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8042670/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8042670&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320500309&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8042670">Christodoulou et al. (1994)</a> described 6 cases of Barth syndrome from 4 families, including 5 patients who were still alive at ages 11 months, 2 years, 5.9 years, 6.5 years, and 13 years. The authors noted that neuromuscular and cardiovascular symptoms and severity of infections tended to improve with age, whereas short stature persisted. In addition, they observed myopathic facies and a nasal quality to speech in their cases. Urinary organic acid abnormalities and plasma carnitine deficiency were inconsistent findings. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8042670" 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="#20" class="mim-tip-reference" title="Gedeon, A. K., Wilson, M. J., Colley, A. C., Sillence, D. O., Mulley, J. C. &lt;strong&gt;X linked fatal infantile cardiomyopathy maps to Xq28 and is possibly allelic to Barth syndrome.&lt;/strong&gt; J. Med. Genet. 32: 383-388, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7616547/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7616547&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.32.5.383&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7616547">Gedeon et al. (1995)</a> reported a large Australian family in which male infants died from congenital dilated cardiomyopathy. There was a strong family history of unexplained death in infant males over at least 4 generations in a pattern consistent with X-linked recessive inheritance. Death always occurred in early infancy, without development of the characteristic features associated with Barth syndrome, such as skeletal myopathy, short stature, and neutropenia. Two of the patients also had talipes equinovarus. Affected members of this family were originally thought to have a form of dilated cardiomyopathy, which was designated CMD3A. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7616547" 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="Bleyl, S. B., Mumford, B. R., Brown-Harrison, M.-C., Pagotto, L. T., Carey, J. C., Pysher, T. J., Ward, K., Chin, T. K. &lt;strong&gt;Xq28-linked noncompaction of the left ventricular myocardium : prenatal diagnosis and pathologic analysis of affected individuals.&lt;/strong&gt; Am. J. Med. Genet. 72: 257-265, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9332651/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9332651&lt;/a&gt;]" pmid="9332651">Bleyl et al. (1997)</a> described the clinical and pathologic findings of a 4-generation Utah family in which 6 males were affected with severe X-linked cardiomyopathy. Consistent findings included neonatal onset of ventricular dysfunction frequently complicated by arrhythmias and cardiac failure during the first year. Growth retardation was seen in 4 of the patients, neutropenia was seen in 2, and 1 patient had muscle weakness. Electrocardiographic findings were diagnostic of isolated noncompaction of the left ventricular myocardium (LVNC) (<a href="#15" class="mim-tip-reference" title="Chin, T. K., Perloff, J. K., Williams, R. G., Jue, K., Mohrmann, R. &lt;strong&gt;Isolated noncompaction of left ventricular myocardium: a study of eight cases.&lt;/strong&gt; Circulation 82: 507-513, 1990.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2372897/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2372897&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1161/01.cir.82.2.507&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2372897">Chin et al., 1990</a>). Fetal echocardiograms obtained between 24 to 30 weeks' gestation in 3 of the affected males showed a dilated left ventricle in 1, but were not otherwise diagnostic of LVNC in any of the patients. Four of the affected individuals died during infancy, 1 was in cardiac failure at age 8 months, and 1 was alive following cardiac transplant at age 9 months. The hearts from the infants who died or underwent transplantation showed dilation and hypertrophy, with coarse, deep ventricular trabeculations within the left ventricle, and prominent endocardial fibroelastosis, characteristic of LVNC. Histologically, the myocardium showed loosely arranged fascicles of myocytes, especially in the subepicardial regions and more prominent in the left ventricle. Markedly elongated mitochondria were present in some ventricular myocytes. With cardiac transplantation, a patient had survived to the age of 7 years at the time of report; with aggressive medical management, another patient was alive at age 14 months. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9332651+2372897" 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="#28" class="mim-tip-reference" title="Marziliano, N., Mannarino, S., Nespoli, L., Diegoli, M., Pasotti, M., Malattia, C., Grasso, M., Pilotto, A., Porcu, E., Raisaro, A., Raineri, C., Dore, R., Maggio, P. P., Brega, A., Arbustini, E. &lt;strong&gt;Barth syndrome associated with compound hemizygosity and heterozygosity of the TAZ and LDB3 genes.&lt;/strong&gt; Am. J. Med. Genet. 143A: 907-915, 2007.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/17394203/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;17394203&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.31653&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="17394203">Marziliano et al. (2007)</a> reported a 12-year-old boy with Barth syndrome. The boy had left ventricular noncompaction and dilated cardiomyopathy, which was detected at 3 months, skeletal myopathy, recurrent oral aphthous ulcers, and cyclic neutropenia. Left ventricular function progressively improved from age 5 years and became subclinical and normal; he presented at age 11 with recurrent ulcers and signs of myopathy, including muscle weakness and atrophy. Molecular analysis identified a mutation in the TAZ gene (<a href="/entry/300394#0012">300394.0012</a>) inherited from his unaffected mother. He was also heterozygous for a mutation in the LDB3 gene (<a href="/entry/605906">605906</a>), which is associated with left ventricular noncompaction. The patient's father and brother also carried the LDB3 mutation and had evidence of left ventricular trabeculation on imaging without dysfunction. The significance of the LDB3 mutation was unclear. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17394203" 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="#21" class="mim-tip-reference" title="Hastings, R., Steward, C., Tsai-Goodman, B., Newbury-Ecob, R. &lt;strong&gt;Dysmorphology of Barth syndrome.&lt;/strong&gt; Clin. Dysmorph. 18: 185-187, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19648820/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19648820&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1097/MCD.0b013e32832a9e62&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19648820">Hastings et al. (2009)</a> studied 12 patients from 10 families with mutation-proven Barth syndrome (see, e.g., <a href="/entry/300394#0006">300394.0006</a>) and observed similarity in the facial features of the boys. The characteristic facies was most evident in infancy and included a tall and broad forehead, round face with prominent chin and full cheeks, large ears, and deep-set eyes. The features became less evident during puberty and into adulthood, with loss of the prominence of the cheeks. The most striking feature was the development of gynoid stature and fat distribution during the late pubertal period of 'catch-up' growth. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19648820" 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="#37" class="mim-tip-reference" title="Steward, C. G., Newbury-Ecob, R. A., Hastings, R., Smithson, S. F., Tsai-Goodman, B., Quarrell, O. W., Kulik, W., Wanders, R., Pennock, M., Williams, M., Cresswell, J. L., Gonzalez, I. L., Brennan, P. &lt;strong&gt;Barth syndrome: an X-linked cause of fetal cardiomyopathy and stillbirth.&lt;/strong&gt; Prenatal Diag. 30: 970-976, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20812380/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20812380&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/pd.2599&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20812380">Steward et al. (2010)</a> reported that 6 of 19 UK families with genetically and biochemically proven Barth syndrome (see, e.g., <a href="/entry/300394#0006">300394.0006</a>) had male fetal loss and stillbirths in addition to severe neonatal illness or death. In these families, there were multiple miscarriages of male fetuses, 9 males were stillborn, and 14 males died as neonates or infants, but there were no miscarriages, stillbirths, or childhood deaths of females. BTHS was definitively proven in 5 males with fetal onset of CMD with or without hydrops, endocardial fibroelastosis, and/or left ventricular noncompaction. <a href="#37" class="mim-tip-reference" title="Steward, C. G., Newbury-Ecob, R. A., Hastings, R., Smithson, S. F., Tsai-Goodman, B., Quarrell, O. W., Kulik, W., Wanders, R., Pennock, M., Williams, M., Cresswell, J. L., Gonzalez, I. L., Brennan, P. &lt;strong&gt;Barth syndrome: an X-linked cause of fetal cardiomyopathy and stillbirth.&lt;/strong&gt; Prenatal Diag. 30: 970-976, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20812380/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20812380&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/pd.2599&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20812380">Steward et al. (2010)</a> suggested that Barth syndrome is an underrecognized cause of male fetal demise. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20812380" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#38" class="mim-tip-reference" title="Thompson, W. R., DeCroes, B., McClellan, R., Rubens, J., Vaz, F. M., Kristaponis, K., Avramopoulos, D., Vernon, H. J. &lt;strong&gt;New targets for monitoring and therapy in Barth syndrome.&lt;/strong&gt; Genet. Med 18: 1001-1010, 2016.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/26845103/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;26845103&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/gim.2015.204&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="26845103">Thompson et al. (2016)</a> conducted a multidisciplinary investigation involving 42 patients with BTHS, including echocardiograms, muscle strength testing, functional exercise capacity testing, physical activity assessments, cardiolipin analysis, 3-methylglutaconic acid analysis, and review of genotype data. Echocardiography revealed considerable variability in cardiac features. By contrast, almost all patients had significantly reduced functional exercise capacity. Multivariate analysis revealed significant relationships between cardiolipin ratio and left ventricular mass and between cardiolipin ratio and functional exercise capacity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26845103" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Baban, A., Adorisio, R., Corica, B., Rizzo, C., Cali, F., Semeraro, M., Taurisano, R., Magliozzi, M., Carrozzo, R., Parisi, F., Dallapiccola, B., Vaz, F. M., Drago, F., Dionisi-Vici, C. &lt;strong&gt;Delayed appearance of 3-methylglutaconic aciduria in neonates with early onset metabolic cardiomyopathies: a potential pitfall for the diagnosis.&lt;/strong&gt; Am. J. Med. Genet. 182A: 64-70, 2020.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/31729175/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;31729175&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.61383&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="31729175">Baban et al. (2020)</a> reported 2 children (patients 2 and 3) with Barth syndrome who did not have elevated urine 3-methylglutaconic acid when they were first tested (at 2 months of age in patient 2 and at several days of life in patient 3). However, both patients had elevated urine 3-methyglutaconic acid when retested at 6 and 18 months of age, respectively. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31729175" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Female Carriers</em></strong></p><p>
Female carriers of the BTHS gene appear to be healthy. This could be due to a selection against cells that have the mutant allele on the active X chromosome. <a href="#32" class="mim-tip-reference" title="Orstavik, K. H., Orstavik, R. E., Naumova, A. K., D&#x27;Adamo, P., Gedeon, A., Bolhuis, P. A., Barth, P. G., Toniolo, D. &lt;strong&gt;X chromosome inactivation in carriers of Barth syndrome.&lt;/strong&gt; Am. J. Hum. Genet. 63: 1457-1463, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9792874/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9792874&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/302095&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9792874">Orstavik et al. (1998)</a> therefore analyzed X-chromosome inactivation in 16 obligate carriers of BTHS from 6 families, using PCR of a polymorphic CAG repeat in the first exon of the androgen receptor gene (AR; <a href="/entry/313700">313700</a>). An extremely skewed X-inactivation pattern (equal to or more than 95:5), not found in 148 female controls, was demonstrated in 6 carriers. The skewed pattern in 2 carriers from 1 family was confirmed in DNA from cultured fibroblasts. Five carriers from 2 families had a skewed pattern, between 80:20 and less than 95:5, a pattern that was found in only 11 of 148 female controls. Of the 11 carriers with a skewed pattern, the parental origin of the inactive X chromosome was maternal in all 7 cases for which this could be determined. In 2 families, carriers with an extremely skewed pattern and carriers with a random pattern were found. The skewed X inactivation in 11 of 16 carriers is probably the result of a selection against cells with the mutated gene on the active X chromosome. Since BTHS also shows great clinical variation within families, additional factors are likely to influence the expression of the phenotype. Such factors may also influence the selection mechanism in carriers. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9792874" 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="Barth, P. &lt;strong&gt;Review of syndromes. X-linked cardioskeletal myopathy and neutropenia (MIM 302060, Barth syndrome). (Newsletter)&lt;/strong&gt; Europ. J. Paediat. Neurol. 9: 117-120, 2005."None>Barth (2005)</a> stated that no obligate or genetically proven female carriers had been reported with symptoms of the disease, and the survival of carriers did not differ from the general population.</p><p><strong><em>Reviews</em></strong></p><p>
<a href="#6" class="mim-tip-reference" title="Barth, P. G., Valianpour, F., Bowen, V. M., Lam, J., Duran, M., Vaz, F. M., Wanders, R. J. A. &lt;strong&gt;X-linked cardioskeletal myopathy and neutropenia (Barth syndrome): an update.&lt;/strong&gt; Am. J. Med. Genet. 126A: 349-354, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15098233/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15098233&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.20660&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15098233">Barth et al. (2004)</a> updated information on Barth syndrome. Following the prediction that the TAZ gene encodes one or more acyltransferases (<a href="#31" class="mim-tip-reference" title="Neuwald, A. F. &lt;strong&gt;Barth syndrome may be due to an acyltransferase deficiency.&lt;/strong&gt; Curr. Biol. 7: R465-R466, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9259571/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9259571&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0960-9822(06)00237-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9259571">Neuwald, 1997</a>), lipid studies in patients with Barth syndrome showed a deficiency of cardiolipin, especially its tetralinoleoyl form (L4-CL) (<a href="#40" class="mim-tip-reference" title="Vreken, P., Valianpour, F., Nijtmans, L. G., Grivell, L. A., Plecko, B., Wanders, R. J. A., Barth, P. G. &lt;strong&gt;Defective remodeling of cardiolipin and phosphatidylglycerol in Barth syndrome.&lt;/strong&gt; Biochem. Biophys. Res. Commun. 279: 378-382, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/11118295/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;11118295&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1006/bbrc.2000.3952&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="11118295">Vreken et al., 2000</a>). Deficiency of L4-CL was subsequently demonstrated in a variety of tissues from patients with Barth syndrome (<a href="#36" class="mim-tip-reference" title="Schlame, M., Towbin, J. A., Heerdt, P. M., Jehle, R., DiMauro, S., Blanck, T. J. J. &lt;strong&gt;Deficiency of tetralinoleoyl-cardiolipin in Barth syndrome.&lt;/strong&gt; Ann. Neurol. 51: 634-637, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12112112/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12112112&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ana.10176&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12112112">Schlame et al., 2002</a>), with determination in platelets or cultured skin fibroblasts being the most specific biochemical test. Barth syndrome was the first identified inborn error of metabolism that directly affects cardiolipin, a component of the inner mitochondrial membrane necessary for proper functioning of the electron transport chain. <a href="#6" class="mim-tip-reference" title="Barth, P. G., Valianpour, F., Bowen, V. M., Lam, J., Duran, M., Vaz, F. M., Wanders, R. J. A. &lt;strong&gt;X-linked cardioskeletal myopathy and neutropenia (Barth syndrome): an update.&lt;/strong&gt; Am. J. Med. Genet. 126A: 349-354, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15098233/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15098233&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.20660&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15098233">Barth et al. (2004)</a> found that some patients with Barth syndrome have deficient docosahexaenoic acid and arachidonic acid. They pointed out that the initial impression of a uniformly lethal infantile disorder had to be modified. Age distribution in 54 living patients ranged from neonate to 49 years and peaked around puberty. Mortality was highest in the first 4 years. An update on a family with affected members in 3 successive generations and by inference in 2 earlier generations reported by <a href="#5" class="mim-tip-reference" title="Barth, P. G., Scholte, J. A., Berden, J. A., Van der Klei-Van Moorsel, J. M., Luyt-Houwen, I. E. M., Van&#x27;t Veer-Korthof, E. T., Van der Harten, J. J., Sobotka-Plojhar, M. A. &lt;strong&gt;An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leucocytes.&lt;/strong&gt; J. Neurol. Sci. 62: 327-355, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6142097/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6142097&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-510x(83)90209-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6142097">Barth et al. (1983)</a> was provided. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=15098233+6142097+11118295+12112112+9259571" 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="Barth, P. &lt;strong&gt;Review of syndromes. X-linked cardioskeletal myopathy and neutropenia (MIM 302060, Barth syndrome). (Newsletter)&lt;/strong&gt; Europ. J. Paediat. Neurol. 9: 117-120, 2005."None>Barth (2005)</a> traced the medical history of X-linked cardioskeletal myopathy and neutropenia (Barth syndrome) to studies in the 1970s that suggested an X-linked mode of inheritance for some families with so-called endocardial fibroelastosis, a term for the pearly-white fibrotic endocardium seen at autopsy in affected individuals; this descriptive term fell into disuse when the emphasis shifted to the study of cardiac dynamics with the advent of echocardiography, with the focus on dilated cardiomyopathy. BTHS commonly presents in infancy with 1 of the following symptoms: failure to thrive, primarily due to dilated cardiomyopathy; delayed motor milestones, with proximal muscle weakness; or bacterial and/or fungal infections due to neutropenia. <a href="#8" class="mim-tip-reference" title="Barth, P. &lt;strong&gt;Review of syndromes. X-linked cardioskeletal myopathy and neutropenia (MIM 302060, Barth syndrome). (Newsletter)&lt;/strong&gt; Europ. J. Paediat. Neurol. 9: 117-120, 2005."None>Barth (2005)</a> noted that some patients reach adult age; however, there is remarkable intrafamilial variability. Cardiomyopathy and neutropenia are the main causes of high mortality, predominantly in the first 5 years of life. Proximal weakness appears to be present from birth; mild facial weakness can be observed, but there are no difficulties with swallowing, eye movements, or ventilation. There is no progression of muscle weakness and no loss of ambulation. A mild learning disability may form part of the disorder. Increased excretion of 3-methylglutaconic acid is the most characteristic biochemical marker of disease, although it is not invariably present. The neutrophil count can vary between normal and zero. Although no longer needed for diagnosis, histochemical analysis of muscle biopsy most commonly shows an increase of sarcoplasmic fat droplets on oil-red-O staining, with minimal changes to mitochondria seen on electron microscopy; heart muscle mitochondria in BTHS exhibit gross changes in shape, size, and alignment of cristae.</p>
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<p><a href="#13" class="mim-tip-reference" title="Cantlay, A. M., Shokrollahi, K., Allen, J. T., Lunt, P. W., Newbury-Ecob, R. A., Steward, C. G. &lt;strong&gt;Genetic analysis of the G4.5 gene in families with suspected Barth syndrome.&lt;/strong&gt; J. Pediat. 135: 311-315, 1999. Note: Erratum: J. Pediat. 136: 136 only, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10484795/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10484795&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(99)70126-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10484795">Cantlay et al. (1999)</a> identified 5 unrelated families within a 7-year period in 1 hospital in the area of Bristol, England, with BTHS. Mutations in the G4.5 gene were found in all of the cases (see, e.g., <a href="/entry/300394#0006">300394.0006</a>). The authors questioned whether BTHS is underdiagnosed and suggested that all male infants or young children presenting with idiopathic dilated cardiomyopathy be carefully investigated for BTHS. They noted that associated neutropenia is variable, and urinary 3-methylglutaconic acid levels fluctuate. They advocated mutation analysis, if available. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10484795" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#39" class="mim-tip-reference" title="Valianpour, F., Wanders, R. J. A., Overmars, H., Vreken, P., van Gennip, A. H., Baas, F., Plecko, B., Santer, R., Becker, K., Barth, P. G. &lt;strong&gt;Cardiolipin deficiency in X-linked cardioskeletal myopathy and neutropenia (Barth syndrome, MIM 302060): a study in cultured skin fibroblasts.&lt;/strong&gt; J. Pediat. 141: 729-733, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12410207/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12410207&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1067/mpd.2002.129174&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12410207">Valianpour et al. (2002)</a> used high performance liquid chromatography-electrospray mass spectrometry to quantify total cardiolipin and molecular subclasses in fibroblasts from 5 patients with Barth syndrome and compared the values to those in a healthy control group and a group with other diseases. Patients with Barth syndrome had decreased total cardiolipins and cardiolipin subclasses, especially tetralinoleoyl-cardiolipin. They suggested use of this biochemical test for diagnosis, followed by mutation analysis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12410207" 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="#37" class="mim-tip-reference" title="Steward, C. G., Newbury-Ecob, R. A., Hastings, R., Smithson, S. F., Tsai-Goodman, B., Quarrell, O. W., Kulik, W., Wanders, R., Pennock, M., Williams, M., Cresswell, J. L., Gonzalez, I. L., Brennan, P. &lt;strong&gt;Barth syndrome: an X-linked cause of fetal cardiomyopathy and stillbirth.&lt;/strong&gt; Prenatal Diag. 30: 970-976, 2010.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/20812380/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;20812380&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/pd.2599&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="20812380">Steward et al. (2010)</a> stated that approximately 160 unrelated cases were known to the Barth Syndrome Foundation genetic database, and noted that there were multiple barriers to case ascertainment: the relatively small increase in organic acid excretion is easily missed or may be absent; neutropenia may be intermittent or nonexistent; and a viral etiology for acute CMD is often assumed when CMD is seen in combination with neutropenia, and this misdiagnosis is compounded by the often remarkable improvement in CMD with age, seemingly confirming the suspicion that the patient has recovered from an acute viral insult. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20812380" 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="#34" class="mim-tip-reference" title="Ostman-Smith, I., Brown, G., Johnson, A., Land, J. M. &lt;strong&gt;Dilated cardiomyopathy due to type II X-linked 3-methylglutaconic aciduria: successful treatment with pantothenic acid.&lt;/strong&gt; Brit. Heart J. 72: 349-353, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7833193/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7833193&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/hrt.72.4.349&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7833193">Ostman-Smith et al. (1994)</a> described a case of type II X-linked 3-methylglutaconic aciduria in a male infant who was admitted to hospital with gross congestive heart failure at the age of 3 weeks. A metabolic cause for his dilated cardiomyopathy was suspected because of the development on the electrocardiogram of an unusual 'camel's hump' shape of the T waves and progressive thickening of the left ventricular wall with increasing echogenicity. Digitalis did not provide sustained improvement and supplementation with L-carnitine was associated with rapid deterioration in cardiac state and may be contraindicated in this condition. At a point when the patient was moribund, large doses of pantothenic acid, a precursor of coenzyme A, produced a dramatic and sustained improvement in myocardial function and in growth, neutrophil cell count, hypocholesterolemia, and hyperuricemia, which suggested that limited availability of coenzyme A was the fundamental pathologic process in this condition. After 13 months, the clinical improvement had been maintained, and myocardial function was nearly normal. Oral pantothenol, unlike pantothenic acid, was not efficacious. Since the specific enzyme defect in this disorder was then unknown, the suggested dietary treatment was entirely empirical. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7833193" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#6" class="mim-tip-reference" title="Barth, P. G., Valianpour, F., Bowen, V. M., Lam, J., Duran, M., Vaz, F. M., Wanders, R. J. A. &lt;strong&gt;X-linked cardioskeletal myopathy and neutropenia (Barth syndrome): an update.&lt;/strong&gt; Am. J. Med. Genet. 126A: 349-354, 2004.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/15098233/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;15098233&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.a.20660&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="15098233">Barth et al. (2004)</a> stated that early descriptions of Barth syndrome referred to 'X-linked endocardial fibroelastosis' (EFE) because of the shining pearly aspect of the fibrosis of the endocardium seen at autopsy. However, as methods to visualize the dynamics of the heart in vivo developed, the lack of proper contraction became the focus of attention and the descriptive terminology changed to 'dilated cardiomyopathy.' <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15098233" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>Mapping</strong>
</span>
</h4>
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<div id="mimMappingFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>By means of linkage studies in the large Dutch family reported by <a href="#5" class="mim-tip-reference" title="Barth, P. G., Scholte, J. A., Berden, J. A., Van der Klei-Van Moorsel, J. M., Luyt-Houwen, I. E. M., Van&#x27;t Veer-Korthof, E. T., Van der Harten, J. J., Sobotka-Plojhar, M. A. &lt;strong&gt;An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leucocytes.&lt;/strong&gt; J. Neurol. Sci. 62: 327-355, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6142097/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6142097&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-510x(83)90209-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6142097">Barth et al. (1983)</a>, <a href="#12" class="mim-tip-reference" title="Bolhuis, P. A., Hensels, G. W., Hulsebos, T. J. M., Baas, F., Barth, P. G. &lt;strong&gt;Mapping of the locus for X-linked cardioskeletal myopathy with neutropenia and abnormal mitochondria (Barth syndrome) to Xq28.&lt;/strong&gt; Am. J. Hum. Genet. 48: 481-485, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1998334/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1998334&lt;/a&gt;]" pmid="1998334">Bolhuis et al. (1991)</a> demonstrated that the BTHS locus is located in Xq28. Multipoint linkage analysis resulted in a maximum lod score of 5.24, with DXS305 being the closest of the markers used. <a href="#12" class="mim-tip-reference" title="Bolhuis, P. A., Hensels, G. W., Hulsebos, T. J. M., Baas, F., Barth, P. G. &lt;strong&gt;Mapping of the locus for X-linked cardioskeletal myopathy with neutropenia and abnormal mitochondria (Barth syndrome) to Xq28.&lt;/strong&gt; Am. J. Hum. Genet. 48: 481-485, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1998334/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1998334&lt;/a&gt;]" pmid="1998334">Bolhuis et al. (1991)</a> commented on the large number of genes that have been mapped to Xq28, despite its relatively small physical size, which is estimated to be 5 to 6 Mb. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1998334+6142097" 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 large Australian family in which affected males over 3 generations had dilated cardiomyopathy, short stature, and neutropenia, Ades et al. (<a href="#2" class="mim-tip-reference" title="Ades, L. C., Gedeon, A. K., Latham, M., Partington, M., Sillence, D. O., Mulley, J. C. &lt;strong&gt;Confirmation of localisation of Barth syndrome to distal Xq28. (Abstract)&lt;/strong&gt; Cytogenet. Cell Genet. 58: 2053, 1991."None>1991</a>, <a href="#3" class="mim-tip-reference" title="Ades, L. C., Gedeon, A. K., Wilson, M. J., Latham, M., Partington, M. W., Mulley, J. C., Nelson, J., Lui, K., Sillence, D. O. &lt;strong&gt;Barth syndrome: clinical features and confirmation of gene localisation to distal Xq28.&lt;/strong&gt; Am. J. Med. Genet. 45: 327-334, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8434619/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8434619&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320450309&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8434619">1993</a>) found a maximum lod score of 2.8 at theta = 0.0 with Xq28 polymorphic marker DXS52. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8434619" 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 large Australian family with X-linked dilated cardiomyopathy, <a href="#20" class="mim-tip-reference" title="Gedeon, A. K., Wilson, M. J., Colley, A. C., Sillence, D. O., Mulley, J. C. &lt;strong&gt;X linked fatal infantile cardiomyopathy maps to Xq28 and is possibly allelic to Barth syndrome.&lt;/strong&gt; J. Med. Genet. 32: 383-388, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7616547/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7616547&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.32.5.383&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7616547">Gedeon et al. (1995)</a> found linkage of the disorder to Xq28, obtaining lod scores of 2.3 at theta = 0.0 with dinucleotide repeat markers near DXS15 and at F8C (<a href="/entry/300841">300841</a>). The proximal limit of the location of the gene in this family was defined by a recombinant at DXS296, while the distal limit could not be differentiated from the telomere. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7616547" 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 4-generation Utah family in which affected males presented with ventricular dysfunction in the first year of life, associated with arrhythmias, heart failure, isolated left ventricular noncompaction, and growth retardation, <a href="#11" class="mim-tip-reference" title="Bleyl, S. B., Mumford, B. R., Thompson, V., Carey, J. C., Pysher, T. J., Chin, T. K., Ward, K. &lt;strong&gt;Neonatal, lethal noncompaction of the left ventricular myocardium is allelic with Barth syndrome.&lt;/strong&gt; Am. J. Hum. Genet. 61: 868-872, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9382097/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9382097&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/514879&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9382097">Bleyl et al. (1997)</a> found linkage to chromosome Xq28, obtaining a maximum lod score of 3.64 (theta = 0) at DXS52. Recombination events narrowed the critical region to an approximately 6.8-Mb interval distal to DSX1193. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9382097" 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>
</span>
<div>
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<div>
<a id="molecularGenetics" class="mim-anchor"></a>
<h4 href="#mimMolecularGeneticsFold" id="mimMolecularGeneticsToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
<span id="mimMolecularGeneticsToggleTriangle" class="small mimTextToggleTriangle">&#9660;</span>
<span class="mim-font">
<strong>Molecular Genetics</strong>
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</h4>
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<div id="mimMolecularGeneticsFold" class="collapse in mimTextToggleFold">
<span class="mim-text-font">
<p>In a male proband from each of 4 unrelated families with Barth syndrome, including the large Dutch pedigree originally described by Barth et al. (<a href="#7" class="mim-tip-reference" title="Barth, P. G., Van&#x27;t Veer-Korthof, E. T., Van Delden, L., Van Dam, K., Van der Harten, J. J., Kuipers, J. R. G. &lt;strong&gt;An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leukocytes. In: Busch, H. F. M.; Jennekens, F. G. I.; Schotte, H. R. (eds.): Mitochondria and Muscular Diseases.&lt;/strong&gt; Beetsterzwaag, The Netherlands: Mefar (pub.) 1981. Pp. 161-164."None>1981</a>, <a href="#5" class="mim-tip-reference" title="Barth, P. G., Scholte, J. A., Berden, J. A., Van der Klei-Van Moorsel, J. M., Luyt-Houwen, I. E. M., Van&#x27;t Veer-Korthof, E. T., Van der Harten, J. J., Sobotka-Plojhar, M. A. &lt;strong&gt;An X-linked mitochondrial disease affecting cardiac muscle, skeletal muscle and neutrophil leucocytes.&lt;/strong&gt; J. Neurol. Sci. 62: 327-355, 1983.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6142097/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6142097&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/0022-510x(83)90209-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6142097">1983</a>) and the large Australian family studied by <a href="#3" class="mim-tip-reference" title="Ades, L. C., Gedeon, A. K., Wilson, M. J., Latham, M., Partington, M. W., Mulley, J. C., Nelson, J., Lui, K., Sillence, D. O. &lt;strong&gt;Barth syndrome: clinical features and confirmation of gene localisation to distal Xq28.&lt;/strong&gt; Am. J. Med. Genet. 45: 327-334, 1993.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8434619/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8434619&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320450309&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8434619">Ades et al. (1993)</a>, <a href="#9" class="mim-tip-reference" title="Bione, S., D&#x27;Adamo, P., Maestrini, E., Gedeon, A. K., Bolhuis, P. A., Toniolo, D. &lt;strong&gt;A novel X-linked gene, G4.5.(sic) is responsible for Barth syndrome.&lt;/strong&gt; Nature Genet. 12: 385-389, 1996.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8630491/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8630491&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/ng0496-385&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8630491">Bione et al. (1996)</a> identified 4 different truncating mutations in the G4.5 gene (TAZ; <a href="/entry/300394#0001">300394.0001</a>-<a href="/entry/300394#0004">300394.0004</a>). The mutations segregated with disease in each family and were not found in the normal population. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8630491+6142097+8434619" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#18" class="mim-tip-reference" title="D&#x27;Adamo, P., Fassone, L., Gedeon, A., Janssen, E. A. M., Bione, S., Bolhuis, P. A., Barth, P. G., Wilson, M., Haan, E., Orstavik, K. H., Patton, M. A., Green, A. J., Zammarchi, E., Donati, M. A., Toniolo, D. &lt;strong&gt;The X-linked gene G4.5 is responsible for different infantile dilated cardiomyopathies.&lt;/strong&gt; Am. J. Hum. Genet. 61: 862-867, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9382096/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9382096&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/514886&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9382096">D'Adamo et al. (1997)</a> analyzed the G4.5 gene in 8 additional probands with Barth syndrome and identified mutations in 6 of them (see, e.g., <a href="/entry/300394#0006">300394.0006</a>). They also identified a 1-bp deletion (<a href="/entry/300394#0005">300394.0005</a>) in affected individuals from the large Australian family originally reported by <a href="#20" class="mim-tip-reference" title="Gedeon, A. K., Wilson, M. J., Colley, A. C., Sillence, D. O., Mulley, J. C. &lt;strong&gt;X linked fatal infantile cardiomyopathy maps to Xq28 and is possibly allelic to Barth syndrome.&lt;/strong&gt; J. Med. Genet. 32: 383-388, 1995.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7616547/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7616547&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.32.5.383&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7616547">Gedeon et al. (1995)</a> as having X-linked fatal infantile cardiomyopathy, and a missense mutation (<a href="/entry/300394#0014">300394.0014</a>) in 2 unrelated families diagnosed with endocardial fibroelastosis, 1 of which was the family previously studied by <a href="#27" class="mim-tip-reference" title="Lindenbaum, R. H., Andrews, P. S., Khan, A. S. S. I. &lt;strong&gt;Two cases of endocardial fibroelastosis--possible X-linked determination.&lt;/strong&gt; Brit. Heart J. 35: 38-39, 1973.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4685904/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4685904&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/hrt.35.1.38&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4685904">Lindenbaum et al. (1973)</a>. <a href="#18" class="mim-tip-reference" title="D&#x27;Adamo, P., Fassone, L., Gedeon, A., Janssen, E. A. M., Bione, S., Bolhuis, P. A., Barth, P. G., Wilson, M., Haan, E., Orstavik, K. H., Patton, M. A., Green, A. J., Zammarchi, E., Donati, M. A., Toniolo, D. &lt;strong&gt;The X-linked gene G4.5 is responsible for different infantile dilated cardiomyopathies.&lt;/strong&gt; Am. J. Hum. Genet. 61: 862-867, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9382096/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9382096&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/514886&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9382096">D'Adamo et al. (1997)</a> noted that the clinical data on the patients from the latter 3 families was limited and whether other features of Barth syndrome were present could not be established; they suggested that mutations in the G4.5 gene should be considered as a possible cause of infantile CMD affecting males, even in the absence of typical Barth syndrome signs. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=4685904+9382096+7616547" 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 4-generation Utah family in which affected males presented with ventricular dysfunction in the first year of life, associated with arrhythmias, heart failure, isolated left ventricular noncompaction, and growth retardation, <a href="#11" class="mim-tip-reference" title="Bleyl, S. B., Mumford, B. R., Thompson, V., Carey, J. C., Pysher, T. J., Chin, T. K., Ward, K. &lt;strong&gt;Neonatal, lethal noncompaction of the left ventricular myocardium is allelic with Barth syndrome.&lt;/strong&gt; Am. J. Hum. Genet. 61: 868-872, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9382097/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9382097&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/514879&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9382097">Bleyl et al. (1997)</a> identified a missense mutation in the G4.5 gene (G197R; <a href="/entry/300394#0006">300394.0006</a>) that segregated with disease and was not found in 300 unrelated females. Neutropenia was seen in 2 of the patients, and muscle weakness in 1. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9382097" 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="#24" class="mim-tip-reference" title="Johnston, J., Kelley, R. I., Feigenbaum, A., Cox, G. F., Iyer, G. S., Funanage, V. L., Proujansky, R. &lt;strong&gt;Mutation characterization and genotype-phenotype correlation in Barth syndrome.&lt;/strong&gt; Am. J. Hum. Genet. 61: 1053-1058, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9345098/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9345098&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/301604&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9345098">Johnston et al. (1997)</a> evaluated 14 Barth syndrome pedigrees, including the 5 pedigrees previously studied by <a href="#25" class="mim-tip-reference" title="Kelley, R. I., Cheatham, J. P., Clark, B. J., Nigro, M. A., Powell, B. R., Sherwood, G. W., Sladky, J. T., Swisher, W. P. &lt;strong&gt;X-linked dilated cardiomyopathy with neutropenia, growth retardation, and 3-methylglutaconic aciduria.&lt;/strong&gt; J. Pediat. 119: 738-747, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1719174/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1719174&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(05)80289-6&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1719174">Kelley et al. (1991)</a> and the 4 families originally reported by <a href="#17" class="mim-tip-reference" title="Christodoulou, J., McInnes, R. R., Jay, V., Wilson, G., Becker, L. E., Lehotay, D. C., Platt, B.-A., Bridge, P. J., Robinson, B. H., Clarke, J. T. &lt;strong&gt;Barth syndrome: clinical observations and genetic linkage studies.&lt;/strong&gt; Am. J. Med. Genet. 50: 255-264, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8042670/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8042670&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320500309&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8042670">Christodoulou et al. (1994)</a>, and found mutations in the G4.5 gene in all, including 5 missense mutations (see, e.g., <a href="/entry/300394#0006">300394.0006</a>), 4 splice site mutations (see, e.g., <a href="/entry/300394#0007">300394.0007</a>), 3 deletions, 1 insertion, and 1 nonsense mutation. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8042670+9345098+1719174" 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 affected individuals and obligate carriers from 5 unrelated families with Barth syndrome that presented to a hospital in Bristol, England, over a 7-year period, <a href="#13" class="mim-tip-reference" title="Cantlay, A. M., Shokrollahi, K., Allen, J. T., Lunt, P. W., Newbury-Ecob, R. A., Steward, C. G. &lt;strong&gt;Genetic analysis of the G4.5 gene in families with suspected Barth syndrome.&lt;/strong&gt; J. Pediat. 135: 311-315, 1999. Note: Erratum: J. Pediat. 136: 136 only, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10484795/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10484795&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(99)70126-5&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10484795">Cantlay et al. (1999)</a> identified mutations in the G4.5 gene (see, e.g., <a href="/entry/300394#0006">300394.0006</a>). The authors suggested that Barth syndrome may be more common than previously believed, and concluded that all young male children with idiopathic dilated cardiomyopathy should be investigated for underlying Barth syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10484795" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Chen, R., Tsuji, T., Ichida, F., Bowles, K. R., Yu, X., Watanabe, S., Hirono, K., Tsubata, S., Hamamichi, Y., Ohta, J., Imai, Y., Bowles, N. E., Miyawaki, T., Towbin, J. A., Noncompaction Study Collaborators. &lt;strong&gt;Mutation analysis of the G4.5 gene in patients with isolated left ventricular noncompaction.&lt;/strong&gt; Molec. Genet. Metab. 77: 319-325, 2002.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/12468278/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;12468278&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s1096-7192(02)00195-6&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="12468278">Chen et al. (2002)</a> analyzed the G4.5 gene in 27 Japanese patients with isolated left ventricular noncompaction, including 14 familial cases from 10 families and 13 sporadic cases, and identified a splice site mutation in 1 family (<a href="/entry/300394#0013">300394.0013</a>) that was not found in 100 Japanese or 100 Caucasian controls. The latter family had a history of unexplained male infant death, with the proband and a distant male relative presenting at 2 months and 3 months of age, respectively, with heart failure. Neither patient nor any other family members had signs of Barth syndrome such as growth retardation or skeletal myopathy. Review of the G4.5 mutations identified to date in 38 reported cases of Barth syndrome and other cardiomyopathies revealed no correlation between location or type of mutation and either cardiac phenotype or disease severity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12468278" 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="#35" class="mim-tip-reference" title="Schlame, M., Ren, M. &lt;strong&gt;Barth syndrome, a human disorder of cardiolipin metabolism.&lt;/strong&gt; FEBS Lett. 580: 5450-5455, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16973164/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16973164&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.febslet.2006.07.022&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16973164">Schlame and Ren (2006)</a> provided an overview of the molecular basis of Barth syndrome, suggesting that the acyl-specific remodeling of cardiolipin by tafazzin promotes structural uniformity and molecular symmetry among the cardiolipin molecular species, and that inhibition of this pathway leads to changes in mitochondrial architecture and function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16973164" 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 the families studied by <a href="#24" class="mim-tip-reference" title="Johnston, J., Kelley, R. I., Feigenbaum, A., Cox, G. F., Iyer, G. S., Funanage, V. L., Proujansky, R. &lt;strong&gt;Mutation characterization and genotype-phenotype correlation in Barth syndrome.&lt;/strong&gt; Am. J. Hum. Genet. 61: 1053-1058, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9345098/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9345098&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/301604&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9345098">Johnston et al. (1997)</a>, no correlation between the location or type of mutation in any of the clinical or laboratory abnormalities of Barth syndrome was found, suggesting that additional factors modify the expression of the Barth phenotype. The clinical histories of most of the subjects investigated by <a href="#24" class="mim-tip-reference" title="Johnston, J., Kelley, R. I., Feigenbaum, A., Cox, G. F., Iyer, G. S., Funanage, V. L., Proujansky, R. &lt;strong&gt;Mutation characterization and genotype-phenotype correlation in Barth syndrome.&lt;/strong&gt; Am. J. Hum. Genet. 61: 1053-1058, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9345098/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9345098&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/301604&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9345098">Johnston et al. (1997)</a> had been reported by <a href="#25" class="mim-tip-reference" title="Kelley, R. I., Cheatham, J. P., Clark, B. J., Nigro, M. A., Powell, B. R., Sherwood, G. W., Sladky, J. T., Swisher, W. P. &lt;strong&gt;X-linked dilated cardiomyopathy with neutropenia, growth retardation, and 3-methylglutaconic aciduria.&lt;/strong&gt; J. Pediat. 119: 738-747, 1991.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1719174/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1719174&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(05)80289-6&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1719174">Kelley et al. (1991)</a> or by <a href="#17" class="mim-tip-reference" title="Christodoulou, J., McInnes, R. R., Jay, V., Wilson, G., Becker, L. E., Lehotay, D. C., Platt, B.-A., Bridge, P. J., Robinson, B. H., Clarke, J. T. &lt;strong&gt;Barth syndrome: clinical observations and genetic linkage studies.&lt;/strong&gt; Am. J. Med. Genet. 50: 255-264, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/8042670/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;8042670&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1002/ajmg.1320500309&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="8042670">Christodoulou et al. (1994)</a>. The diagnosis of Barth syndrome was based on the triad of dilated cardiomyopathy, neutropenia, and increased 3-methylglutaconic aciduria in males. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=8042670+9345098+1719174" 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="#42" class="mim-tip-reference" title="Xu, Y., Condell, M., Plesken, H., Edelman-Novemsky, I., Ma, J., Ren, M., Schlame, M. &lt;strong&gt;A Drosophila model of Barth syndrome.&lt;/strong&gt; Proc. Nat. Acad. Sci. 103: 11584-11588, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16855048/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16855048&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=16855048[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.0603242103&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16855048">Xu et al. (2006)</a> generated homozygous Drosophila mutants that were unable to express full-length tafazzin and observed an 80% reduction of cardiolipin with diversification of its molecular composition, similar to the changes seen in Barth syndrome patients. Other phospholipids were not affected. Flies with the tafazzin mutation showed reduced locomotor activity, and their indirect flight muscles displayed frequent mitochondrial abnormalities, mostly in the cristae membranes. <a href="#42" class="mim-tip-reference" title="Xu, Y., Condell, M., Plesken, H., Edelman-Novemsky, I., Ma, J., Ren, M., Schlame, M. &lt;strong&gt;A Drosophila model of Barth syndrome.&lt;/strong&gt; Proc. Nat. Acad. Sci. 103: 11584-11588, 2006.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/16855048/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;16855048&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=16855048[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1073/pnas.0603242103&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="16855048">Xu et al. (2006)</a> concluded that a lack of full-length tafazzin is responsible for cardiolipin deficiency, which is integral to the disease mechanism and leads to mitochondrial myopathy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16855048" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Using RNA interference, <a href="#1" class="mim-tip-reference" title="Acehan, D., Vaz, F., Houtkooper, R. H., James, J., Moore, V., Tokunaga, C., Kulik, W., Wansapura, J., Toth, M. J., Strauss, A., Khuchua, Z. &lt;strong&gt;Cardiac and skeletal muscle defects in a mouse model of human Barth syndrome.&lt;/strong&gt; J. Biol. Chem. 286: 899-908, 2011.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/21068380/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;21068380&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=21068380[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1074/jbc.M110.171439&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="21068380">Acehan et al. (2011)</a> generated tafazzin-knockdown mice, the first mammalian model system for Barth syndrome. Tafazzin-deficient mice developed normally during the first 2 months, but at 8 months they weighed 17% less than control littermates. Tafazzin knockdown resulted in a dramatic decrease of tetralinoleoyl cardiolipin in cardiac and skeletal muscles and accumulation of monolysocardiolipins and cardiolipin molecular species with aberrant acyl groups. Electron microscopy revealed pathologic changes in mitochondria, myofibrils, and mitochondrion-associated membranes in skeletal and cardiac muscles. No overall effect was seen on the measured parameters of cardiac function at 2 months of age in tafazzin-deficient mice, but echocardiography and MRI at 8 months revealed severe cardiac abnormalities, including left ventricular dilation, left ventricular mass reduction, and depression of fractional shortening and ejection fraction. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=21068380" 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="#Neustein1979" class="mim-tip-reference" title="Neustein, H. B., Lurie, P. R., Fugita, M. &lt;strong&gt;Endocardial fibroelastosis found on transvascular endomyocardial biopsy in children.&lt;/strong&gt; Arch. Path. Lab. Med. 103: 214-219, 1979.">Neustein et al. (1979)</a>
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Acehan, D., Vaz, F., Houtkooper, R. H., James, J., Moore, V., Tokunaga, C., Kulik, W., Wansapura, J., Toth, M. J., Strauss, A., Khuchua, Z.
<strong>Cardiac and skeletal muscle defects in a mouse model of human Barth syndrome.</strong>
J. Biol. Chem. 286: 899-908, 2011.
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[<a href="https://doi.org/10.1074/jbc.M110.171439" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0022-510x(83)90209-5" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1038/ng0496-385" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1086/514879" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0022-3476(99)70126-5" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s1096-7192(02)00195-6" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1161/01.cir.82.2.507" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/ajmg.1320500309" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1086/514886" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/0002-9149(70)90783-6" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmg.32.5.383" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1097/MCD.0b013e32832a9e62" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1136/jmg.24.4.210" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1086/301604" target="_blank">Full Text</a>]
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<a id="Kelley1991" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kelley, R. I., Cheatham, J. P., Clark, B. J., Nigro, M. A., Powell, B. R., Sherwood, G. W., Sladky, J. T., Swisher, W. P.
<strong>X-linked dilated cardiomyopathy with neutropenia, growth retardation, and 3-methylglutaconic aciduria.</strong>
J. Pediat. 119: 738-747, 1991.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1719174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1719174</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1719174" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0022-3476(05)80289-6" target="_blank">Full Text</a>]
</p>
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<a id="26" class="mim-anchor"></a>
<a id="Kelley1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Kelley, R. I., Clark, B. J., Morton, D. H., Sherwood, W. G.
<strong>X-linked cardiomyopathy, neutropenia, and increased urinary levels of 3-methylglutaconic and 2-ethylhydracrylic acids. (Abstract)</strong>
Am. J. Hum. Genet. 45 (suppl.): A7, 1989.
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<a id="Lindenbaum1973" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Lindenbaum, R. H., Andrews, P. S., Khan, A. S. S. I.
<strong>Two cases of endocardial fibroelastosis--possible X-linked determination.</strong>
Brit. Heart J. 35: 38-39, 1973.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4685904/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4685904</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4685904" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/hrt.35.1.38" target="_blank">Full Text</a>]
</p>
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<a id="28" class="mim-anchor"></a>
<a id="Marziliano2007" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Marziliano, N., Mannarino, S., Nespoli, L., Diegoli, M., Pasotti, M., Malattia, C., Grasso, M., Pilotto, A., Porcu, E., Raisaro, A., Raineri, C., Dore, R., Maggio, P. P., Brega, A., Arbustini, E.
<strong>Barth syndrome associated with compound hemizygosity and heterozygosity of the TAZ and LDB3 genes.</strong>
Am. J. Med. Genet. 143A: 907-915, 2007.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17394203/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17394203</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17394203" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ajmg.a.31653" target="_blank">Full Text</a>]
</p>
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<a id="29" class="mim-anchor"></a>
<a id="Neustein1979" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Neustein, H. B., Lurie, P. R., Dahms, B., Takahashi, M.
<strong>An X-linked recessive cardiomyopathy with abnormal mitochondria.</strong>
Pediatrics 64: 24-29, 1979.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/572031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">572031</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=572031" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
</div>
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<a id="30" class="mim-anchor"></a>
<a id="Neustein1979" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Neustein, H. B., Lurie, P. R., Fugita, M.
<strong>Endocardial fibroelastosis found on transvascular endomyocardial biopsy in children.</strong>
Arch. Path. Lab. Med. 103: 214-219, 1979.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/582252/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">582252</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=582252" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
</p>
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<a id="31" class="mim-anchor"></a>
<a id="Neuwald1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Neuwald, A. F.
<strong>Barth syndrome may be due to an acyltransferase deficiency.</strong>
Curr. Biol. 7: R465-R466, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9259571/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9259571</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9259571" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0960-9822(06)00237-5" target="_blank">Full Text</a>]
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<a id="Orstavik1998" class="mim-anchor"></a>
<div class="">
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Orstavik, K. H., Orstavik, R. E., Naumova, A. K., D'Adamo, P., Gedeon, A., Bolhuis, P. A., Barth, P. G., Toniolo, D.
<strong>X chromosome inactivation in carriers of Barth syndrome.</strong>
Am. J. Hum. Genet. 63: 1457-1463, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9792874/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9792874</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9792874" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/302095" target="_blank">Full Text</a>]
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<a id="33" class="mim-anchor"></a>
<a id="Orstavik1993" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Orstavik, K. H., Skjorten, F., Hellebostad, M., Haga, P., Langslet, A.
<strong>Possible X linked congenital mitochondrial cardiomyopathy in three families.</strong>
J. Med. Genet. 30: 269-272, 1993.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/8487269/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">8487269</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=8487269" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.30.4.269" target="_blank">Full Text</a>]
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<a id="34" class="mim-anchor"></a>
<a id="Ostman-Smith1994" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Ostman-Smith, I., Brown, G., Johnson, A., Land, J. M.
<strong>Dilated cardiomyopathy due to type II X-linked 3-methylglutaconic aciduria: successful treatment with pantothenic acid.</strong>
Brit. Heart J. 72: 349-353, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7833193/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7833193</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7833193" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/hrt.72.4.349" target="_blank">Full Text</a>]
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<a id="35" class="mim-anchor"></a>
<a id="Schlame2006" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Schlame, M., Ren, M.
<strong>Barth syndrome, a human disorder of cardiolipin metabolism.</strong>
FEBS Lett. 580: 5450-5455, 2006.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/16973164/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">16973164</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=16973164" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.febslet.2006.07.022" target="_blank">Full Text</a>]
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<a id="36" class="mim-anchor"></a>
<a id="Schlame2002" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Schlame, M., Towbin, J. A., Heerdt, P. M., Jehle, R., DiMauro, S., Blanck, T. J. J.
<strong>Deficiency of tetralinoleoyl-cardiolipin in Barth syndrome.</strong>
Ann. Neurol. 51: 634-637, 2002.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12112112/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12112112</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12112112" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/ana.10176" target="_blank">Full Text</a>]
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<a id="37" class="mim-anchor"></a>
<a id="Steward2010" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Steward, C. G., Newbury-Ecob, R. A., Hastings, R., Smithson, S. F., Tsai-Goodman, B., Quarrell, O. W., Kulik, W., Wanders, R., Pennock, M., Williams, M., Cresswell, J. L., Gonzalez, I. L., Brennan, P.
<strong>Barth syndrome: an X-linked cause of fetal cardiomyopathy and stillbirth.</strong>
Prenatal Diag. 30: 970-976, 2010.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20812380/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20812380</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20812380" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1002/pd.2599" target="_blank">Full Text</a>]
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<a id="Thompson2016" class="mim-anchor"></a>
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Thompson, W. R., DeCroes, B., McClellan, R., Rubens, J., Vaz, F. M., Kristaponis, K., Avramopoulos, D., Vernon, H. J.
<strong>New targets for monitoring and therapy in Barth syndrome.</strong>
Genet. Med 18: 1001-1010, 2016.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26845103/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26845103</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26845103" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/gim.2015.204" target="_blank">Full Text</a>]
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<a id="39" class="mim-anchor"></a>
<a id="Valianpour2002" class="mim-anchor"></a>
<div class="">
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Valianpour, F., Wanders, R. J. A., Overmars, H., Vreken, P., van Gennip, A. H., Baas, F., Plecko, B., Santer, R., Becker, K., Barth, P. G.
<strong>Cardiolipin deficiency in X-linked cardioskeletal myopathy and neutropenia (Barth syndrome, MIM 302060): a study in cultured skin fibroblasts.</strong>
J. Pediat. 141: 729-733, 2002.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12410207/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12410207</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12410207" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1067/mpd.2002.129174" target="_blank">Full Text</a>]
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<a id="Vreken2000" class="mim-anchor"></a>
<div class="">
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Vreken, P., Valianpour, F., Nijtmans, L. G., Grivell, L. A., Plecko, B., Wanders, R. J. A., Barth, P. G.
<strong>Defective remodeling of cardiolipin and phosphatidylglycerol in Barth syndrome.</strong>
Biochem. Biophys. Res. Commun. 279: 378-382, 2000.
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[<a href="https://doi.org/10.1006/bbrc.2000.3952" target="_blank">Full Text</a>]
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<a id="41" class="mim-anchor"></a>
<a id="Westwood1975" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Westwood, M., Harris, R., Burns, J. L., Barson, A. J.
<strong>Heredity in primary endocardial fibroelastosis.</strong>
Brit. Heart J. 37: 1077-1084, 1975.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/127595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">127595</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=127595" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/hrt.37.10.1077" target="_blank">Full Text</a>]
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<a id="42" class="mim-anchor"></a>
<a id="Xu2006" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Xu, Y., Condell, M., Plesken, H., Edelman-Novemsky, I., Ma, J., Ren, M., Schlame, M.
<strong>A Drosophila model of Barth syndrome.</strong>
Proc. Nat. Acad. Sci. 103: 11584-11588, 2006.
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[<a href="https://doi.org/10.1073/pnas.0603242103" target="_blank">Full Text</a>]
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Hilary J. Vernon - updated : 08/24/2022
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Ada Hamosh - updated : 09/25/2018<br>Marla J. F. O'Neill - updated : 7/17/2012<br>Marla J. F. O'Neill - updated : 3/5/2010<br>Cassandra L. Kniffin - updated : 7/17/2007<br>Marla J. F. O'Neill - updated : 10/3/2006<br>Marla J. F. O'Neill - updated : 6/19/2006<br>Natalie E. Krasikov - updated : 7/14/2004<br>Victor A. McKusick - updated : 5/11/2004<br>Cassandra L. Kniffin - reorganized : 5/10/2002<br>Victor A. McKusick - updated : 1/15/2002<br>Victor A. McKusick - updated : 12/7/2001<br>Wilson H. Y. Lo - updated : 2/1/2000<br>Victor A. McKusick - updated : 10/26/1998<br>Victor A. McKusick - updated : 11/26/1997<br>Victor A. McKusick - updated : 11/11/1997<br>Victor A. McKusick - updated : 10/24/1997
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Victor A. McKusick : 4/8/1991
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<strong>#</strong> 302060
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BARTH SYNDROME; BTHS
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<em>Alternative titles; symbols</em>
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CARDIOSKELETAL MYOPATHY WITH NEUTROPENIA AND ABNORMAL MITOCHONDRIA<br />
3-METHYLGLUTACONIC ACIDURIA, TYPE II; MGCA2<br />
MGA, TYPE II; MGA2
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<strong>SNOMEDCT:</strong> 297231002; &nbsp;
<strong>ICD10CM:</strong> E78.71; &nbsp;
<strong>ORPHA:</strong> 111; &nbsp;
<strong>DO:</strong> 0050476; &nbsp;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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Xq28
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Barth syndrome
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302060
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X-linked recessive
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3
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TAFAZZIN
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300394
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because Barth syndrome (BTHS), also known as 3-methylglutaconic aciduria type II (MGCA2), is caused by mutation in the tafazzin gene (TAFAZZIN; 300394) on chromosome Xq28.</p>
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<strong>Description</strong>
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<p>Barth syndrome (BTHS) is an X-linked disease conventionally characterized by dilated cardiomyopathy (CMD) with endocardial fibroelastosis (EFE), a predominantly proximal skeletal myopathy, growth retardation, neutropenia, and organic aciduria, particularly excess of 3-methylglutaconic acid. Features of the disease that are less well known include hypertrophic cardiomyopathy, isolated left ventricular noncompaction (LVNC), ventricular arrhythmia, motor delay, poor appetite, fatigue and exercise intolerance, hypoglycemia, lactic acidosis, hyperammonemia, and dramatic late catch-up growth after growth delay throughout childhood (summary by Steward et al., 2010). </p><p>For a phenotypic description and a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA type I (250950).</p>
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<strong>Clinical Features</strong>
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<p>Barth et al. (1981, 1983) described a large Dutch pedigree showing X-linked inheritance of a disorder characterized by dilated cardiomyopathy, neutropenia, skeletal myopathy, and abnormal mitochondria. By electron microscopy, the mitochondria showed concentric, tightly packed cristae and occasional inclusion bodies. </p><p>Hodgson et al. (1987) thought that the same disorder was present in the family they reported in which many males in at least 3 generations and 7 sibships connected through females died between ages 3 days and 31 months of sepsis due to agranulocytosis or of cardiac failure. Weakness of skeletal muscles with sparing of the extraocular and bulbar muscles was noted. Granulocytopenia was found as early as cord blood samples. Differentiation in the bone marrow was arrested at the myelocyte stage. None of the boys had a gross structural cardiac abnormality. Endocardial fibroelastosis was documented in 2, and in 1 of these, electron microscopy demonstrated abnormality of mitochondria. </p><p>Hodgson et al. (1987) also suggested that the family reported by Neustein et al. (1979) had the same disorder. Neustein et al. (1979) demonstrated abnormal mitochondria on electron microscopic examination of a transvascular endomyocardial biopsy from an infant with cardiomyopathy and chronic congestive heart failure. At autopsy, similar abnormal mitochondria were seen in skeletal muscle, liver, and kidneys. In 3 other males in 2 sibships related as first cousins or first cousins once removed, autopsy showed endocardial fibroelastosis and, by electron microscopy, abnormal mitochondria. A heterozygote showed no abnormality on skeletal muscle biopsy. No mention of neutropenia in the affected males was made. </p><p>Ino et al. (1988) reported cases of dilated cardiomyopathy, short stature, and abnormal carnitine metabolism. </p><p>Fixler et al. (1970) described 4 males in 3 sibships, related through females, with the contracted form of endocardial fibroelastosis, which is frequently associated with malformations of the heart. The affected males died of heart failure in the first years of life. Lindenbaum et al. (1973) described a British kindred in which there were 2 males over 2 generations with endocardial fibroelastosis. The propositus and a male first cousin of his mother died in infancy of 'heart trouble.' Autopsies on both confirmed the primary dilated type of endocardial fibroelastosis. One had no other birth defects; the other had a hypoplastic left kidney. Several other males of this kindred died before the age of 2 years. This pattern of inheritance, along with the findings of Fixler et al. (1970), suggested X-linked transmission. Westwood et al. (1975) described a family with a pedigree consistent with X-linked recessive inheritance in 3 males in successive generations. </p><p>Kelley et al. (1989, 1991) elaborated on the clinical picture of this disorder on the basis of 7 affected boys from 5 unrelated families with dilated cardiomyopathy, growth retardation, neutropenia, and persistently elevated urinary levels of 3-methylglutaconate, 3-methylglutarate, and 2-ethylhydracrylate. The clinical course of the disorder was characterized by severe or lethal cardiac disease and recurrent infections during infancy and early childhood but relative improvement in later childhood. The initial presentation of the syndrome varied from congenital dilated cardiomyopathy to infantile congestive heart failure to isolated neutropenia without clinical evidence of heart disease. The excretion of 3-methylglutaconate and 3-methylglutarate appeared to be independent of the metabolism of leucine, the presumed precursor of these organic acids. Chitayat et al. (1992) referred to this form of 3-methylglutaconic aciduria as type II. </p><p>Orstavik et al. (1993) reported 3 families with possible X-linked congestive cardiomyopathy associated with specific abnormalities of the mitochondria. The heart disorder presented as endocardial fibroelastosis with neonatal death in 2 brothers in 1 family and as heart failure and death in infancy in 2 brothers in the other 2 families. In 1 family, a maternal uncle may also have been affected. Pyoderma and neutropenia were reported in 1 of the boys. Electron microscopy of heart muscle showed increased numbers of mitochondria and abnormal mitochondrial crystal condensations and paracrystalline inclusions in all sibships. </p><p>Ades et al. (1993) studied a large Australian family with no known Dutch forebears in which affected males over 3 generations had dilated cardiomyopathy, short stature, and neutropenia. Age at diagnosis ranged from 6 weeks to 10 years, with a maximum recorded survival age of 10 years and 3 months. Clinical details were available for 6 boys, 4 deceased and 2 living. Cardiomyopathy and progressive growth failure with decline of both length and weight velocities over time were the most consistent clinical markers of disease. Some patients displayed endocardial fibroelastosis. Neutropenia was congenital and persistent in 1 boy, recurrent in 2, and documented once in another. Skeletal myopathy was present in 3 boys and was heralded by delay in gross motor development or an abnormal gait. One boy had clinical peripheral neuropathy and complex neuroophthalmologic signs, suggesting involvement of the lower midbrain and possibly the cerebellum. Ades et al. (1993) noted that ophthalmoplegia is a recognized finding in mitochondrial myopathies, but had not previously been reported in patients with Barth syndrome. Additional findings included talipes equinovarus in 2 boys, 1 of whom also had minor facial anomalies and congenital pectus excavatum. </p><p>Christodoulou et al. (1994) described 6 cases of Barth syndrome from 4 families, including 5 patients who were still alive at ages 11 months, 2 years, 5.9 years, 6.5 years, and 13 years. The authors noted that neuromuscular and cardiovascular symptoms and severity of infections tended to improve with age, whereas short stature persisted. In addition, they observed myopathic facies and a nasal quality to speech in their cases. Urinary organic acid abnormalities and plasma carnitine deficiency were inconsistent findings. </p><p>Gedeon et al. (1995) reported a large Australian family in which male infants died from congenital dilated cardiomyopathy. There was a strong family history of unexplained death in infant males over at least 4 generations in a pattern consistent with X-linked recessive inheritance. Death always occurred in early infancy, without development of the characteristic features associated with Barth syndrome, such as skeletal myopathy, short stature, and neutropenia. Two of the patients also had talipes equinovarus. Affected members of this family were originally thought to have a form of dilated cardiomyopathy, which was designated CMD3A. </p><p>Bleyl et al. (1997) described the clinical and pathologic findings of a 4-generation Utah family in which 6 males were affected with severe X-linked cardiomyopathy. Consistent findings included neonatal onset of ventricular dysfunction frequently complicated by arrhythmias and cardiac failure during the first year. Growth retardation was seen in 4 of the patients, neutropenia was seen in 2, and 1 patient had muscle weakness. Electrocardiographic findings were diagnostic of isolated noncompaction of the left ventricular myocardium (LVNC) (Chin et al., 1990). Fetal echocardiograms obtained between 24 to 30 weeks' gestation in 3 of the affected males showed a dilated left ventricle in 1, but were not otherwise diagnostic of LVNC in any of the patients. Four of the affected individuals died during infancy, 1 was in cardiac failure at age 8 months, and 1 was alive following cardiac transplant at age 9 months. The hearts from the infants who died or underwent transplantation showed dilation and hypertrophy, with coarse, deep ventricular trabeculations within the left ventricle, and prominent endocardial fibroelastosis, characteristic of LVNC. Histologically, the myocardium showed loosely arranged fascicles of myocytes, especially in the subepicardial regions and more prominent in the left ventricle. Markedly elongated mitochondria were present in some ventricular myocytes. With cardiac transplantation, a patient had survived to the age of 7 years at the time of report; with aggressive medical management, another patient was alive at age 14 months. </p><p>Marziliano et al. (2007) reported a 12-year-old boy with Barth syndrome. The boy had left ventricular noncompaction and dilated cardiomyopathy, which was detected at 3 months, skeletal myopathy, recurrent oral aphthous ulcers, and cyclic neutropenia. Left ventricular function progressively improved from age 5 years and became subclinical and normal; he presented at age 11 with recurrent ulcers and signs of myopathy, including muscle weakness and atrophy. Molecular analysis identified a mutation in the TAZ gene (300394.0012) inherited from his unaffected mother. He was also heterozygous for a mutation in the LDB3 gene (605906), which is associated with left ventricular noncompaction. The patient's father and brother also carried the LDB3 mutation and had evidence of left ventricular trabeculation on imaging without dysfunction. The significance of the LDB3 mutation was unclear. </p><p>Hastings et al. (2009) studied 12 patients from 10 families with mutation-proven Barth syndrome (see, e.g., 300394.0006) and observed similarity in the facial features of the boys. The characteristic facies was most evident in infancy and included a tall and broad forehead, round face with prominent chin and full cheeks, large ears, and deep-set eyes. The features became less evident during puberty and into adulthood, with loss of the prominence of the cheeks. The most striking feature was the development of gynoid stature and fat distribution during the late pubertal period of 'catch-up' growth. </p><p>Steward et al. (2010) reported that 6 of 19 UK families with genetically and biochemically proven Barth syndrome (see, e.g., 300394.0006) had male fetal loss and stillbirths in addition to severe neonatal illness or death. In these families, there were multiple miscarriages of male fetuses, 9 males were stillborn, and 14 males died as neonates or infants, but there were no miscarriages, stillbirths, or childhood deaths of females. BTHS was definitively proven in 5 males with fetal onset of CMD with or without hydrops, endocardial fibroelastosis, and/or left ventricular noncompaction. Steward et al. (2010) suggested that Barth syndrome is an underrecognized cause of male fetal demise. </p><p>Thompson et al. (2016) conducted a multidisciplinary investigation involving 42 patients with BTHS, including echocardiograms, muscle strength testing, functional exercise capacity testing, physical activity assessments, cardiolipin analysis, 3-methylglutaconic acid analysis, and review of genotype data. Echocardiography revealed considerable variability in cardiac features. By contrast, almost all patients had significantly reduced functional exercise capacity. Multivariate analysis revealed significant relationships between cardiolipin ratio and left ventricular mass and between cardiolipin ratio and functional exercise capacity. </p><p>Baban et al. (2020) reported 2 children (patients 2 and 3) with Barth syndrome who did not have elevated urine 3-methylglutaconic acid when they were first tested (at 2 months of age in patient 2 and at several days of life in patient 3). However, both patients had elevated urine 3-methyglutaconic acid when retested at 6 and 18 months of age, respectively. </p><p><strong><em>Female Carriers</em></strong></p><p>
Female carriers of the BTHS gene appear to be healthy. This could be due to a selection against cells that have the mutant allele on the active X chromosome. Orstavik et al. (1998) therefore analyzed X-chromosome inactivation in 16 obligate carriers of BTHS from 6 families, using PCR of a polymorphic CAG repeat in the first exon of the androgen receptor gene (AR; 313700). An extremely skewed X-inactivation pattern (equal to or more than 95:5), not found in 148 female controls, was demonstrated in 6 carriers. The skewed pattern in 2 carriers from 1 family was confirmed in DNA from cultured fibroblasts. Five carriers from 2 families had a skewed pattern, between 80:20 and less than 95:5, a pattern that was found in only 11 of 148 female controls. Of the 11 carriers with a skewed pattern, the parental origin of the inactive X chromosome was maternal in all 7 cases for which this could be determined. In 2 families, carriers with an extremely skewed pattern and carriers with a random pattern were found. The skewed X inactivation in 11 of 16 carriers is probably the result of a selection against cells with the mutated gene on the active X chromosome. Since BTHS also shows great clinical variation within families, additional factors are likely to influence the expression of the phenotype. Such factors may also influence the selection mechanism in carriers. </p><p>Barth (2005) stated that no obligate or genetically proven female carriers had been reported with symptoms of the disease, and the survival of carriers did not differ from the general population.</p><p><strong><em>Reviews</em></strong></p><p>
Barth et al. (2004) updated information on Barth syndrome. Following the prediction that the TAZ gene encodes one or more acyltransferases (Neuwald, 1997), lipid studies in patients with Barth syndrome showed a deficiency of cardiolipin, especially its tetralinoleoyl form (L4-CL) (Vreken et al., 2000). Deficiency of L4-CL was subsequently demonstrated in a variety of tissues from patients with Barth syndrome (Schlame et al., 2002), with determination in platelets or cultured skin fibroblasts being the most specific biochemical test. Barth syndrome was the first identified inborn error of metabolism that directly affects cardiolipin, a component of the inner mitochondrial membrane necessary for proper functioning of the electron transport chain. Barth et al. (2004) found that some patients with Barth syndrome have deficient docosahexaenoic acid and arachidonic acid. They pointed out that the initial impression of a uniformly lethal infantile disorder had to be modified. Age distribution in 54 living patients ranged from neonate to 49 years and peaked around puberty. Mortality was highest in the first 4 years. An update on a family with affected members in 3 successive generations and by inference in 2 earlier generations reported by Barth et al. (1983) was provided. </p><p>Barth (2005) traced the medical history of X-linked cardioskeletal myopathy and neutropenia (Barth syndrome) to studies in the 1970s that suggested an X-linked mode of inheritance for some families with so-called endocardial fibroelastosis, a term for the pearly-white fibrotic endocardium seen at autopsy in affected individuals; this descriptive term fell into disuse when the emphasis shifted to the study of cardiac dynamics with the advent of echocardiography, with the focus on dilated cardiomyopathy. BTHS commonly presents in infancy with 1 of the following symptoms: failure to thrive, primarily due to dilated cardiomyopathy; delayed motor milestones, with proximal muscle weakness; or bacterial and/or fungal infections due to neutropenia. Barth (2005) noted that some patients reach adult age; however, there is remarkable intrafamilial variability. Cardiomyopathy and neutropenia are the main causes of high mortality, predominantly in the first 5 years of life. Proximal weakness appears to be present from birth; mild facial weakness can be observed, but there are no difficulties with swallowing, eye movements, or ventilation. There is no progression of muscle weakness and no loss of ambulation. A mild learning disability may form part of the disorder. Increased excretion of 3-methylglutaconic acid is the most characteristic biochemical marker of disease, although it is not invariably present. The neutrophil count can vary between normal and zero. Although no longer needed for diagnosis, histochemical analysis of muscle biopsy most commonly shows an increase of sarcoplasmic fat droplets on oil-red-O staining, with minimal changes to mitochondria seen on electron microscopy; heart muscle mitochondria in BTHS exhibit gross changes in shape, size, and alignment of cristae.</p>
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<strong>Diagnosis</strong>
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<p>Cantlay et al. (1999) identified 5 unrelated families within a 7-year period in 1 hospital in the area of Bristol, England, with BTHS. Mutations in the G4.5 gene were found in all of the cases (see, e.g., 300394.0006). The authors questioned whether BTHS is underdiagnosed and suggested that all male infants or young children presenting with idiopathic dilated cardiomyopathy be carefully investigated for BTHS. They noted that associated neutropenia is variable, and urinary 3-methylglutaconic acid levels fluctuate. They advocated mutation analysis, if available. </p><p>Valianpour et al. (2002) used high performance liquid chromatography-electrospray mass spectrometry to quantify total cardiolipin and molecular subclasses in fibroblasts from 5 patients with Barth syndrome and compared the values to those in a healthy control group and a group with other diseases. Patients with Barth syndrome had decreased total cardiolipins and cardiolipin subclasses, especially tetralinoleoyl-cardiolipin. They suggested use of this biochemical test for diagnosis, followed by mutation analysis. </p><p>Steward et al. (2010) stated that approximately 160 unrelated cases were known to the Barth Syndrome Foundation genetic database, and noted that there were multiple barriers to case ascertainment: the relatively small increase in organic acid excretion is easily missed or may be absent; neutropenia may be intermittent or nonexistent; and a viral etiology for acute CMD is often assumed when CMD is seen in combination with neutropenia, and this misdiagnosis is compounded by the often remarkable improvement in CMD with age, seemingly confirming the suspicion that the patient has recovered from an acute viral insult. </p>
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<strong>Clinical Management</strong>
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<p>Ostman-Smith et al. (1994) described a case of type II X-linked 3-methylglutaconic aciduria in a male infant who was admitted to hospital with gross congestive heart failure at the age of 3 weeks. A metabolic cause for his dilated cardiomyopathy was suspected because of the development on the electrocardiogram of an unusual 'camel's hump' shape of the T waves and progressive thickening of the left ventricular wall with increasing echogenicity. Digitalis did not provide sustained improvement and supplementation with L-carnitine was associated with rapid deterioration in cardiac state and may be contraindicated in this condition. At a point when the patient was moribund, large doses of pantothenic acid, a precursor of coenzyme A, produced a dramatic and sustained improvement in myocardial function and in growth, neutrophil cell count, hypocholesterolemia, and hyperuricemia, which suggested that limited availability of coenzyme A was the fundamental pathologic process in this condition. After 13 months, the clinical improvement had been maintained, and myocardial function was nearly normal. Oral pantothenol, unlike pantothenic acid, was not efficacious. Since the specific enzyme defect in this disorder was then unknown, the suggested dietary treatment was entirely empirical. </p>
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<strong>Nomenclature</strong>
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<p>Barth et al. (2004) stated that early descriptions of Barth syndrome referred to 'X-linked endocardial fibroelastosis' (EFE) because of the shining pearly aspect of the fibrosis of the endocardium seen at autopsy. However, as methods to visualize the dynamics of the heart in vivo developed, the lack of proper contraction became the focus of attention and the descriptive terminology changed to 'dilated cardiomyopathy.' </p>
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<strong>Mapping</strong>
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<p>By means of linkage studies in the large Dutch family reported by Barth et al. (1983), Bolhuis et al. (1991) demonstrated that the BTHS locus is located in Xq28. Multipoint linkage analysis resulted in a maximum lod score of 5.24, with DXS305 being the closest of the markers used. Bolhuis et al. (1991) commented on the large number of genes that have been mapped to Xq28, despite its relatively small physical size, which is estimated to be 5 to 6 Mb. </p><p>In a large Australian family in which affected males over 3 generations had dilated cardiomyopathy, short stature, and neutropenia, Ades et al. (1991, 1993) found a maximum lod score of 2.8 at theta = 0.0 with Xq28 polymorphic marker DXS52. </p><p>In a large Australian family with X-linked dilated cardiomyopathy, Gedeon et al. (1995) found linkage of the disorder to Xq28, obtaining lod scores of 2.3 at theta = 0.0 with dinucleotide repeat markers near DXS15 and at F8C (300841). The proximal limit of the location of the gene in this family was defined by a recombinant at DXS296, while the distal limit could not be differentiated from the telomere. </p><p>In a 4-generation Utah family in which affected males presented with ventricular dysfunction in the first year of life, associated with arrhythmias, heart failure, isolated left ventricular noncompaction, and growth retardation, Bleyl et al. (1997) found linkage to chromosome Xq28, obtaining a maximum lod score of 3.64 (theta = 0) at DXS52. Recombination events narrowed the critical region to an approximately 6.8-Mb interval distal to DSX1193. </p>
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<strong>Molecular Genetics</strong>
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<p>In a male proband from each of 4 unrelated families with Barth syndrome, including the large Dutch pedigree originally described by Barth et al. (1981, 1983) and the large Australian family studied by Ades et al. (1993), Bione et al. (1996) identified 4 different truncating mutations in the G4.5 gene (TAZ; 300394.0001-300394.0004). The mutations segregated with disease in each family and were not found in the normal population. </p><p>D'Adamo et al. (1997) analyzed the G4.5 gene in 8 additional probands with Barth syndrome and identified mutations in 6 of them (see, e.g., 300394.0006). They also identified a 1-bp deletion (300394.0005) in affected individuals from the large Australian family originally reported by Gedeon et al. (1995) as having X-linked fatal infantile cardiomyopathy, and a missense mutation (300394.0014) in 2 unrelated families diagnosed with endocardial fibroelastosis, 1 of which was the family previously studied by Lindenbaum et al. (1973). D'Adamo et al. (1997) noted that the clinical data on the patients from the latter 3 families was limited and whether other features of Barth syndrome were present could not be established; they suggested that mutations in the G4.5 gene should be considered as a possible cause of infantile CMD affecting males, even in the absence of typical Barth syndrome signs. </p><p>In a 4-generation Utah family in which affected males presented with ventricular dysfunction in the first year of life, associated with arrhythmias, heart failure, isolated left ventricular noncompaction, and growth retardation, Bleyl et al. (1997) identified a missense mutation in the G4.5 gene (G197R; 300394.0006) that segregated with disease and was not found in 300 unrelated females. Neutropenia was seen in 2 of the patients, and muscle weakness in 1. </p><p>Johnston et al. (1997) evaluated 14 Barth syndrome pedigrees, including the 5 pedigrees previously studied by Kelley et al. (1991) and the 4 families originally reported by Christodoulou et al. (1994), and found mutations in the G4.5 gene in all, including 5 missense mutations (see, e.g., 300394.0006), 4 splice site mutations (see, e.g., 300394.0007), 3 deletions, 1 insertion, and 1 nonsense mutation. </p><p>In affected individuals and obligate carriers from 5 unrelated families with Barth syndrome that presented to a hospital in Bristol, England, over a 7-year period, Cantlay et al. (1999) identified mutations in the G4.5 gene (see, e.g., 300394.0006). The authors suggested that Barth syndrome may be more common than previously believed, and concluded that all young male children with idiopathic dilated cardiomyopathy should be investigated for underlying Barth syndrome. </p><p>Chen et al. (2002) analyzed the G4.5 gene in 27 Japanese patients with isolated left ventricular noncompaction, including 14 familial cases from 10 families and 13 sporadic cases, and identified a splice site mutation in 1 family (300394.0013) that was not found in 100 Japanese or 100 Caucasian controls. The latter family had a history of unexplained male infant death, with the proband and a distant male relative presenting at 2 months and 3 months of age, respectively, with heart failure. Neither patient nor any other family members had signs of Barth syndrome such as growth retardation or skeletal myopathy. Review of the G4.5 mutations identified to date in 38 reported cases of Barth syndrome and other cardiomyopathies revealed no correlation between location or type of mutation and either cardiac phenotype or disease severity. </p>
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<strong>Pathogenesis</strong>
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<p>Schlame and Ren (2006) provided an overview of the molecular basis of Barth syndrome, suggesting that the acyl-specific remodeling of cardiolipin by tafazzin promotes structural uniformity and molecular symmetry among the cardiolipin molecular species, and that inhibition of this pathway leads to changes in mitochondrial architecture and function. </p>
</span>
<div>
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</div>
<div>
<h4>
<span class="mim-font">
<strong>Genotype/Phenotype Correlations</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>In the families studied by Johnston et al. (1997), no correlation between the location or type of mutation in any of the clinical or laboratory abnormalities of Barth syndrome was found, suggesting that additional factors modify the expression of the Barth phenotype. The clinical histories of most of the subjects investigated by Johnston et al. (1997) had been reported by Kelley et al. (1991) or by Christodoulou et al. (1994). The diagnosis of Barth syndrome was based on the triad of dilated cardiomyopathy, neutropenia, and increased 3-methylglutaconic aciduria in males. </p>
</span>
<div>
<br />
</div>
<div>
<h4>
<span class="mim-font">
<strong>Animal Model</strong>
</span>
</h4>
</div>
<span class="mim-text-font">
<p>Xu et al. (2006) generated homozygous Drosophila mutants that were unable to express full-length tafazzin and observed an 80% reduction of cardiolipin with diversification of its molecular composition, similar to the changes seen in Barth syndrome patients. Other phospholipids were not affected. Flies with the tafazzin mutation showed reduced locomotor activity, and their indirect flight muscles displayed frequent mitochondrial abnormalities, mostly in the cristae membranes. Xu et al. (2006) concluded that a lack of full-length tafazzin is responsible for cardiolipin deficiency, which is integral to the disease mechanism and leads to mitochondrial myopathy. </p><p>Using RNA interference, Acehan et al. (2011) generated tafazzin-knockdown mice, the first mammalian model system for Barth syndrome. Tafazzin-deficient mice developed normally during the first 2 months, but at 8 months they weighed 17% less than control littermates. Tafazzin knockdown resulted in a dramatic decrease of tetralinoleoyl cardiolipin in cardiac and skeletal muscles and accumulation of monolysocardiolipins and cardiolipin molecular species with aberrant acyl groups. Electron microscopy revealed pathologic changes in mitochondria, myofibrils, and mitochondrion-associated membranes in skeletal and cardiac muscles. No overall effect was seen on the measured parameters of cardiac function at 2 months of age in tafazzin-deficient mice, but echocardiography and MRI at 8 months revealed severe cardiac abnormalities, including left ventricular dilation, left ventricular mass reduction, and depression of fractional shortening and ejection fraction. </p>
</span>
<div>
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</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>See Also:</strong>
</span>
</h4>
<span class="mim-text-font">
Neustein et al. (1979)
</span>
<div>
<br />
</div>
</div>
<div>
<h4>
<span class="mim-font">
<strong>REFERENCES</strong>
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</h4>
<div>
<p />
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<div>
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Chen, R., Tsuji, T., Ichida, F., Bowles, K. R., Yu, X., Watanabe, S., Hirono, K., Tsubata, S., Hamamichi, Y., Ohta, J., Imai, Y., Bowles, N. E., Miyawaki, T., Towbin, J. A., Noncompaction Study Collaborators.
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Chin, T. K., Perloff, J. K., Williams, R. G., Jue, K., Mohrmann, R.
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Chitayat, D., Chemke, J., Gibson, K. M., Mamer, O. A., Kronick, J. B., McGill, J. J., Rosenblatt, B., Sweetman, L., Scriver, C. R.
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D'Adamo, P., Fassone, L., Gedeon, A., Janssen, E. A. M., Bione, S., Bolhuis, P. A., Barth, P. G., Wilson, M., Haan, E., Orstavik, K. H., Patton, M. A., Green, A. J., Zammarchi, E., Donati, M. A., Toniolo, D.
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Gedeon, A. K., Wilson, M. J., Colley, A. C., Sillence, D. O., Mulley, J. C.
<strong>X linked fatal infantile cardiomyopathy maps to Xq28 and is possibly allelic to Barth syndrome.</strong>
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Hastings, R., Steward, C., Tsai-Goodman, B., Newbury-Ecob, R.
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Hodgson, S., Child, A., Dyson, M.
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Ino, T., Sherwood, W. G., Cutz, E., Benson, L. N., Rose, V., Freedom, R. M.
<strong>Dilated cardiomyopathy with neutropenia, short stature and abnormal carnitine metabolism.</strong>
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Johnston, J., Kelley, R. I., Feigenbaum, A., Cox, G. F., Iyer, G. S., Funanage, V. L., Proujansky, R.
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Kelley, R. I., Cheatham, J. P., Clark, B. J., Nigro, M. A., Powell, B. R., Sherwood, G. W., Sladky, J. T., Swisher, W. P.
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[Full Text: https://doi.org/10.1016/s0022-3476(05)80289-6]
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Kelley, R. I., Clark, B. J., Morton, D. H., Sherwood, W. G.
<strong>X-linked cardiomyopathy, neutropenia, and increased urinary levels of 3-methylglutaconic and 2-ethylhydracrylic acids. (Abstract)</strong>
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Lindenbaum, R. H., Andrews, P. S., Khan, A. S. S. I.
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Marziliano, N., Mannarino, S., Nespoli, L., Diegoli, M., Pasotti, M., Malattia, C., Grasso, M., Pilotto, A., Porcu, E., Raisaro, A., Raineri, C., Dore, R., Maggio, P. P., Brega, A., Arbustini, E.
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Neustein, H. B., Lurie, P. R., Fugita, M.
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Neuwald, A. F.
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[PubMed: 9259571]
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</p>
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Orstavik, K. H., Orstavik, R. E., Naumova, A. K., D'Adamo, P., Gedeon, A., Bolhuis, P. A., Barth, P. G., Toniolo, D.
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Orstavik, K. H., Skjorten, F., Hellebostad, M., Haga, P., Langslet, A.
<strong>Possible X linked congenital mitochondrial cardiomyopathy in three families.</strong>
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[PubMed: 8487269]
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Ostman-Smith, I., Brown, G., Johnson, A., Land, J. M.
<strong>Dilated cardiomyopathy due to type II X-linked 3-methylglutaconic aciduria: successful treatment with pantothenic acid.</strong>
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[PubMed: 7833193]
[Full Text: https://doi.org/10.1136/hrt.72.4.349]
</p>
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<p class="mim-text-font">
Schlame, M., Ren, M.
<strong>Barth syndrome, a human disorder of cardiolipin metabolism.</strong>
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[PubMed: 16973164]
[Full Text: https://doi.org/10.1016/j.febslet.2006.07.022]
</p>
</li>
<li>
<p class="mim-text-font">
Schlame, M., Towbin, J. A., Heerdt, P. M., Jehle, R., DiMauro, S., Blanck, T. J. J.
<strong>Deficiency of tetralinoleoyl-cardiolipin in Barth syndrome.</strong>
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[PubMed: 12112112]
[Full Text: https://doi.org/10.1002/ana.10176]
</p>
</li>
<li>
<p class="mim-text-font">
Steward, C. G., Newbury-Ecob, R. A., Hastings, R., Smithson, S. F., Tsai-Goodman, B., Quarrell, O. W., Kulik, W., Wanders, R., Pennock, M., Williams, M., Cresswell, J. L., Gonzalez, I. L., Brennan, P.
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[PubMed: 20812380]
[Full Text: https://doi.org/10.1002/pd.2599]
</p>
</li>
<li>
<p class="mim-text-font">
Thompson, W. R., DeCroes, B., McClellan, R., Rubens, J., Vaz, F. M., Kristaponis, K., Avramopoulos, D., Vernon, H. J.
<strong>New targets for monitoring and therapy in Barth syndrome.</strong>
Genet. Med 18: 1001-1010, 2016.
[PubMed: 26845103]
[Full Text: https://doi.org/10.1038/gim.2015.204]
</p>
</li>
<li>
<p class="mim-text-font">
Valianpour, F., Wanders, R. J. A., Overmars, H., Vreken, P., van Gennip, A. H., Baas, F., Plecko, B., Santer, R., Becker, K., Barth, P. G.
<strong>Cardiolipin deficiency in X-linked cardioskeletal myopathy and neutropenia (Barth syndrome, MIM 302060): a study in cultured skin fibroblasts.</strong>
J. Pediat. 141: 729-733, 2002.
[PubMed: 12410207]
[Full Text: https://doi.org/10.1067/mpd.2002.129174]
</p>
</li>
<li>
<p class="mim-text-font">
Vreken, P., Valianpour, F., Nijtmans, L. G., Grivell, L. A., Plecko, B., Wanders, R. J. A., Barth, P. G.
<strong>Defective remodeling of cardiolipin and phosphatidylglycerol in Barth syndrome.</strong>
Biochem. Biophys. Res. Commun. 279: 378-382, 2000.
[PubMed: 11118295]
[Full Text: https://doi.org/10.1006/bbrc.2000.3952]
</p>
</li>
<li>
<p class="mim-text-font">
Westwood, M., Harris, R., Burns, J. L., Barson, A. J.
<strong>Heredity in primary endocardial fibroelastosis.</strong>
Brit. Heart J. 37: 1077-1084, 1975.
[PubMed: 127595]
[Full Text: https://doi.org/10.1136/hrt.37.10.1077]
</p>
</li>
<li>
<p class="mim-text-font">
Xu, Y., Condell, M., Plesken, H., Edelman-Novemsky, I., Ma, J., Ren, M., Schlame, M.
<strong>A Drosophila model of Barth syndrome.</strong>
Proc. Nat. Acad. Sci. 103: 11584-11588, 2006.
[PubMed: 16855048]
[Full Text: https://doi.org/10.1073/pnas.0603242103]
</p>
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Contributors:
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<span class="mim-text-font">
Hilary J. Vernon - updated : 08/24/2022<br>Ada Hamosh - updated : 09/25/2018<br>Marla J. F. O&#x27;Neill - updated : 7/17/2012<br>Marla J. F. O&#x27;Neill - updated : 3/5/2010<br>Cassandra L. Kniffin - updated : 7/17/2007<br>Marla J. F. O&#x27;Neill - updated : 10/3/2006<br>Marla J. F. O&#x27;Neill - updated : 6/19/2006<br>Natalie E. Krasikov - updated : 7/14/2004<br>Victor A. McKusick - updated : 5/11/2004<br>Cassandra L. Kniffin - reorganized : 5/10/2002<br>Victor A. McKusick - updated : 1/15/2002<br>Victor A. McKusick - updated : 12/7/2001<br>Wilson H. Y. Lo - updated : 2/1/2000<br>Victor A. McKusick - updated : 10/26/1998<br>Victor A. McKusick - updated : 11/26/1997<br>Victor A. McKusick - updated : 11/11/1997<br>Victor A. McKusick - updated : 10/24/1997
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<span class="text-nowrap mim-text-font">
Creation Date:
</span>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
<span class="mim-text-font">
Victor A. McKusick : 4/8/1991
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Edit History:
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