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Entry
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- #607196 - MICROCEPHALY, AMISH TYPE; MCPHA
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- OMIM
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<p>
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<span class="h4">#607196</span>
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<br />
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<strong>Table of Contents</strong>
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</p>
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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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<li role="presentation">
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<a href="/clinicalSynopsis/607196"><strong>Clinical Synopsis</strong></a>
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<li role="presentation">
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<a href="/phenotypicSeries/PS249270"> <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="#inheritance">Inheritance</a>
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<a href="#biochemicalFeatures">Biochemical Features</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#clinicalManagement">Clinical Management</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div id="mimExternalLinksToggleTriangle" class="small" style="color: white; display: table-cell;">▼</div>
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<div style="display: table-cell;">External Links</div>
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</a>
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</h4>
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<div class="panel-heading mim-panel-heading" role="tab" id="mimClinicalResources">
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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</span>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://clinicaltrials.gov/search?cond=MICROCEPHALY, AMISH TYPE" 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=14315&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/NBK1365/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/376" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://medlineplus.gov/genetics/condition/amish-lethal-microcephaly" 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=607196[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=99742" 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/6fe19eb9-8c44-4c07-8140-e9c2307e1022/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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</div>
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</div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</span>
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</span>
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 702437000<br />
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<strong>ORPHA:</strong> 99742<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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607196
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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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MICROCEPHALY, AMISH TYPE; MCPHA
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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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AMISH LETHAL MICROCEPHALY<br />
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THIAMINE METABOLISM DYSFUNCTION SYNDROME 3 (MICROCEPHALY TYPE); THMD3
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="phenotypeMap" class="mim-anchor"></a>
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<h4>
|
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<span class="mim-font">
|
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<strong>Phenotype-Gene Relationships</strong>
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</span>
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</h4>
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<div>
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<table class="table table-bordered table-condensed 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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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td>
|
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<span class="mim-font">
|
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<a href="/geneMap/17/940?start=-3&limit=10&highlight=940">
|
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17q25.1
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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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Microcephaly, Amish type
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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/607196"> 607196 </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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SLC25A19
|
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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/606521"> 606521 </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 ">
|
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<a href="/clinicalSynopsis/607196" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
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<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
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<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 class="btn-group">
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<a href="/phenotypicSeries/PS249270" 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')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
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PheneGene Graphics <span class="caret"></span>
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</button>
|
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<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/607196" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/607196" 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>
|
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<span class="mim-font">
|
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|
|
- 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>
|
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<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
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<div>
|
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<div>
|
|
<span class="h5 mim-font">
|
|
<em> Head </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Microcephaly, extreme <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551919&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551919</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
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|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Face </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Micrognathia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/32958008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">32958008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M26.04" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M26.04</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/524.04" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">524.04</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0025990&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025990</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000347</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000347</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=9149eccae19753e96defbd69602ab882" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Micrognathia-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=9149eccae19753e96defbd69602ab882" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
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|
</span>
|
|
</div>
|
|
</div>
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|
|
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|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ABDOMEN </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Liver </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Hepatomegaly associated with infection <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551918&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551918</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> SKELETAL </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Contractures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/57048009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">57048009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/55033002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">55033002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/M62.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M62.40</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/M62.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">M62.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0009917&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009917</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Skull </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Nearly absent cranial vault <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551920&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551920</a>]</span><br /> -
|
|
Absence of anterior and posterior fontanelles <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551921&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551921</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEUROLOGIC </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Central Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- No psychomotor development <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/224958001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">224958001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F88</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0557874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0557874</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span><br /> -
|
|
Truncal hypotonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853743&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853743</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008936" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008936</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008936" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008936</a>]</span><br /> -
|
|
Limb hypertonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1838391&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1838391</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002509" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002509</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002509" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002509</a>]</span><br /> -
|
|
Immature brain with no gyral development <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551916&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551916</a>]</span><br /> -
|
|
Hypoplastic pons <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551917&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551917</a>]</span><br /> -
|
|
Partial agenesis of the corpus callosum <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253140003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253140003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0431368&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0431368</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001338" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001338</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001338" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001338</a>]</span><br /> -
|
|
Hypoplastic cerebellum <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16026008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16026008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0266470&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0266470</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001321" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001321</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001321" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001321</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Behavioral Psychiatric Manifestations </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Irritability <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/55929007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">55929007</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/799.22" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">799.22</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0022107&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022107</a>, <a href="https://bioportal.bioontology.org/search?q=C2700617&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2700617</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000737" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000737</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000737" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000737</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> METABOLIC FEATURES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Lactic acidosis during infection <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551928&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551928</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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|
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|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> LABORATORY ABNORMALITIES </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Increased urinary 2-ketoglutarate (variable) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3551922&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3551922</a>]</span><br /> -
|
|
Increased urinary lactate <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1839426&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1839426</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
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<span class="h5 mim-font">
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<strong> MISCELLANEOUS </strong>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Onset at birth <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1836142&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1836142</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003577" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003577</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003577" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003577</a>]</span><br /> -
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Progression of the disorder is precipitated by viral symptoms<br /> -
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Death usually within first year of life<br /> -
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Incidence of 1 in 480 among Old Order Amish<br /> -
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Carrier rate of 1 in 11 among Old Order Amish<br />
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</span>
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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 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 solute carrier family 25, member 19 gene (mitochondrial thiamine pyrophosphate carrier) (SLC25A19, <a href="/entry/606521#0001">606521.0001</a>)<br />
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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>
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Thiamine-responsive dysfunction syndrome
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- <a href="/phenotypicSeries/PS249270">PS249270</a>
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- 5 Entries
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</h5>
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</div>
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</div>
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<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
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<table class="table table-bordered table-condensed table-hover mim-table-padding">
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<thead>
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<tr>
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<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>
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<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>
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<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>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
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<strong>Phenotype<br />mapping key</strong>
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</th>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
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<strong>Phenotype<br />MIM number</strong>
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</th>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
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<strong>Gene/Locus</strong>
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</th>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
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<strong>Gene/Locus<br />MIM number</strong>
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/1/1403?start=-3&limit=10&highlight=1403"> 1q24.2 </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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<a href="/entry/249270"> Thiamine-responsive megaloblastic anemia syndrome </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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<a href="/entry/249270"> 249270 </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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<a href="/entry/603941"> SLC19A2 </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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<a href="/entry/603941"> 603941 </a>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/2/1075?start=-3&limit=10&highlight=1075"> 2q36.3 </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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<a href="/entry/607483"> Thiamine metabolism dysfunction syndrome 2 (biotin/thiamine-responsive basal ganglia disease type) </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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<a href="/entry/607483"> 607483 </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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<a href="/entry/606152"> SLC19A3 </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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<a href="/entry/606152"> 606152 </a>
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/7/784?start=-3&limit=10&highlight=784"> 7q35 </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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<a href="/entry/614458"> Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type) </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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|
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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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|
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</span>
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</td>
|
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<td>
|
|
<span class="mim-font">
|
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<a href="/entry/614458"> 614458 </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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<a href="/entry/606370"> TPK1 </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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<a href="/entry/606370"> 606370 </a>
|
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</span>
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</td>
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</tr>
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<tr>
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<td>
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<span class="mim-font">
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<a href="/geneMap/17/940?start=-3&limit=10&highlight=940"> 17q25.1 </a>
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
<a href="/entry/613710"> Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type) </a>
|
|
</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>
|
|
<span class="mim-font">
|
|
<a href="/entry/613710"> 613710 </a>
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606521"> SLC25A19 </a>
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606521"> 606521 </a>
|
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</span>
|
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</td>
|
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</tr>
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|
|
<tr>
|
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<td>
|
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<span class="mim-font">
|
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|
|
<a href="/geneMap/17/940?start=-3&limit=10&highlight=940"> 17q25.1 </a>
|
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|
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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/607196"> Microcephaly, Amish type </a>
|
|
</span>
|
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</td>
|
|
<td>
|
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<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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|
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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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|
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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/607196"> 607196 </a>
|
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
<a href="/entry/606521"> SLC25A19 </a>
|
|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
|
<a href="/entry/606521"> 606521 </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 class="text-right small">
|
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<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">▲ Close</a>
|
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</div>
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</div>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
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<strong>TEXT</strong>
|
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</span>
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</span>
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</h4>
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<div id="mimTextFold" class="collapse in ">
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because of evidence that Amish-type microcephaly, also known as thiamine metabolism dysfunction syndrome-3 (THMD3), is caused by homozygous mutation in the SLC25A19 gene (<a href="/entry/606521">606521</a>) on chromosome 17q25.</p><p>Thiamine metabolism dysfunction syndrome-4 (THMD4; <a href="/entry/613710">613710</a>) is an allelic disorder with a milder phenotype.</p>
|
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</span>
|
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<div>
|
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<br />
|
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</div>
|
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</div>
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<div>
|
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<a id="description" class="mim-anchor"></a>
|
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
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<span class="mim-font">
|
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<strong>Description</strong>
|
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</span>
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</h4>
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</div>
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<div id="mimDescriptionFold" class="collapse in ">
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<span class="mim-text-font">
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<p>Amish-type microcephaly (MCPHA) is a severe autosomal recessive metabolic disorder characterized by severe microcephaly apparent at birth, profoundly delayed psychomotor development, brain malformations, and episodic encephalopathy associated with lactic acidosis and alpha-ketoglutaric aciduria (summary by <a href="#1" class="mim-tip-reference" title="Kelley, R. I., Robinson, D., Puffenberger, E. G., Strauss, K. A., Morton, D. H. <strong>Amish lethal microcephaly: a new metabolic disorder with severe congenital microcephaly and 2-ketoglutaric aciduria.</strong> Am. J. Med. Genet. 112: 318-326, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12376931/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12376931</a>] [<a href="https://doi.org/10.1002/ajmg.10529" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12376931">Kelley et al., 2002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12376931" 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 disorders due to thiamine metabolism dysfunction, see THMD1 (<a href="/entry/249270">249270</a>).</p>
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</span>
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<div>
|
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<br />
|
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</div>
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</div>
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<div>
|
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<a id="clinicalFeatures" class="mim-anchor"></a>
|
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<h4 href="#mimClinicalFeaturesFold" id="mimClinicalFeaturesToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Clinical Features</strong>
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</span>
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</h4>
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</div>
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<div id="mimClinicalFeaturesFold" class="collapse in mimTextToggleFold">
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<span class="mim-text-font">
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<p><a href="#1" class="mim-tip-reference" title="Kelley, R. I., Robinson, D., Puffenberger, E. G., Strauss, K. A., Morton, D. H. <strong>Amish lethal microcephaly: a new metabolic disorder with severe congenital microcephaly and 2-ketoglutaric aciduria.</strong> Am. J. Med. Genet. 112: 318-326, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12376931/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12376931</a>] [<a href="https://doi.org/10.1002/ajmg.10529" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12376931">Kelley et al. (2002)</a> described a metabolic disorder among the Old Order Amish of Lancaster County, Pennsylvania, characterized by severe congenital microcephaly, death within the first year, and severe 2-ketoglutaric aciduria. The disorder segregated as an autosomal recessive and had the unusually high incidence of at least 1 in 500 births. When the infants were well, urine organic acid profiles showed isolated, extreme elevations of 2-ketoglutaric acid. However, during otherwise simple viral illnesses, the infants often developed metabolic acidosis, which sometimes followed a lethal course. Cranial MRI of 1 patient showed a smooth, immature brain similar to that of a 20-week fetus except for a moderate degree of cerebellar vermal hypoplasia. Assay of 2-ketoglutarate dehydrogenase (<a href="/entry/613022">613022</a>) in cultured lymphoblasts of 1 patient showed normal activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12376931" 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="#2" class="mim-tip-reference" title="Rosenberg, M. J., Agarwala, R., Bouffard, G., Davis, J., Fiermonte, G., Hilliard, M. S., Koch, T., Kalikin, L. M., Makalowska, I., Morton, D. H., Petty, E. M., Weber, J. L., Palmieri, F., Kelley, R. I., Schaffer, A. A., Biesecker, L. G. <strong>Mutant deoxynucleotide carrier is associated with congenital microcephaly.</strong> Nature Genet. 32: 175-179, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12185364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12185364</a>] [<a href="https://doi.org/10.1038/ng948" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12185364">Rosenberg et al. (2002)</a> stated that at least 61 affected infants had been born in the previous 40 years in 23 nuclear families. Affected individuals had head circumferences that were 6 to 12 SD less than the population mean. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12185364" 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="Siu, V. M., Ratko, S., Prasad, A. N., Prasad, C., Rupar, C. A. <strong>Amish microcephaly: Long-term survival and biochemical characterization.</strong> Am. J. Med. Genet. 152A: 1747-1751, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20583149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20583149</a>] [<a href="https://doi.org/10.1002/ajmg.a.33373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20583149">Siu et al. (2010)</a> reported a male infant with Amish microcephaly. He was born of distantly related parents in Ontario, Canada, who had Amish ancestors. Microcephaly was first noted at 21 weeks' gestation. At birth, he showed severe microcephaly, a sloping forehead, and extremely small anterior fontanel. He had truncal hypotonia with hypertonia of the extremities, spontaneous myoclonic jerks, and optic nerve atrophy with foveal hypoplasia. He exhibited extreme irritability and developed failure to thrive. Brain MRI showed partial agenesis of the corpus callosum, large cisterna magna communicating with the fourth ventricle, enlarged lateral ventricles, hypoplastic cerebellar vermis, and lissencephaly. He also had spinal dysraphism and osteopenia. The patient was alive at 7 years, with a static microcephaly, profound developmental delay, and metabolic lactic acidosis controlled by a high fat diet. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20583149" 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 MCPHA in the family reported by <a href="#3" class="mim-tip-reference" title="Siu, V. M., Ratko, S., Prasad, A. N., Prasad, C., Rupar, C. A. <strong>Amish microcephaly: Long-term survival and biochemical characterization.</strong> Am. J. Med. Genet. 152A: 1747-1751, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20583149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20583149</a>] [<a href="https://doi.org/10.1002/ajmg.a.33373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20583149">Siu et al. (2010)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20583149" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In the patient with MCPHA reported by <a href="#3" class="mim-tip-reference" title="Siu, V. M., Ratko, S., Prasad, A. N., Prasad, C., Rupar, C. A. <strong>Amish microcephaly: Long-term survival and biochemical characterization.</strong> Am. J. Med. Genet. 152A: 1747-1751, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20583149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20583149</a>] [<a href="https://doi.org/10.1002/ajmg.a.33373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20583149">Siu et al. (2010)</a>, lactic acidosis was present from birth, but urinary alpha-ketoglutarate did not appear until age 8 months, even during metabolic crisis. After institution of a high-fat diet, lactate decreased and urinary alpha-ketoglutarate increased. These findings indicated that increased urine alpha-ketoglutaric acid is not a constant feature of MCPHA. <a href="#3" class="mim-tip-reference" title="Siu, V. M., Ratko, S., Prasad, A. N., Prasad, C., Rupar, C. A. <strong>Amish microcephaly: Long-term survival and biochemical characterization.</strong> Am. J. Med. Genet. 152A: 1747-1751, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20583149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20583149</a>] [<a href="https://doi.org/10.1002/ajmg.a.33373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20583149">Siu et al. (2010)</a> noted that, since mutations in the SLC25A19 gene result in a thiamine deficiency, these biochemical characteristics could be explained by deficient activities of 2 of the 3 mitochondrial thiamine-requiring enzymes, pyruvate dehydrogenase (PDC) and alpha-ketoglutaric acid dehydrogenase. During metabolic crisis, there is reduced PDC activity, resulting in lactic acidosis and less acetyl-CoA entering the citric acid cycle, with decreased production of alpha-ketoglutarate. Later accumulation of alpha-ketoglutarate may occur because thiamine deficiency reduces alpha-ketoglutaric acid dehydrogenase activity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20583149" 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="#3" class="mim-tip-reference" title="Siu, V. M., Ratko, S., Prasad, A. N., Prasad, C., Rupar, C. A. <strong>Amish microcephaly: Long-term survival and biochemical characterization.</strong> Am. J. Med. Genet. 152A: 1747-1751, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20583149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20583149</a>] [<a href="https://doi.org/10.1002/ajmg.a.33373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20583149">Siu et al. (2010)</a> reported that their patient with MCPHA was treated successfully with a high-fat diet, which likely provided energy in mitochondria primarily through fatty acid beta-oxidation, bypassing pyruvate dehydrogenase to directly enter the tricarboxylic acid cycle. Importantly, the metabolic similarity of MCPHA to pyruvate dehydrogenase deficiency (see, e.g., <a href="/entry/312070">312070</a>) indicates that glucose should be administered with caution to patients with MCPHA to avoid a risk of exacerbating the lactic acidemia. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20583149" 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>Through a whole-genome scan, fine mapping, and haplotype analysis, <a href="#2" class="mim-tip-reference" title="Rosenberg, M. J., Agarwala, R., Bouffard, G., Davis, J., Fiermonte, G., Hilliard, M. S., Koch, T., Kalikin, L. M., Makalowska, I., Morton, D. H., Petty, E. M., Weber, J. L., Palmieri, F., Kelley, R. I., Schaffer, A. A., Biesecker, L. G. <strong>Mutant deoxynucleotide carrier is associated with congenital microcephaly.</strong> Nature Genet. 32: 175-179, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12185364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12185364</a>] [<a href="https://doi.org/10.1038/ng948" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12185364">Rosenberg et al. (2002)</a> mapped a locus for Amish microcephaly to a region of 2 Mb on chromosome 17q25. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12185364" 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="#2" class="mim-tip-reference" title="Rosenberg, M. J., Agarwala, R., Bouffard, G., Davis, J., Fiermonte, G., Hilliard, M. S., Koch, T., Kalikin, L. M., Makalowska, I., Morton, D. H., Petty, E. M., Weber, J. L., Palmieri, F., Kelley, R. I., Schaffer, A. A., Biesecker, L. G. <strong>Mutant deoxynucleotide carrier is associated with congenital microcephaly.</strong> Nature Genet. 32: 175-179, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12185364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12185364</a>] [<a href="https://doi.org/10.1038/ng948" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12185364">Rosenberg et al. (2002)</a> identified a list of positional candidate genes, comprising 7 full-length cDNAs, 3 EST clusters, and 11 predicted genes. The authors reasoned that because alpha-ketoglutarate is a component of the Krebs cycle, the alpha-ketoglutarate abnormality in MCPHA could be an indication of mitochondrial dysfunction. Two of the genes on the list of candidates, SLC25A19 and ATP5H (ATP5PD; <a href="/entry/618121">618121</a>), encode proteins with known mitochondrial functions and therefore were particularly attractive candidates. The coding region of the ATP5H gene was normal, but <a href="#2" class="mim-tip-reference" title="Rosenberg, M. J., Agarwala, R., Bouffard, G., Davis, J., Fiermonte, G., Hilliard, M. S., Koch, T., Kalikin, L. M., Makalowska, I., Morton, D. H., Petty, E. M., Weber, J. L., Palmieri, F., Kelley, R. I., Schaffer, A. A., Biesecker, L. G. <strong>Mutant deoxynucleotide carrier is associated with congenital microcephaly.</strong> Nature Genet. 32: 175-179, 2002.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12185364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12185364</a>] [<a href="https://doi.org/10.1038/ng948" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12185364">Rosenberg et al. (2002)</a> identified a homozygous nucleotide change in the coding region of SLC25A19 gene in an affected child (G177A; <a href="/entry/606521#0001">606521.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12185364" 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 male child with Amish microcephaly, <a href="#3" class="mim-tip-reference" title="Siu, V. M., Ratko, S., Prasad, A. N., Prasad, C., Rupar, C. A. <strong>Amish microcephaly: Long-term survival and biochemical characterization.</strong> Am. J. Med. Genet. 152A: 1747-1751, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20583149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20583149</a>] [<a href="https://doi.org/10.1002/ajmg.a.33373" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20583149">Siu et al. (2010)</a> found the same homozygous G177A mutation (<a href="/entry/606521#0001">606521.0001</a>) observed in other Amish patients with the disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20583149" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>Amish lethal microcephaly: a new metabolic disorder with severe congenital microcephaly and 2-ketoglutaric aciduria.</strong>
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Am. J. Med. Genet. 112: 318-326, 2002.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12376931/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12376931</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12376931" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Rosenberg, M. J., Agarwala, R., Bouffard, G., Davis, J., Fiermonte, G., Hilliard, M. S., Koch, T., Kalikin, L. M., Makalowska, I., Morton, D. H., Petty, E. M., Weber, J. L., Palmieri, F., Kelley, R. I., Schaffer, A. A., Biesecker, L. G.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12185364/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12185364</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12185364" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<strong>Amish microcephaly: Long-term survival and biochemical characterization.</strong>
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Am. J. Med. Genet. 152A: 1747-1751, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20583149/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20583149</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20583149" 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="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 10/28/2010
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<span class="mim-text-font">
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Victor A. McKusick - updated : 9/3/2002
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Creation Date:
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<span class="mim-text-font">
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Victor A. McKusick : 9/3/2002
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<span class="mim-text-font">
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alopez : 02/06/2024
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carol : 08/03/2020<br>mgross : 09/13/2018<br>carol : 02/10/2012<br>ckniffin : 2/8/2012<br>wwang : 11/10/2010<br>ckniffin : 10/28/2010<br>carol : 9/22/2009<br>carol : 9/18/2009<br>alopez : 6/13/2005<br>alopez : 10/18/2002<br>carol : 9/18/2002<br>tkritzer : 9/6/2002<br>tkritzer : 9/3/2002
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<span class="mim-font">
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<strong>#</strong> 607196
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MICROCEPHALY, AMISH TYPE; MCPHA
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<em>Alternative titles; symbols</em>
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AMISH LETHAL MICROCEPHALY<br />
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THIAMINE METABOLISM DYSFUNCTION SYNDROME 3 (MICROCEPHALY TYPE); THMD3
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<strong>SNOMEDCT:</strong> 702437000;
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<strong>ORPHA:</strong> 99742;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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<span class="mim-font">
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17q25.1
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<span class="mim-font">
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Microcephaly, Amish type
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607196
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Autosomal recessive
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<span class="mim-font">
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3
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SLC25A19
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606521
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that Amish-type microcephaly, also known as thiamine metabolism dysfunction syndrome-3 (THMD3), is caused by homozygous mutation in the SLC25A19 gene (606521) on chromosome 17q25.</p><p>Thiamine metabolism dysfunction syndrome-4 (THMD4; 613710) is an allelic disorder with a milder phenotype.</p>
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<strong>Description</strong>
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<p>Amish-type microcephaly (MCPHA) is a severe autosomal recessive metabolic disorder characterized by severe microcephaly apparent at birth, profoundly delayed psychomotor development, brain malformations, and episodic encephalopathy associated with lactic acidosis and alpha-ketoglutaric aciduria (summary by Kelley et al., 2002). </p><p>For a discussion of genetic heterogeneity of disorders due to thiamine metabolism dysfunction, see THMD1 (249270).</p>
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<strong>Clinical Features</strong>
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<p>Kelley et al. (2002) described a metabolic disorder among the Old Order Amish of Lancaster County, Pennsylvania, characterized by severe congenital microcephaly, death within the first year, and severe 2-ketoglutaric aciduria. The disorder segregated as an autosomal recessive and had the unusually high incidence of at least 1 in 500 births. When the infants were well, urine organic acid profiles showed isolated, extreme elevations of 2-ketoglutaric acid. However, during otherwise simple viral illnesses, the infants often developed metabolic acidosis, which sometimes followed a lethal course. Cranial MRI of 1 patient showed a smooth, immature brain similar to that of a 20-week fetus except for a moderate degree of cerebellar vermal hypoplasia. Assay of 2-ketoglutarate dehydrogenase (613022) in cultured lymphoblasts of 1 patient showed normal activity. </p><p>Rosenberg et al. (2002) stated that at least 61 affected infants had been born in the previous 40 years in 23 nuclear families. Affected individuals had head circumferences that were 6 to 12 SD less than the population mean. </p><p>Siu et al. (2010) reported a male infant with Amish microcephaly. He was born of distantly related parents in Ontario, Canada, who had Amish ancestors. Microcephaly was first noted at 21 weeks' gestation. At birth, he showed severe microcephaly, a sloping forehead, and extremely small anterior fontanel. He had truncal hypotonia with hypertonia of the extremities, spontaneous myoclonic jerks, and optic nerve atrophy with foveal hypoplasia. He exhibited extreme irritability and developed failure to thrive. Brain MRI showed partial agenesis of the corpus callosum, large cisterna magna communicating with the fourth ventricle, enlarged lateral ventricles, hypoplastic cerebellar vermis, and lissencephaly. He also had spinal dysraphism and osteopenia. The patient was alive at 7 years, with a static microcephaly, profound developmental delay, and metabolic lactic acidosis controlled by a high fat diet. </p>
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<span class="mim-font">
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<strong>Inheritance</strong>
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</h4>
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<p>The transmission pattern of MCPHA in the family reported by Siu et al. (2010) was consistent with autosomal recessive inheritance. </p>
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<strong>Biochemical Features</strong>
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<p>In the patient with MCPHA reported by Siu et al. (2010), lactic acidosis was present from birth, but urinary alpha-ketoglutarate did not appear until age 8 months, even during metabolic crisis. After institution of a high-fat diet, lactate decreased and urinary alpha-ketoglutarate increased. These findings indicated that increased urine alpha-ketoglutaric acid is not a constant feature of MCPHA. Siu et al. (2010) noted that, since mutations in the SLC25A19 gene result in a thiamine deficiency, these biochemical characteristics could be explained by deficient activities of 2 of the 3 mitochondrial thiamine-requiring enzymes, pyruvate dehydrogenase (PDC) and alpha-ketoglutaric acid dehydrogenase. During metabolic crisis, there is reduced PDC activity, resulting in lactic acidosis and less acetyl-CoA entering the citric acid cycle, with decreased production of alpha-ketoglutarate. Later accumulation of alpha-ketoglutarate may occur because thiamine deficiency reduces alpha-ketoglutaric acid dehydrogenase activity. </p>
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<strong>Clinical Management</strong>
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<p>Siu et al. (2010) reported that their patient with MCPHA was treated successfully with a high-fat diet, which likely provided energy in mitochondria primarily through fatty acid beta-oxidation, bypassing pyruvate dehydrogenase to directly enter the tricarboxylic acid cycle. Importantly, the metabolic similarity of MCPHA to pyruvate dehydrogenase deficiency (see, e.g., 312070) indicates that glucose should be administered with caution to patients with MCPHA to avoid a risk of exacerbating the lactic acidemia. </p>
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<span class="mim-font">
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<strong>Mapping</strong>
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<span class="mim-text-font">
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<p>Through a whole-genome scan, fine mapping, and haplotype analysis, Rosenberg et al. (2002) mapped a locus for Amish microcephaly to a region of 2 Mb on chromosome 17q25. </p>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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<span class="mim-text-font">
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<p>Rosenberg et al. (2002) identified a list of positional candidate genes, comprising 7 full-length cDNAs, 3 EST clusters, and 11 predicted genes. The authors reasoned that because alpha-ketoglutarate is a component of the Krebs cycle, the alpha-ketoglutarate abnormality in MCPHA could be an indication of mitochondrial dysfunction. Two of the genes on the list of candidates, SLC25A19 and ATP5H (ATP5PD; 618121), encode proteins with known mitochondrial functions and therefore were particularly attractive candidates. The coding region of the ATP5H gene was normal, but Rosenberg et al. (2002) identified a homozygous nucleotide change in the coding region of SLC25A19 gene in an affected child (G177A; 606521.0001). </p><p>In a male child with Amish microcephaly, Siu et al. (2010) found the same homozygous G177A mutation (606521.0001) observed in other Amish patients with the disorder. </p>
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<strong>REFERENCES</strong>
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<p />
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<p class="mim-text-font">
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Kelley, R. I., Robinson, D., Puffenberger, E. G., Strauss, K. A., Morton, D. H.
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<strong>Amish lethal microcephaly: a new metabolic disorder with severe congenital microcephaly and 2-ketoglutaric aciduria.</strong>
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Am. J. Med. Genet. 112: 318-326, 2002.
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[PubMed: 12376931]
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[Full Text: https://doi.org/10.1002/ajmg.10529]
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Rosenberg, M. J., Agarwala, R., Bouffard, G., Davis, J., Fiermonte, G., Hilliard, M. S., Koch, T., Kalikin, L. M., Makalowska, I., Morton, D. H., Petty, E. M., Weber, J. L., Palmieri, F., Kelley, R. I., Schaffer, A. A., Biesecker, L. G.
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<strong>Mutant deoxynucleotide carrier is associated with congenital microcephaly.</strong>
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Nature Genet. 32: 175-179, 2002.
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[PubMed: 12185364]
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[Full Text: https://doi.org/10.1038/ng948]
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<li>
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<p class="mim-text-font">
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Siu, V. M., Ratko, S., Prasad, A. N., Prasad, C., Rupar, C. A.
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<strong>Amish microcephaly: Long-term survival and biochemical characterization.</strong>
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Am. J. Med. Genet. 152A: 1747-1751, 2010.
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[PubMed: 20583149]
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[Full Text: https://doi.org/10.1002/ajmg.a.33373]
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<span class="text-nowrap mim-text-font">
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Contributors:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 10/28/2010<br>Victor A. McKusick - updated : 9/3/2002
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<span class="text-nowrap mim-text-font">
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Creation Date:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 9/3/2002
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<span class="text-nowrap mim-text-font">
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Edit History:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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alopez : 02/06/2024<br>carol : 08/03/2020<br>mgross : 09/13/2018<br>carol : 02/10/2012<br>ckniffin : 2/8/2012<br>wwang : 11/10/2010<br>ckniffin : 10/28/2010<br>carol : 9/22/2009<br>carol : 9/18/2009<br>alopez : 6/13/2005<br>alopez : 10/18/2002<br>carol : 9/18/2002<br>tkritzer : 9/6/2002<br>tkritzer : 9/3/2002
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