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Entry
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- #258501 - 3-METHYLGLUTACONIC ACIDURIA, TYPE III; MGCA3
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- OMIM
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<p>
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<span class="h4">#258501</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/258501"><strong>Clinical Synopsis</strong></a>
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<li role="presentation">
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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="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#mapping">Mapping</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#molecularGenetics">Molecular Genetics</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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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=3-METHYLGLUTACONIC ACIDURIA, TYPE III" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=10907&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1473/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://medlineplus.gov/genetics/condition/costeff-syndrome" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=258501[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=67047" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<div><a href="https://www.possumcore.com/nuxeo/nxdoc/default/af968122-9763-45d3-a931-3de0ac0ad790/view_documents?source=omim" class="mim-tip-hint" title="A dysmorphology database of multiple malformations; metabolic, teratogenic, chromosomal, and skeletal syndromes; and their images." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'POSSUM', 'domain': 'possum.net.au'})">POSSUM</a></div>
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</div>
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</a>
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</span>
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</span>
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</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/disease/DOID:0110004" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="http://www.informatics.jax.org/disease/258501" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0110004" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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<span 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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<a id="title" class="mim-anchor"></a>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 297232009<br />
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<strong>ORPHA:</strong> 67047<br />
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<strong>DO:</strong> 0110004<br />
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">ICD+</a>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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258501
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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3-METHYLGLUTACONIC ACIDURIA, TYPE III; MGCA3
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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MGA, TYPE III; MGA3<br />
|
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OPTIC ATROPHY PLUS SYNDROME<br />
|
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OPTIC ATROPHY, INFANTILE, WITH CHOREA AND SPASTIC PARAPLEGIA<br />
|
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IRAQI-JEWISH 'OPTIC ATROPHY PLUS'<br />
|
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COSTEFF SYNDROME<br />
|
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OPTIC ATROPHY 3, AUTOSOMAL RECESSIVE<br />
|
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OPA3, AUTOSOMAL RECESSIVE
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="phenotypeMap" class="mim-anchor"></a>
|
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<h4>
|
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<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
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</span>
|
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</h4>
|
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<div>
|
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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<tbody>
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<td>
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<span class="mim-font">
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<a href="/geneMap/19/826?start=-3&limit=10&highlight=826">
|
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19q13.32
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</a>
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</span>
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</td>
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<td>
|
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<span class="mim-font">
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3-methylglutaconic aciduria, type III
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/258501"> 258501 </a>
|
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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OPA3
|
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/606580"> 606580 </a>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/258501" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
|
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</button>
|
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</div>
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<div class="btn-group">
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|
|
<a href="/phenotypicSeries/PS250950" class="btn btn-info" role="button"> Phenotypic Series </a>
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|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
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<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
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</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/258501" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/258501" 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>
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<div>
|
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<p />
|
|
</div>
|
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|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
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<div>
|
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<div>
|
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<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
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|
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<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
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</span>
|
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</div>
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</div>
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</div>
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<div>
|
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<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
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</div>
|
|
<div style="margin-left: 2em;">
|
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<div>
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<div>
|
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<span class="h5 mim-font">
|
|
<em> Eyes </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Optic atrophy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/76976005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">76976005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.2</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.20</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/377.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.10</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/377.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0029124&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029124</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</a>]</span><br /> -
|
|
Decreased visual acuity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/13164000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">13164000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234632&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234632</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007663" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007663</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007663" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007663</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
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|
|
<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">
|
|
|
|
- Ataxia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/20262006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">20262006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/39384006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">39384006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/85102008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">85102008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R27.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R27.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.84" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.84</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0004134&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0004134</a>, <a href="https://bioportal.bioontology.org/search?q=C1135207&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1135207</a>, <a href="https://bioportal.bioontology.org/search?q=C0007758&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007758</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0010867" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010867</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>]</span><br /> -
|
|
Spasticity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/221360009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">221360009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/397790002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">397790002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026838&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026838</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001257" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001257</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001257" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001257</a>]</span><br /> -
|
|
Hyperreflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/86854008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">86854008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151889&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151889</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001347</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001347</a>]</span><br /> -
|
|
Extensor plantar responses <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246586009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246586009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/366575004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">366575004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0034935&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0034935</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003487" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003487</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003487" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003487</a>]</span><br /> -
|
|
Extrapyramidal signs <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/43378000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">43378000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234133&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234133</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002071" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002071</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002071" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002071</a>]</span><br /> -
|
|
Choreiform movements <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/271700006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">271700006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G25.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G25.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0008489&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0008489</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002072" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002072</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002072" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002072</a>]</span><br /> -
|
|
Cognitive defects (variable from mild to severe) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2678442&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2678442</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/386806002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">386806002</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0100543" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0100543</a>]</span><br /> -
|
|
Dysarthria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8011004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8011004</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.13" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.13</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/784.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">784.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span><br />
|
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|
|
</span>
|
|
</div>
|
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> LABORATORY ABNORMALITIES </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Increased urinary 3-methylglutaconic acid <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2678443&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2678443</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MISCELLANEOUS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Onset of optic atrophy in infancy or early childhood<br /> -
|
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Neurologic features occur later in childhood<br /> -
|
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Increased prevalence in individuals of Jewish-Iraqi origin<br /> -
|
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Allelic disorder to autosomal dominant optic atrophy and cataract (<a href="/entry/165300">165300</a>)<br />
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</span>
|
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MOLECULAR BASIS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Caused by mutation in the outer mitochondrial membrane lipid metabolism regulator OPA3 gene (OPA3, <a href="/entry/606580#0001">606580.0001</a>)<br />
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</span>
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</div>
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</div>
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</div>
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<div class="text-right">
|
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
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</div>
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</div>
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</div>
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<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
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<div class="small">
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<div class="row">
|
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<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
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<h5>
|
|
3-Methylglutaconic aciduria
|
|
- <a href="/phenotypicSeries/PS250950">PS250950</a>
|
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- 9 Entries
|
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</h5>
|
|
</div>
|
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</div>
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<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">
|
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<strong>Location</strong>
|
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</th>
|
|
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
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<strong>Phenotype</strong>
|
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</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
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<strong>Inheritance</strong>
|
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</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>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="text-right small">
|
|
<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
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|
|
|
|
</div>
|
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|
<div>
|
|
<br />
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<a id="text" class="mim-anchor"></a>
|
|
|
|
|
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|
|
<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
|
|
|
<span class="mim-font">
|
|
<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
|
</span>
|
|
</h4>
|
|
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|
|
<div id="mimTextFold" class="collapse in ">
|
|
<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because 3-methylglutaconic aciduria type III (MGCA3), also known as autosomal recessive optic atrophy-3 or optic atrophy plus syndrome, is caused by homozygous mutation in the OPA3 gene (<a href="/entry/606580">606580</a>) on chromosome 19q13.</p><p>See also autosomal dominant optic atrophy-3 (<a href="/entry/165300">165300</a>), an allelic disorder with a less severe phenotype.</p>
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<p>3-Methylglutaconic aciduria type III (MGCA3) is a neuroophthalmologic syndrome consisting of early-onset bilateral optic atrophy and later-onset spasticity, extrapyramidal dysfunction, and cognitive deficit. Urinary excretion of 3-methylglutaconic acid and of 3-methylglutaric acid is increased (<a href="#1" class="mim-tip-reference" title="Anikster, Y., Kleta, R., Shaag, A., Gahl, W. A., Elpeleg, O. <strong>Type III 3-methylglutaconic aciduria (optic atrophy plus syndrome, or Costeff optic atrophy syndrome): identification of the OPA3 gene and its founder mutation in Iraqi Jews.</strong> Am. J. Hum. Genet. 69: 1218-1224, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11668429/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11668429</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11668429[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/324651" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11668429">Anikster et al., 2001</a>). The phenotype is similar to Behr syndrome (<a href="/entry/210000">210000</a>) and may in some cases represent the same disorder (<a href="#11" class="mim-tip-reference" title="Sheffer, R. N., Zlotogora, J., Elpeleg, O. N., Raz, J., Ben-Ezra, D. <strong>Behr's syndrome and 3-methylglutaconic aciduria.</strong> Am. J. Ophthal. 114: 494-497, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1384336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1384336</a>] [<a href="https://doi.org/10.1016/s0002-9394(14)71864-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1384336">Sheffer et al., 1992</a>; <a href="#9" class="mim-tip-reference" title="Lerman-Sagie, T. <strong>Behr syndrome. (Letter)</strong> Pediat. Neurol. 12: 90 only, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7538304/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7538304</a>] [<a href="https://doi.org/10.1016/0887-8994(95)95022-u" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7538304">Lerman-Sagie, 1995</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1384336+7538304+11668429" 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 discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA type I (<a href="/entry/250950">250950</a>).</p>
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<p><a href="#5" class="mim-tip-reference" title="Costeff, H., Gadoth, N., Apter, N., Prialnic, M., Savir, H. <strong>A familial syndrome of infantile optic atrophy, movement disorder, and spastic paraplegia.</strong> Neurology 39: 595-597, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2494568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2494568</a>] [<a href="https://doi.org/10.1212/wnl.39.4.595" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2494568">Costeff et al. (1989)</a> described 19 patients with a familial syndrome consisting of infantile optic atrophy and an early-onset extrapyramidal movement disorder dominated by chorea. About half the patients developed spastic paraparesis during the second decade of life. Ataxia and cognitive defects were common, but usually of mild degree. Seventeen of the patients were female. Seventeen patients were distributed in 7 families. The remaining 3 were sporadic cases. Their oldest patient was 26 at the last observation and several other patients were in their twenties. The youngest patients were aged 3 years. Parental consanguinity was identified in 4 of the 10 sibships; 2 instances of first-cousin parents and 2 instances of first cousins once removed were observed. Nine of the 10 families, including all of those with multiple affected sibs, belonged to the Iraqi Jewish community in Israel, a group with an estimated minimal prevalence rate of 1:10,000. The disorder bore some similarity to Behr syndrome (<a href="/entry/210000">210000</a>) but the neurologic aspects were distinctive. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2494568" 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="Chitayat, D., Chemke, J., Gibson, K. M., Mamer, O. A., Kronick, J. B., McGill, J. J., Rosenblatt, B., Sweetman, L., Scriver, C. R. <strong>3-Methylglutaconic aciduria: a marker for as yet unspecified disorders and the relevance of prenatal diagnosis in a 'new' type ('type 4').</strong> J. Inherit. Metab. Dis. 15: 204-212, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1382150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1382150</a>] [<a href="https://doi.org/10.1007/BF01799632" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1382150">Chitayat et al. (1992)</a> alluded to the occurrence of 3-methylglutaconic aciduria in this disorder and designated the condition 3-methylglutaconic aciduria type III. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1382150" 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="#11" class="mim-tip-reference" title="Sheffer, R. N., Zlotogora, J., Elpeleg, O. N., Raz, J., Ben-Ezra, D. <strong>Behr's syndrome and 3-methylglutaconic aciduria.</strong> Am. J. Ophthal. 114: 494-497, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1384336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1384336</a>] [<a href="https://doi.org/10.1016/s0002-9394(14)71864-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1384336">Sheffer et al. (1992)</a> reported 3 patients from 2 families of Jewish Iraqi origin with early-onset optic atrophy and neurologic symptoms compatible with Behr syndrome. Neurologic signs included hyperreflexia, extensor plantar responses, spastic paraplegia, dysarthria, head nodding, and horizontal nystagmus. The patients also excreted 3-methylglutaconic acid in the urine. Inheritance was autosomal recessive. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1384336" 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="#6" class="mim-tip-reference" title="Elpeleg, O. N., Costeff, H., Joseph, A., Shental, Y., Weitz, R., Gibson, K. M. <strong>3-Methylglutaconic aciduria in the Iraqi-Jewish 'optic atrophy plus' (Costeff) syndrome.</strong> Dev. Med. Child Neurol. 36: 167-172, 1994.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7510656/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7510656</a>] [<a href="https://doi.org/10.1111/j.1469-8749.1994.tb11825.x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7510656">Elpeleg et al. (1994)</a> reported 11 new patients of Iraqi Jewish origin with the same clinical syndrome associated with 3-methylglutaconic aciduria and reviewed the clinical and biochemical findings in 36 patients. The report defined a homogeneous group of patients with type III MGCA. They differed from patients with type I MGCA by the normal 3-methylglutaconyl-CoA hydratase activity in their fibroblasts. They differed from patients with type II MGCA (<a href="/entry/302060">302060</a>) by the absence of cardiomyopathy, short stature, and neutropenia. In addition, the mode of transmission in type III is rather clearly autosomal recessive, whereas in type II it appears to be X-linked. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7510656" 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="Kleta, R., Skovby, F., Christensen, E., Rosenberg, T., Gahl, W. A., Anikster, Y. <strong>3-Methylglutaconic aciduria type III in a non-Iraqi-Jewish kindred: clinical and molecular findings.</strong> Molec. Genet. Metab. 76: 201-206, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12126933/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12126933</a>] [<a href="https://doi.org/10.1016/s1096-7192(02)00047-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12126933">Kleta et al. (2002)</a> reported a boy with type III 3-methylglutaconic aciduria who was born of consanguineous Kurdish Turkish parents. As a child, he had ataxic gait and 3-methylglutaconic aciduria. Decreased visual acuity with optic atrophy was diagnosed at age 9 years. At age 13, he was physically active with normal cognition, but had mild ataxic restlessness. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12126933" 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="#12" class="mim-tip-reference" title="Yahalom, G., Anikster, Y., Huna-Baron, R., Hoffmann, C., Blumkin, L., Lev, D., Tsabari, R., Nitsan, Z., Lerman, S. F., Ben-Zeev, B., Pode-Shakked, B., Sofer, S., Schweiger, A., Lerman-Sagie, T., Hassin-Baer, S. <strong>Costeff syndrome: clinical features and natural history.</strong> J. Neurol. 261: 2275-2282, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25201222/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25201222</a>] [<a href="https://doi.org/10.1007/s00415-014-7481-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25201222">Yahalom et al. (2014)</a> described 28 patients with MGCA3, ranging in age from 6 months to 68 years, from 21 Middle Eastern families, predominantly of Iraqi origin. Consanguinity was documented in 9 families. 3-Methylglutaconic aciduria was found in all 17 patients tested. Symptoms usually manifested in infancy or early childhood with delayed milestones. Ataxia and chorea, which were prominent features in childhood, were usually mild or moderate and did not appear to progress with age. Progressive pyramidal dysfunction presented later, leading to a high frequency of gait impairment, although most patients maintained ambulation. Dysarthria was seen in 22 patients. All 8 patients who had a neuroophthalmologic evaluation had optic atrophy, and visual acuity was severely affected in 6 of them. Of 8 patients who had MRIs, cerebellar atrophy was seen in 7, pontine atrophy in 3, and optic chiasm atrophy in 4. There was no evidence of cognitive deterioration with age. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25201222" 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="Carmi, N., Lev, D., Leshinsky-Silver, E., Anikster, Y., Blumkin, L., Kivity, S., Lerman-Sagie, T., Zerem, A. <strong>Atypical presentation of Costeff syndrome--severe psychomotor involvement and electrical status epilepticus during slow wave sleep.</strong> Europ. J. Paediat. Neurol. 19: 733-736, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26190011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26190011</a>] [<a href="https://doi.org/10.1016/j.ejpn.2015.06.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26190011">Carmi et al. (2015)</a> reported a 5-year-old girl, born to consanguineous Syrian Jewish parents, with an atypical presentation of type III MGCA. She had normal development until 7 months of age, when she developed dystonia and chorea and had regression of milestones. She also had unilateral optic atrophy, and 3-methylglutaconic aciduria was detected. At age 10 months, brain MRI and EEG were normal. Repeat urine testing did not show 3-methylglutaconic aciduria, but molecular testing confirmed MGCA3. At age 17 months, she developed focal seizures, and an EEG showed bilateral epileptic activity. At age 5 years, she had bilateral optic atrophy, choreoathetosis, and generalized hypotonia; she could not stand or walk, and had no effective speech due to severe dysarthria. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26190011" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By using a DNA pooling strategy to perform a genomewide screen followed by a high density search for shared segments among affected individuals in candidate regions identified in the initial screen, <a href="#10" class="mim-tip-reference" title="Nystuen, A., Costeff, H., Elpeleg, O. N., Apter, N., Bonne-Tamir, B., Mohrenweiser, H., Haider, N., Stone, E. M., Sheffield, V. C. <strong>Iraqi-Jewish kindreds with optic atrophy plus (3-methylglutaconic aciduria type 3) demonstrate linkage disequilibrium with the CTG repeat in the 3-prime untranslated region of the myotonic dystrophy protein kinase gene.</strong> Hum. Molec. Genet. 6: 563-569, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9097959/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9097959</a>] [<a href="https://doi.org/10.1093/hmg/6.4.563" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9097959">Nystuen et al. (1997)</a> demonstrated linkage to 19q13.2-q13.3. A lod score of 6.14 at zero recombination was obtained for the CTG repeat in the 3-prime untranslated region of the myotonic dystrophy protein kinase gene. Among the candidate genes within the 1 Mb segment which showed linkage disequilibrium was muscle type creatine kinase (CKM; <a href="/entry/123310">123310</a>). However, single-strand conformation analysis and complete sequencing of the CKM gene region showed no abnormalities in the Iraqi Jewish patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9097959" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The transmission pattern of MGCA3 in the patients reported by <a href="#1" class="mim-tip-reference" title="Anikster, Y., Kleta, R., Shaag, A., Gahl, W. A., Elpeleg, O. <strong>Type III 3-methylglutaconic aciduria (optic atrophy plus syndrome, or Costeff optic atrophy syndrome): identification of the OPA3 gene and its founder mutation in Iraqi Jews.</strong> Am. J. Hum. Genet. 69: 1218-1224, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11668429/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11668429</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11668429[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/324651" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11668429">Anikster et al. (2001)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11668429" 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="#1" class="mim-tip-reference" title="Anikster, Y., Kleta, R., Shaag, A., Gahl, W. A., Elpeleg, O. <strong>Type III 3-methylglutaconic aciduria (optic atrophy plus syndrome, or Costeff optic atrophy syndrome): identification of the OPA3 gene and its founder mutation in Iraqi Jews.</strong> Am. J. Hum. Genet. 69: 1218-1224, 2001.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11668429/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11668429</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11668429[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/324651" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11668429">Anikster et al. (2001)</a> identified a homozygous splice site mutation in the OPA3 gene (<a href="/entry/606580#0001">606580.0001</a>) in several Iraqi Jewish patients with 3-methylglutaconic aciduria type III. The authors suggested that milder mutations of OPA3 should be sought in patients with optic atrophy with later onset, even in the absence of additional neurologic abnormalities. <a href="#12" class="mim-tip-reference" title="Yahalom, G., Anikster, Y., Huna-Baron, R., Hoffmann, C., Blumkin, L., Lev, D., Tsabari, R., Nitsan, Z., Lerman, S. F., Ben-Zeev, B., Pode-Shakked, B., Sofer, S., Schweiger, A., Lerman-Sagie, T., Hassin-Baer, S. <strong>Costeff syndrome: clinical features and natural history.</strong> J. Neurol. 261: 2275-2282, 2014.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25201222/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25201222</a>] [<a href="https://doi.org/10.1007/s00415-014-7481-x" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25201222">Yahalom et al. (2014)</a> identified the same splice mutation in the OPA3 gene in 14 patients with MGCA3, all but one of whom were from Iraqi Jewish families. <a href="#3" class="mim-tip-reference" title="Carmi, N., Lev, D., Leshinsky-Silver, E., Anikster, Y., Blumkin, L., Kivity, S., Lerman-Sagie, T., Zerem, A. <strong>Atypical presentation of Costeff syndrome--severe psychomotor involvement and electrical status epilepticus during slow wave sleep.</strong> Europ. J. Paediat. Neurol. 19: 733-736, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26190011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26190011</a>] [<a href="https://doi.org/10.1016/j.ejpn.2015.06.006" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="26190011">Carmi et al. (2015)</a> identified this splice site mutation in another Iraqi Jewish patient with MGCA3. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=25201222+26190011+11668429" 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 boy, born of first-cousin Kurdish-Turkish parents, with 3-methylglutaconic aciduria type III, <a href="#8" class="mim-tip-reference" title="Kleta, R., Skovby, F., Christensen, E., Rosenberg, T., Gahl, W. A., Anikster, Y. <strong>3-Methylglutaconic aciduria type III in a non-Iraqi-Jewish kindred: clinical and molecular findings.</strong> Molec. Genet. Metab. 76: 201-206, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12126933/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12126933</a>] [<a href="https://doi.org/10.1016/s1096-7192(02)00047-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12126933">Kleta et al. (2002)</a> identified a homozygous deletion in the OPA3 gene (<a href="/entry/606580#0004">606580.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12126933" 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 an 18-year-old patient, born to nonconsanguineous Indian parents, with MGCA3, <a href="#7" class="mim-tip-reference" title="Ho, G., Walter, J. H., Christodoulou, J. <strong>Costeff optic atrophy syndrome: new clinical case and novel molecular findings.</strong> J. Inherit. Metab. Dis. 31 (Suppl. 2): S419-S423, 2008.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18985435/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18985435</a>] [<a href="https://doi.org/10.1007/s10545-008-0981-z" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="18985435">Ho et al. (2008)</a> identified a presumed homozygous nonsense mutation in exon 2 of the OPA3 gene (Q139X; 606580.0006). The unaffected father was a carrier for this mutation but DNA from the mother was not available for testing. The authors could not exclude the possibility that the patient had inherited deletion of exon 2 from the mother. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18985435" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 cousins (family DYAF09), born to consanguineous Pakistani parents, with MGCA3, <a href="#2" class="mim-tip-reference" title="Arif, B., Kumar, K. R., Seibler, P., Vulinovic, F., Fatima, A., Winkler, S., Nurnberg, G., Thiele, H., Nurnberg, P., Jamil, A. Z., Bruggemann, A., Abbas, G., Klein, C., Lohmann, K. <strong>A novel OPA3 mutation revealed by exome sequencing: an example of reverse phenotyping.</strong> JAMA Neurol. 70: 783-787, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23700088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23700088</a>] [<a href="https://doi.org/10.1001/jamaneurol.2013.1174" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23700088">Arif et al. (2013)</a> identified a homozygous missense mutation in the OPA3 gene (L11Q; <a href="/entry/606580#0005">606580.0005</a>). The mutation, which was identified by genomewide homozygosity mapping and exome sequencing, segregated with the disorder in the family. The variant was not present in the NHLBI Exome Sequencing Project database. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23700088" 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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Anikster, Y., Kleta, R., Shaag, A., Gahl, W. A., Elpeleg, O.
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<strong>Type III 3-methylglutaconic aciduria (optic atrophy plus syndrome, or Costeff optic atrophy syndrome): identification of the OPA3 gene and its founder mutation in Iraqi Jews.</strong>
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Am. J. Hum. Genet. 69: 1218-1224, 2001.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11668429/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11668429</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=11668429[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11668429" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/324651" target="_blank">Full Text</a>]
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Arif, B., Kumar, K. R., Seibler, P., Vulinovic, F., Fatima, A., Winkler, S., Nurnberg, G., Thiele, H., Nurnberg, P., Jamil, A. Z., Bruggemann, A., Abbas, G., Klein, C., Lohmann, K.
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<strong>A novel OPA3 mutation revealed by exome sequencing: an example of reverse phenotyping.</strong>
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JAMA Neurol. 70: 783-787, 2013.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23700088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23700088</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23700088" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1001/jamaneurol.2013.1174" target="_blank">Full Text</a>]
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Carmi, N., Lev, D., Leshinsky-Silver, E., Anikster, Y., Blumkin, L., Kivity, S., Lerman-Sagie, T., Zerem, A.
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<strong>Atypical presentation of Costeff syndrome--severe psychomotor involvement and electrical status epilepticus during slow wave sleep.</strong>
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Europ. J. Paediat. Neurol. 19: 733-736, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/26190011/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">26190011</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=26190011" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ejpn.2015.06.006" target="_blank">Full Text</a>]
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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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<strong>3-Methylglutaconic aciduria: a marker for as yet unspecified disorders and the relevance of prenatal diagnosis in a 'new' type ('type 4').</strong>
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J. Inherit. Metab. Dis. 15: 204-212, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1382150/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1382150</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1382150" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/BF01799632" target="_blank">Full Text</a>]
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Costeff, H., Gadoth, N., Apter, N., Prialnic, M., Savir, H.
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<strong>A familial syndrome of infantile optic atrophy, movement disorder, and spastic paraplegia.</strong>
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Neurology 39: 595-597, 1989.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2494568/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2494568</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2494568" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/wnl.39.4.595" target="_blank">Full Text</a>]
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Elpeleg, O. N., Costeff, H., Joseph, A., Shental, Y., Weitz, R., Gibson, K. M.
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<strong>3-Methylglutaconic aciduria in the Iraqi-Jewish 'optic atrophy plus' (Costeff) syndrome.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7510656/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7510656</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7510656" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/j.1469-8749.1994.tb11825.x" target="_blank">Full Text</a>]
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Ho, G., Walter, J. H., Christodoulou, J.
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<strong>Costeff optic atrophy syndrome: new clinical case and novel molecular findings.</strong>
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J. Inherit. Metab. Dis. 31 (Suppl. 2): S419-S423, 2008.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/18985435/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">18985435</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=18985435" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s10545-008-0981-z" target="_blank">Full Text</a>]
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Kleta, R., Skovby, F., Christensen, E., Rosenberg, T., Gahl, W. A., Anikster, Y.
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<strong>3-Methylglutaconic aciduria type III in a non-Iraqi-Jewish kindred: clinical and molecular findings.</strong>
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Molec. Genet. Metab. 76: 201-206, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12126933/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12126933</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12126933" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s1096-7192(02)00047-1" target="_blank">Full Text</a>]
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Lerman-Sagie, T.
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<strong>Behr syndrome. (Letter)</strong>
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Pediat. Neurol. 12: 90 only, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7538304/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7538304</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7538304" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/0887-8994(95)95022-u" target="_blank">Full Text</a>]
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Nystuen, A., Costeff, H., Elpeleg, O. N., Apter, N., Bonne-Tamir, B., Mohrenweiser, H., Haider, N., Stone, E. M., Sheffield, V. C.
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<strong>Iraqi-Jewish kindreds with optic atrophy plus (3-methylglutaconic aciduria type 3) demonstrate linkage disequilibrium with the CTG repeat in the 3-prime untranslated region of the myotonic dystrophy protein kinase gene.</strong>
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Hum. Molec. Genet. 6: 563-569, 1997.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9097959/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9097959</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9097959" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/hmg/6.4.563" target="_blank">Full Text</a>]
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<a id="Sheffer1992" class="mim-anchor"></a>
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Sheffer, R. N., Zlotogora, J., Elpeleg, O. N., Raz, J., Ben-Ezra, D.
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<strong>Behr's syndrome and 3-methylglutaconic aciduria.</strong>
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Am. J. Ophthal. 114: 494-497, 1992.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1384336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1384336</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1384336" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0002-9394(14)71864-1" target="_blank">Full Text</a>]
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<a id="Yahalom2014" class="mim-anchor"></a>
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Yahalom, G., Anikster, Y., Huna-Baron, R., Hoffmann, C., Blumkin, L., Lev, D., Tsabari, R., Nitsan, Z., Lerman, S. F., Ben-Zeev, B., Pode-Shakked, B., Sofer, S., Schweiger, A., Lerman-Sagie, T., Hassin-Baer, S.
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<strong>Costeff syndrome: clinical features and natural history.</strong>
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J. Neurol. 261: 2275-2282, 2014.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25201222/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25201222</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25201222" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1007/s00415-014-7481-x" target="_blank">Full Text</a>]
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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Hilary J. Vernon - updated : 06/16/2020
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Cassandra L. Kniffin - updated : 10/12/2007<br>Marla J. F. O'Neill - updated : 6/19/2006<br>Victor A. McKusick - updated : 12/20/2001<br>Victor A. McKusick - updated : 4/24/1997
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Victor A. McKusick : 1/5/1990
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carol : 01/31/2024
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carol : 06/18/2020<br>carol : 06/17/2020<br>carol : 06/16/2020<br>carol : 08/15/2011<br>carol : 10/18/2007<br>ckniffin : 10/12/2007<br>wwang : 6/19/2006<br>terry : 4/20/2005<br>tkritzer : 10/12/2004<br>terry : 10/12/2004<br>carol : 10/17/2002<br>carol : 12/21/2001<br>terry : 12/20/2001<br>carol : 6/8/2001<br>carol : 3/16/1999<br>dkim : 12/10/1998<br>joanna : 6/11/1997<br>alopez : 4/29/1997<br>alopez : 4/28/1997<br>alopez : 4/24/1997<br>terry : 4/23/1997<br>davew : 8/17/1994<br>carol : 4/11/1994<br>mimadm : 3/11/1994<br>carol : 7/8/1992<br>supermim : 3/17/1992<br>supermim : 3/20/1990
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<strong>#</strong> 258501
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3-METHYLGLUTACONIC ACIDURIA, TYPE III; MGCA3
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MGA, TYPE III; MGA3<br />
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OPTIC ATROPHY PLUS SYNDROME<br />
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OPTIC ATROPHY, INFANTILE, WITH CHOREA AND SPASTIC PARAPLEGIA<br />
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IRAQI-JEWISH 'OPTIC ATROPHY PLUS'<br />
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COSTEFF SYNDROME<br />
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OPTIC ATROPHY 3, AUTOSOMAL RECESSIVE<br />
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OPA3, AUTOSOMAL RECESSIVE
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<strong>SNOMEDCT:</strong> 297232009;
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<strong>ORPHA:</strong> 67047;
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<strong>DO:</strong> 0110004;
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19q13.32
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3-methylglutaconic aciduria, type III
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258501
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Autosomal recessive
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OPA3
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606580
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<p>A number sign (#) is used with this entry because 3-methylglutaconic aciduria type III (MGCA3), also known as autosomal recessive optic atrophy-3 or optic atrophy plus syndrome, is caused by homozygous mutation in the OPA3 gene (606580) on chromosome 19q13.</p><p>See also autosomal dominant optic atrophy-3 (165300), an allelic disorder with a less severe phenotype.</p>
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<p>3-Methylglutaconic aciduria type III (MGCA3) is a neuroophthalmologic syndrome consisting of early-onset bilateral optic atrophy and later-onset spasticity, extrapyramidal dysfunction, and cognitive deficit. Urinary excretion of 3-methylglutaconic acid and of 3-methylglutaric acid is increased (Anikster et al., 2001). The phenotype is similar to Behr syndrome (210000) and may in some cases represent the same disorder (Sheffer et al., 1992; Lerman-Sagie, 1995). </p><p>For a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA type I (250950).</p>
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<p>Costeff et al. (1989) described 19 patients with a familial syndrome consisting of infantile optic atrophy and an early-onset extrapyramidal movement disorder dominated by chorea. About half the patients developed spastic paraparesis during the second decade of life. Ataxia and cognitive defects were common, but usually of mild degree. Seventeen of the patients were female. Seventeen patients were distributed in 7 families. The remaining 3 were sporadic cases. Their oldest patient was 26 at the last observation and several other patients were in their twenties. The youngest patients were aged 3 years. Parental consanguinity was identified in 4 of the 10 sibships; 2 instances of first-cousin parents and 2 instances of first cousins once removed were observed. Nine of the 10 families, including all of those with multiple affected sibs, belonged to the Iraqi Jewish community in Israel, a group with an estimated minimal prevalence rate of 1:10,000. The disorder bore some similarity to Behr syndrome (210000) but the neurologic aspects were distinctive. </p><p>Chitayat et al. (1992) alluded to the occurrence of 3-methylglutaconic aciduria in this disorder and designated the condition 3-methylglutaconic aciduria type III. </p><p>Sheffer et al. (1992) reported 3 patients from 2 families of Jewish Iraqi origin with early-onset optic atrophy and neurologic symptoms compatible with Behr syndrome. Neurologic signs included hyperreflexia, extensor plantar responses, spastic paraplegia, dysarthria, head nodding, and horizontal nystagmus. The patients also excreted 3-methylglutaconic acid in the urine. Inheritance was autosomal recessive. </p><p>Elpeleg et al. (1994) reported 11 new patients of Iraqi Jewish origin with the same clinical syndrome associated with 3-methylglutaconic aciduria and reviewed the clinical and biochemical findings in 36 patients. The report defined a homogeneous group of patients with type III MGCA. They differed from patients with type I MGCA by the normal 3-methylglutaconyl-CoA hydratase activity in their fibroblasts. They differed from patients with type II MGCA (302060) by the absence of cardiomyopathy, short stature, and neutropenia. In addition, the mode of transmission in type III is rather clearly autosomal recessive, whereas in type II it appears to be X-linked. </p><p>Kleta et al. (2002) reported a boy with type III 3-methylglutaconic aciduria who was born of consanguineous Kurdish Turkish parents. As a child, he had ataxic gait and 3-methylglutaconic aciduria. Decreased visual acuity with optic atrophy was diagnosed at age 9 years. At age 13, he was physically active with normal cognition, but had mild ataxic restlessness. </p><p>Yahalom et al. (2014) described 28 patients with MGCA3, ranging in age from 6 months to 68 years, from 21 Middle Eastern families, predominantly of Iraqi origin. Consanguinity was documented in 9 families. 3-Methylglutaconic aciduria was found in all 17 patients tested. Symptoms usually manifested in infancy or early childhood with delayed milestones. Ataxia and chorea, which were prominent features in childhood, were usually mild or moderate and did not appear to progress with age. Progressive pyramidal dysfunction presented later, leading to a high frequency of gait impairment, although most patients maintained ambulation. Dysarthria was seen in 22 patients. All 8 patients who had a neuroophthalmologic evaluation had optic atrophy, and visual acuity was severely affected in 6 of them. Of 8 patients who had MRIs, cerebellar atrophy was seen in 7, pontine atrophy in 3, and optic chiasm atrophy in 4. There was no evidence of cognitive deterioration with age. </p><p>Carmi et al. (2015) reported a 5-year-old girl, born to consanguineous Syrian Jewish parents, with an atypical presentation of type III MGCA. She had normal development until 7 months of age, when she developed dystonia and chorea and had regression of milestones. She also had unilateral optic atrophy, and 3-methylglutaconic aciduria was detected. At age 10 months, brain MRI and EEG were normal. Repeat urine testing did not show 3-methylglutaconic aciduria, but molecular testing confirmed MGCA3. At age 17 months, she developed focal seizures, and an EEG showed bilateral epileptic activity. At age 5 years, she had bilateral optic atrophy, choreoathetosis, and generalized hypotonia; she could not stand or walk, and had no effective speech due to severe dysarthria. </p>
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<strong>Mapping</strong>
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<p>By using a DNA pooling strategy to perform a genomewide screen followed by a high density search for shared segments among affected individuals in candidate regions identified in the initial screen, Nystuen et al. (1997) demonstrated linkage to 19q13.2-q13.3. A lod score of 6.14 at zero recombination was obtained for the CTG repeat in the 3-prime untranslated region of the myotonic dystrophy protein kinase gene. Among the candidate genes within the 1 Mb segment which showed linkage disequilibrium was muscle type creatine kinase (CKM; 123310). However, single-strand conformation analysis and complete sequencing of the CKM gene region showed no abnormalities in the Iraqi Jewish patients. </p>
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<p>The transmission pattern of MGCA3 in the patients reported by Anikster et al. (2001) was consistent with autosomal recessive inheritance. </p>
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<strong>Molecular Genetics</strong>
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<p>Anikster et al. (2001) identified a homozygous splice site mutation in the OPA3 gene (606580.0001) in several Iraqi Jewish patients with 3-methylglutaconic aciduria type III. The authors suggested that milder mutations of OPA3 should be sought in patients with optic atrophy with later onset, even in the absence of additional neurologic abnormalities. Yahalom et al. (2014) identified the same splice mutation in the OPA3 gene in 14 patients with MGCA3, all but one of whom were from Iraqi Jewish families. Carmi et al. (2015) identified this splice site mutation in another Iraqi Jewish patient with MGCA3. </p><p>In a boy, born of first-cousin Kurdish-Turkish parents, with 3-methylglutaconic aciduria type III, Kleta et al. (2002) identified a homozygous deletion in the OPA3 gene (606580.0004). </p><p>In an 18-year-old patient, born to nonconsanguineous Indian parents, with MGCA3, Ho et al. (2008) identified a presumed homozygous nonsense mutation in exon 2 of the OPA3 gene (Q139X; 606580.0006). The unaffected father was a carrier for this mutation but DNA from the mother was not available for testing. The authors could not exclude the possibility that the patient had inherited deletion of exon 2 from the mother. </p><p>In 2 cousins (family DYAF09), born to consanguineous Pakistani parents, with MGCA3, Arif et al. (2013) identified a homozygous missense mutation in the OPA3 gene (L11Q; 606580.0005). The mutation, which was identified by genomewide homozygosity mapping and exome sequencing, segregated with the disorder in the family. The variant was not present in the NHLBI Exome Sequencing Project database. </p>
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<strong>REFERENCES</strong>
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Anikster, Y., Kleta, R., Shaag, A., Gahl, W. A., Elpeleg, O.
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<strong>Type III 3-methylglutaconic aciduria (optic atrophy plus syndrome, or Costeff optic atrophy syndrome): identification of the OPA3 gene and its founder mutation in Iraqi Jews.</strong>
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Am. J. Hum. Genet. 69: 1218-1224, 2001.
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[PubMed: 11668429]
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[Full Text: https://doi.org/10.1086/324651]
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Arif, B., Kumar, K. R., Seibler, P., Vulinovic, F., Fatima, A., Winkler, S., Nurnberg, G., Thiele, H., Nurnberg, P., Jamil, A. Z., Bruggemann, A., Abbas, G., Klein, C., Lohmann, K.
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Kleta, R., Skovby, F., Christensen, E., Rosenberg, T., Gahl, W. A., Anikster, Y.
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<strong>3-Methylglutaconic aciduria type III in a non-Iraqi-Jewish kindred: clinical and molecular findings.</strong>
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Nystuen, A., Costeff, H., Elpeleg, O. N., Apter, N., Bonne-Tamir, B., Mohrenweiser, H., Haider, N., Stone, E. M., Sheffield, V. C.
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<strong>Iraqi-Jewish kindreds with optic atrophy plus (3-methylglutaconic aciduria type 3) demonstrate linkage disequilibrium with the CTG repeat in the 3-prime untranslated region of the myotonic dystrophy protein kinase gene.</strong>
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<strong>Behr's syndrome and 3-methylglutaconic aciduria.</strong>
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Yahalom, G., Anikster, Y., Huna-Baron, R., Hoffmann, C., Blumkin, L., Lev, D., Tsabari, R., Nitsan, Z., Lerman, S. F., Ben-Zeev, B., Pode-Shakked, B., Sofer, S., Schweiger, A., Lerman-Sagie, T., Hassin-Baer, S.
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Hilary J. Vernon - updated : 06/16/2020<br>Cassandra L. Kniffin - updated : 10/12/2007<br>Marla J. F. O'Neill - updated : 6/19/2006<br>Victor A. McKusick - updated : 12/20/2001<br>Victor A. McKusick - updated : 4/24/1997
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Victor A. McKusick : 1/5/1990
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