2786 lines
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- #613710 - THIAMINE METABOLISM DYSFUNCTION SYNDROME 4 (BILATERAL STRIATAL DEGENERATION AND PROGRESSIVE POLYNEUROPATHY TYPE); THMD4
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<p>
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<span class="h4">#613710</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/613710"><strong>Clinical Synopsis</strong></a>
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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="#clinicalManagement">Clinical Management</a>
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<li role="presentation" style="margin-left: 1em">
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div style="display: table-cell;">External Links</div>
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</a>
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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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<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=THIAMINE METABOLISM DYSFUNCTION SYNDROME 4 (BILATERAL STRIATAL DEGENERATION AND PROGRESSIVE POLYNEUROPATHY 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=18854&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/9361" 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://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=613710[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=217396" 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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<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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<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> 771305006<br />
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<strong>ORPHA:</strong> 217396<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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613710
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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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THIAMINE METABOLISM DYSFUNCTION SYNDROME 4 (BILATERAL STRIATAL DEGENERATION AND PROGRESSIVE POLYNEUROPATHY TYPE); THMD4
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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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BILATERAL STRIATAL DEGENERATION AND PROGRESSIVE POLYNEUROPATHY<br />
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STRIATAL NECROSIS, BILATERAL, AND PROGRESSIVE POLYNEUROPATHY
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="phenotypeMap" class="mim-anchor"></a>
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<h4>
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<span class="mim-font">
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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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<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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Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type)
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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/613710"> 613710 </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 class="btn-group ">
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<a href="/clinicalSynopsis/613710" 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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<div class="btn-group">
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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;">
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<li><a href="/graph/linear/613710" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/613710" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
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</ul>
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</div>
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<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<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">
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<strong> INHERITANCE </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- 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">
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<strong> SKELETAL </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Distal joint contractures, lower limbs <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3279111&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3279111</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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<span class="h5 mim-font">
|
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<em> Hands </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Trigger finger deformity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3280311&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3280311</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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<span class="h5 mim-font">
|
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<em> Feet </em>
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</span>
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</div>
|
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<div style="margin-left: 2em;">
|
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<span class="mim-font">
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- Foot deformities <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/229844004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">229844004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0016506&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0016506</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001760" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001760</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001760" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001760</a>]</span><br /> -
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Forefoot adduction <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3279112&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3279112</a>]</span><br /> -
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Forefoot supination <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3279113&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3279113</a>]</span><br /> -
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Pes equinus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/37718006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">37718006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/397932003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">397932003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1156475005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1156475005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q66.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q66.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q66.89" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q66.89</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/754.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">754.51</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/736.72" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">736.72</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0158490&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0158490</a>, <a href="https://bioportal.bioontology.org/search?q=C0009081&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009081</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001762" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001762</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001762" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001762</a>]</span><br /> -
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|
Pes equinovalgus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/68284008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">68284008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0265642&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0265642</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001772" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001772</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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<div>
|
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<span class="h5 mim-font">
|
|
<strong> MUSCLE, SOFT TISSUES </strong>
|
|
</span>
|
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</div>
|
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<div style="margin-left: 2em;">
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<div>
|
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<span class="mim-font">
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|
|
- Distal muscle weakness due to neuropathy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3279109&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3279109</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249942005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249942005</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002460" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002460</a>]</span><br /> -
|
|
Distal muscle atrophy due to neuropathy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3279110&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3279110</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003693" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003693</a>]</span><br />
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|
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</span>
|
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</div>
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</div>
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</div>
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<div>
|
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<div>
|
|
<span class="h5 mim-font">
|
|
<strong> NEUROLOGIC </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
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<div>
|
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<div>
|
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<span class="h5 mim-font">
|
|
<em> Central Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Encephalopathic attacks, episodic, associated with infection <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3279105&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3279105</a>]</span><br /> -
|
|
Lethargy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/214264003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">214264003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R53.83" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R53.83</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0023380&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0023380</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001254" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001254</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001254" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001254</a>]</span><br /> -
|
|
Weakness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/13791008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">13791008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R53.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R53.81</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R53.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R53.1</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/799.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">799.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714552&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714552</a>, <a href="https://bioportal.bioontology.org/search?q=C0004093&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0004093</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0025406" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0025406</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0025406" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0025406</a>]</span><br /> -
|
|
Paralysis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/44695005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">44695005</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/344.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">344.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0522224&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0522224</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003470" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003470</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003470" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003470</a>]</span><br /> -
|
|
Truncal ataxia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/250067008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">250067008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0427190&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0427190</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002078" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002078</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002078" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002078</a>]</span><br /> -
|
|
Difficulty walking and running <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1866014&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1866014</a>]</span><br /> -
|
|
Toe walking <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/250018006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">250018006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0427144&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0427144</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030051" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030051</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0030051" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0030051</a>]</span><br /> -
|
|
Abnormal gait <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/22325002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">22325002</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/781.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">781.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0575081&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0575081</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001288" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001288</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001288" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001288</a>]</span><br /> -
|
|
Dysphonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16617009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16617009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R49.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R49.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/784.42" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">784.42</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1527344&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1527344</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001618" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001618</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001618" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001618</a>]</span><br /> -
|
|
Dysarthria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8011004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8011004</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.13" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.13</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/784.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">784.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span><br /> -
|
|
Lesions in the caudate and putamen seen on MRI <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3279106&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3279106</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Peripheral Nervous System </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Axonal neuropathy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/60703000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">60703000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0270921&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0270921</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003477" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003477</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003477" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003477</a>]</span><br /> -
|
|
Distal muscle weakness due to neuropathy (lower limbs more affected than upper limbs) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3279107&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3279107</a>]</span> <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/249942005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">249942005</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002460" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002460</a>]</span><br /> -
|
|
Distal muscle atrophy due to neuropathy (lower limbs more affected than upper limbs) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3279108&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3279108</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003693" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003693</a>]</span><br /> -
|
|
Hyporeflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/835279003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">835279003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405946002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405946002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0700078&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700078</a>, <a href="https://bioportal.bioontology.org/search?q=C0151888&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151888</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001265" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001265</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001315" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001315</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001265" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001265</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
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|
|
|
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|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> VOICE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Dysphonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16617009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16617009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R49.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R49.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/784.42" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">784.42</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1527344&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1527344</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001618" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001618</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001618" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001618</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
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|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
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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 CSF lactate during acute episodes <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3279114&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3279114</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MISCELLANEOUS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Onset of acute encephalopathic attacks in childhood (3 to 7 years)<br /> -
|
|
Onset usually associated with febrile illness<br /> -
|
|
Full recovery after attacks<br /> -
|
|
Onset of chronic progressive polyneuropathy in late childhood<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> MOLECULAR BASIS </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Caused by mutation in the solute carrier family 25 (mitochondrial thiamine pyrophosphate carrier), member 19 gene (SLC25A19, <a href="/entry/606521#0002">606521.0002</a>)<br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="text-right">
|
|
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="row">
|
|
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
|
|
<h5>
|
|
Thiamine-responsive dysfunction syndrome
|
|
- <a href="/phenotypicSeries/PS249270">PS249270</a>
|
|
- 5 Entries
|
|
</h5>
|
|
</div>
|
|
</div>
|
|
|
|
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
|
<table class="table table-bordered table-condensed table-hover mim-table-padding">
|
|
<thead>
|
|
<tr>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Location</strong>
|
|
</th>
|
|
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
|
|
<strong>Phenotype</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Inheritance</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />mapping key</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Phenotype<br />MIM number</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus</strong>
|
|
</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
|
</th>
|
|
</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/1/1403?start=-3&limit=10&highlight=1403"> 1q24.2 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/249270"> Thiamine-responsive megaloblastic anemia syndrome </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/249270"> 249270 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603941"> SLC19A2 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/603941"> 603941 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/2/1075?start=-3&limit=10&highlight=1075"> 2q36.3 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607483"> Thiamine metabolism dysfunction syndrome 2 (biotin/thiamine-responsive basal ganglia disease type) </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607483"> 607483 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606152"> SLC19A3 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606152"> 606152 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/7/784?start=-3&limit=10&highlight=784"> 7q35 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614458"> Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type) </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/614458"> 614458 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606370"> TPK1 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606370"> 606370 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<a href="/geneMap/17/940?start=-3&limit=10&highlight=940"> 17q25.1 </a>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607196"> Microcephaly, Amish type </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
|
|
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
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<p>A number sign (#) is used with this entry because thiamine metabolism dysfunction syndrome-4 (THMD4), also known as bilateral striatal degeneration and progressive polyneuropathy, is caused by homozygous or compound heterozygous mutation in the SLC25A19 gene (<a href="/entry/606521">606521</a>) on chromosome 17q25.</p><p>Amish lethal microcephaly (MCPHA; <a href="/entry/607196">607196</a>) is an allelic disorder with a more severe phenotype.</p>
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<p>Thiamine metabolism dysfunction syndrome-4 (THMD4) is an autosomal recessive metabolic disorder characterized by childhood onset of episodic encephalopathy, often associated with a febrile illness, and causing transient neurologic dysfunction. Most patients recover fully, but some may have mild residual weakness. Affected individuals also develop a slowly progressive axonal polyneuropathy beginning in childhood. Brain imaging during the acute episodes shows lesions consistent with bilateral striatal degeneration or necrosis (summary by <a href="#7" class="mim-tip-reference" title="Spiegel, R., Shaag, A., Edvardson, S., Mandel, H., Stepensky, P., Shalev, S. A., Horovitz, Y., Pines, O., Elpeleg, O. <strong>SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis.</strong> Ann. Neurol. 66: 419-424, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19798730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19798730</a>] [<a href="https://doi.org/10.1002/ana.21752" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19798730">Spiegel et al., 2009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19798730" 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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<p><a href="#7" class="mim-tip-reference" title="Spiegel, R., Shaag, A., Edvardson, S., Mandel, H., Stepensky, P., Shalev, S. A., Horovitz, Y., Pines, O., Elpeleg, O. <strong>SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis.</strong> Ann. Neurol. 66: 419-424, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19798730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19798730</a>] [<a href="https://doi.org/10.1002/ana.21752" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19798730">Spiegel et al. (2009)</a> reported a consanguineous Arab Muslim family in which 4 sibs had a disorder characterized by acute encephalopathic episodes associated with striatal necrosis on brain imaging as well as a progressive chronic polyneuropathy. All patients had normal early psychomotor development, with onset of episodic acute encephalopathic episodes in childhood between ages 3.5 and 6.5 years. These episodes were associated with nonspecific febrile illness and were characterized by lethargy, muscle weakness resulting in paralysis, areflexia, and dysarthria. These episodes were followed by complete resolution and no loss of psychomotor development, although most had residual mild distal weakness. Laboratory investigations showed mild increased lactate in the cerebrospinal fluid (CSF) during the acute phase, and brain imaging showed bilateral multiple T2-hyperintense lesions in the caudate and putamen, with sparing of the globus pallidus. In addition to encephalopathic episodes, all sibs had childhood onset of progressive chronic polyneuropathy characterized by motor difficulties, frequent falls, and distal weakness and atrophy of the lower limbs, accompanied by lower limb contractures and foot deformities. Electrophysiologic studies showed an axonal motor neuropathy. All sibs had age-appropriate cognition at ages 7 to 20 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19798730" 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="#1" class="mim-tip-reference" title="Bottega, R., Perrone, M. D., Vecchiato, K., Taddio, A., Sabui, S., Pecile, V., Said, H. M., Faletra, F. <strong>Functional analysis of the third identified SLC25A19 mutation causative for the thiamine metabolism dysfunction syndrome 4.</strong> J. Hum. Genet. 64: 1075-1081, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31506564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31506564</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31506564[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/s10038-019-0666-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31506564">Bottega et al. (2019)</a> reported a patient who had a history of neurologic impairment due to acute encephalopathic events in the setting of fevers at 1 year of age. The events were characterized by tremor, hypotonia, gait difficulties, dysphagia, dysphonia, and altered consciousness. At 18 years of age, he had moderate cognitive delay, pes cavus, and atrophy of the interosseous muscles. Electromyography showed a motor and sensory neuropathy. Brain MRI showed abnormal signal in the caudate nucleus, putamen, and insula cortex. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31506564" 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="Gowda, V. K., Srinivasan, V. M., Jehta, K., Bhat, M. D. <strong>Bilateral striatal necrosis with polyneuropathy with a novel SLC25A19 (mitochondrial thiamine pyrophosphate carrier OMIM*606521) mutation: treatable thiamine metabolic disorder--a report of two Indian cases.</strong> Neuropediatrics 50: 313-317, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31295743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31295743</a>] [<a href="https://doi.org/10.1055/s-0039-1693148" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31295743">Gowda et al. (2019)</a> reported clinical features in a 36-month-old boy and a 5-year-old girl. The boy presented with acute weakness and encephalopathy in the setting of gastroenteritis at 11 months of age. He recovered after 3 months, but at 23 months of age and 33 months of age he had recurrent episodes of acute encephalopathy. After initiation of oral thiamine, he regained lost developmental milestones. Brain MRI showed hyperintensity of the bilateral basal ganglia and thalami. Nerve conduction studies showed axonal neuropathy. Laboratory tests demonstrated elevated serum lactate. The girl presented at 16 months of age with encephalopathy in the setting of a febrile illness. She had incomplete recovery but had another episode of encephalopathy with febrile illness at 2 years and 6 months of age. Brain MRI at 16 months of age showed hyperintensity in the basal ganglia and thalami. Nerve conduction testing showed an axonal neuropathy, which improved after thiamine supplementation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31295743" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Li, D., Song, J., Li, X., Liu, Y., Dong, H., Kang, L., Liu, Y., Zhang, Y., Jin, Y., Guan, H., Zhou, C., Yang, Y. <strong>Eleven novel mutations and clinical characteristics in seven Chinese patients with thiamine metabolism dysfunction syndrome.</strong> Europ. J. Med. Genet. 63: 104003, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32679198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32679198</a>] [<a href="https://doi.org/10.1016/j.ejmg.2020.104003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32679198">Li et al. (2020)</a> described 2 patients with recurrent encephalopathic episodes, abnormal signal in the putamen and caudate nucleus on brain MRI, and elevated alpha-ketoglutarate in the urine. Patient 5, aged 2 years and 10 months, and patient 6, aged 2 years and 3 months, had normal intelligence and slight motor developmental delay. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32679198" 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="Chen, Y., Fang, B., Hu, X., Guo, R., Guo, J., Fang, K., Ni, J., Li, W., Qian, S., Hao, C. <strong>Identification and functional analysis of novel SLC25A19 variants causing thiamine metabolism dysfunction syndrome 4.</strong> Orphanet J. Rare Dis. 16: 403, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34587972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34587972</a>] [<a href="https://doi.org/10.1186/s13023-021-02028-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34587972">Chen et al. (2021)</a> reported 2 sibs (patients 2 and 3) who presented with coma in the setting of influenza A infection. Brain MRI in both sibs showed abnormal signal in the basal ganglia. Both patients required mechanical ventilation but recovered spontaneous respiration. Three months after discharge and despite being started on oral thiamine, both sibs had high muscle tone, absence of speech, and occasional gaze towards sound. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34587972" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Samur, B. M., Gumus, G., Canpolat, M., Gumus, H., Per, H., Caglayan, A. O. <strong>Clinical and genetic studies of thiamine metabolism dysfunction syndrome-4: case series and review of the literature.</strong> Clin. Dysmorph. 31: 125-131, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35102031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35102031</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35102031[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1097/MCD.0000000000000411" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35102031">Samur et al. (2022)</a> reported 3 patients with episodic encephalopathy, abnormal gait, and polyneuropathy. Patients 1 and 2 were 11- and 13-year-old brothers, respectively. Patient 1 began having encephalopathic episodes at 2 years of age. The episodes subsequently occurred every 2 to 3 years and were triggered by respiratory tract infections. He also had dysarthria, muscle weakness, ataxia and pes equinovarus. Brain MRI showed white matter hyperintensities and necrotic degeneration of the caudate, putamen, and thalamus. Patient 2 additionally had dysphonia, seizures, muscle weakness, and areflexia. His brain MRI showed degenerative changes in the bilateral caudate nuclei. Patient 3 was a 16-year-old girl who began having encephalopathic episodes at 4 years of age. She also had ataxia, increased muscle tone, and pes equinovarus. Brain MRI showed bilateral striatal necrosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35102031" 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 THMD4 in the consanguineous family reported by <a href="#7" class="mim-tip-reference" title="Spiegel, R., Shaag, A., Edvardson, S., Mandel, H., Stepensky, P., Shalev, S. A., Horovitz, Y., Pines, O., Elpeleg, O. <strong>SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis.</strong> Ann. Neurol. 66: 419-424, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19798730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19798730</a>] [<a href="https://doi.org/10.1002/ana.21752" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19798730">Spiegel et al. (2009)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19798730" 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="#5" class="mim-tip-reference" title="Porta, F., Siri, B., Chiesa, N., Ricci, F., Nika, L., Sciortino, P., Spada, M. <strong>SLC25A19 deficiency and bilateral striatal necrosis with polyneuropathy: a new case and review of the literature.</strong> J. Pediat. Endocr. Metab. 34: 261-266, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33544541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33544541</a>] [<a href="https://doi.org/10.1515/jpem-2020-0139" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33544541">Porta et al. (2021)</a> described response to thiamine treatment in 9 patients with THMD4, 8 of whom had previously been reported. Metabolic decompensations were recurrent and triggered by febrile episodes in the patients prior to thiamine treatment. While being treated with thiamine, none of the patients experienced an acute metabolic decompensation. One patient experienced an encephalopathic episode after discontinuing thiamine. Thiamine therapy did not improve peripheral axonal neuropathy in the 7 patients who had this clinical feature. However, in 2 patients who were treated early, peripheral neuropathy did not occur, suggesting a possible preventative effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33544541" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Samur, B. M., Gumus, G., Canpolat, M., Gumus, H., Per, H., Caglayan, A. O. <strong>Clinical and genetic studies of thiamine metabolism dysfunction syndrome-4: case series and review of the literature.</strong> Clin. Dysmorph. 31: 125-131, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35102031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35102031</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35102031[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1097/MCD.0000000000000411" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35102031">Samur et al. (2022)</a> reported outcomes in 2 symptomatic patients with THMD4 who were treated with thiamine. Patient 1 demonstrated an improvement in symptoms including axonal neuropathy and febrile episodes. Patient 2 was treated with both thiamine and baclofen and had improvement in his febrile episodes as well as achieving seizure control. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35102031" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>By homozygosity mapping followed by candidate gene analysis of a consanguineous Arab Muslim family with bilateral striatal necrosis and progressive polyneuropathy, <a href="#7" class="mim-tip-reference" title="Spiegel, R., Shaag, A., Edvardson, S., Mandel, H., Stepensky, P., Shalev, S. A., Horovitz, Y., Pines, O., Elpeleg, O. <strong>SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis.</strong> Ann. Neurol. 66: 419-424, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19798730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19798730</a>] [<a href="https://doi.org/10.1002/ana.21752" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19798730">Spiegel et al. (2009)</a> identified a homozygous mutation in the SLC25A19 gene (G125S; <a href="/entry/606521#0002">606521.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19798730" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In an Italian patient, born to consanguineous parents, <a href="#1" class="mim-tip-reference" title="Bottega, R., Perrone, M. D., Vecchiato, K., Taddio, A., Sabui, S., Pecile, V., Said, H. M., Faletra, F. <strong>Functional analysis of the third identified SLC25A19 mutation causative for the thiamine metabolism dysfunction syndrome 4.</strong> J. Hum. Genet. 64: 1075-1081, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31506564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31506564</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31506564[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1038/s10038-019-0666-5" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31506564">Bottega et al. (2019)</a> identified a homozygous mutation in the SLC25A19 gene (Q192H; <a href="/entry/606521#0003">606521.0003</a>). SLC25A19 with the Q192H mutation in HepG2 cells showed reduced expression in mitochondrial and whole cell homogenates compared to wildtype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31506564" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 unrelated Indian children, born to consanguineous parents, with THMD4, <a href="#3" class="mim-tip-reference" title="Gowda, V. K., Srinivasan, V. M., Jehta, K., Bhat, M. D. <strong>Bilateral striatal necrosis with polyneuropathy with a novel SLC25A19 (mitochondrial thiamine pyrophosphate carrier OMIM*606521) mutation: treatable thiamine metabolic disorder--a report of two Indian cases.</strong> Neuropediatrics 50: 313-317, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31295743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31295743</a>] [<a href="https://doi.org/10.1055/s-0039-1693148" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31295743">Gowda et al. (2019)</a> identified homozygous missense mutations in the SLC25A19 gene (E304K, <a href="/entry/606521#0004">606521.0004</a>; L290Q, <a href="/entry/606521#0005">606521.0005</a>). The mutations, which were found by next-generation sequencing and confirmed by Sanger sequencing, were identified in heterozygous state in both sets of parents. Functional studies were not performed. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31295743" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Li, D., Song, J., Li, X., Liu, Y., Dong, H., Kang, L., Liu, Y., Zhang, Y., Jin, Y., Guan, H., Zhou, C., Yang, Y. <strong>Eleven novel mutations and clinical characteristics in seven Chinese patients with thiamine metabolism dysfunction syndrome.</strong> Europ. J. Med. Genet. 63: 104003, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32679198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32679198</a>] [<a href="https://doi.org/10.1016/j.ejmg.2020.104003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32679198">Li et al. (2020)</a> identified compound heterozygous mutations in the SLC25A19 gene in 2 patients with THMD4: A65V and P152T (patient 5) and A161T and A184P (patient 6). The mutations, which were identified by whole-exome sequencing and confirmed by Sanger sequencing, were identified in the carrier state in the parents. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32679198" 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="Chen, Y., Fang, B., Hu, X., Guo, R., Guo, J., Fang, K., Ni, J., Li, W., Qian, S., Hao, C. <strong>Identification and functional analysis of novel SLC25A19 variants causing thiamine metabolism dysfunction syndrome 4.</strong> Orphanet J. Rare Dis. 16: 403, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34587972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34587972</a>] [<a href="https://doi.org/10.1186/s13023-021-02028-4" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34587972">Chen et al. (2021)</a> identified compound heterozygous mutations in the SLC25A19 gene in 2 Chinese sibs (G26R, <a href="/entry/606521#0006">606521.0006</a> and F249I, <a href="/entry/606521#0007">606521.0007</a>) and an unrelated Chinese child (A57T and A128V) with THMD4. Transfection of each mutation into HEK293 resulted in decreased mitochondrial thiamine pyrophosphate (TPP) compared to wildtype, indicative of deficient TPP transport. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34587972" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In 2 Turkish brothers and an unrelated Turkish patient with THMD4, <a href="#6" class="mim-tip-reference" title="Samur, B. M., Gumus, G., Canpolat, M., Gumus, H., Per, H., Caglayan, A. O. <strong>Clinical and genetic studies of thiamine metabolism dysfunction syndrome-4: case series and review of the literature.</strong> Clin. Dysmorph. 31: 125-131, 2022.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35102031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35102031</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35102031[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1097/MCD.0000000000000411" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="35102031">Samur et al. (2022)</a> identified homozygosity for a previously reported missense mutation in the SLC25A19 gene (Q192H; <a href="/entry/606521#0003">606521.0003</a>). The mutation was identified by whole-exome sequencing and confirmed by Sanger sequencing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35102031" 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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Bottega, R., Perrone, M. D., Vecchiato, K., Taddio, A., Sabui, S., Pecile, V., Said, H. M., Faletra, F.
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<strong>Functional analysis of the third identified SLC25A19 mutation causative for the thiamine metabolism dysfunction syndrome 4.</strong>
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J. Hum. Genet. 64: 1075-1081, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31506564/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31506564</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=31506564[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31506564" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1038/s10038-019-0666-5" target="_blank">Full Text</a>]
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Chen, Y., Fang, B., Hu, X., Guo, R., Guo, J., Fang, K., Ni, J., Li, W., Qian, S., Hao, C.
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<strong>Identification and functional analysis of novel SLC25A19 variants causing thiamine metabolism dysfunction syndrome 4.</strong>
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Orphanet J. Rare Dis. 16: 403, 2021.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34587972/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34587972</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34587972" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1186/s13023-021-02028-4" target="_blank">Full Text</a>]
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Gowda, V. K., Srinivasan, V. M., Jehta, K., Bhat, M. D.
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<strong>Bilateral striatal necrosis with polyneuropathy with a novel SLC25A19 (mitochondrial thiamine pyrophosphate carrier OMIM*606521) mutation: treatable thiamine metabolic disorder--a report of two Indian cases.</strong>
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Neuropediatrics 50: 313-317, 2019.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31295743/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31295743</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31295743" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1055/s-0039-1693148" target="_blank">Full Text</a>]
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Li, D., Song, J., Li, X., Liu, Y., Dong, H., Kang, L., Liu, Y., Zhang, Y., Jin, Y., Guan, H., Zhou, C., Yang, Y.
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<strong>Eleven novel mutations and clinical characteristics in seven Chinese patients with thiamine metabolism dysfunction syndrome.</strong>
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Europ. J. Med. Genet. 63: 104003, 2020.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32679198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32679198</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32679198" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ejmg.2020.104003" target="_blank">Full Text</a>]
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Porta, F., Siri, B., Chiesa, N., Ricci, F., Nika, L., Sciortino, P., Spada, M.
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<strong>SLC25A19 deficiency and bilateral striatal necrosis with polyneuropathy: a new case and review of the literature.</strong>
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J. Pediat. Endocr. Metab. 34: 261-266, 2021.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33544541/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33544541</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33544541" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Samur, B. M., Gumus, G., Canpolat, M., Gumus, H., Per, H., Caglayan, A. O.
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<strong>Clinical and genetic studies of thiamine metabolism dysfunction syndrome-4: case series and review of the literature.</strong>
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Clin. Dysmorph. 31: 125-131, 2022.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/35102031/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">35102031</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=35102031[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=35102031" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1097/MCD.0000000000000411" target="_blank">Full Text</a>]
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Spiegel, R., Shaag, A., Edvardson, S., Mandel, H., Stepensky, P., Shalev, S. A., Horovitz, Y., Pines, O., Elpeleg, O.
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<strong>SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis.</strong>
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Ann. Neurol. 66: 419-424, 2009.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19798730/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19798730</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19798730" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/ana.21752" target="_blank">Full Text</a>]
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Hilary J. Vernon - updated : 08/26/2022
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Hilary J. Vernon - updated : 07/08/2022
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Cassandra L. Kniffin : 1/24/2011
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alopez : 04/09/2024
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carol : 08/29/2022<br>carol : 08/26/2022<br>carol : 07/08/2022<br>carol : 02/10/2012<br>ckniffin : 2/8/2012<br>terry : 3/3/2011<br>wwang : 2/16/2011<br>ckniffin : 1/24/2011
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<strong>#</strong> 613710
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THIAMINE METABOLISM DYSFUNCTION SYNDROME 4 (BILATERAL STRIATAL DEGENERATION AND PROGRESSIVE POLYNEUROPATHY TYPE); THMD4
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BILATERAL STRIATAL DEGENERATION AND PROGRESSIVE POLYNEUROPATHY<br />
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STRIATAL NECROSIS, BILATERAL, AND PROGRESSIVE POLYNEUROPATHY
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<strong>SNOMEDCT:</strong> 771305006;
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<strong>ORPHA:</strong> 217396;
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17q25.1
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Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type)
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613710
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Autosomal recessive
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606521
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<p>A number sign (#) is used with this entry because thiamine metabolism dysfunction syndrome-4 (THMD4), also known as bilateral striatal degeneration and progressive polyneuropathy, is caused by homozygous or compound heterozygous mutation in the SLC25A19 gene (606521) on chromosome 17q25.</p><p>Amish lethal microcephaly (MCPHA; 607196) is an allelic disorder with a more severe phenotype.</p>
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<p>Thiamine metabolism dysfunction syndrome-4 (THMD4) is an autosomal recessive metabolic disorder characterized by childhood onset of episodic encephalopathy, often associated with a febrile illness, and causing transient neurologic dysfunction. Most patients recover fully, but some may have mild residual weakness. Affected individuals also develop a slowly progressive axonal polyneuropathy beginning in childhood. Brain imaging during the acute episodes shows lesions consistent with bilateral striatal degeneration or necrosis (summary by Spiegel et al., 2009). </p><p>For a discussion of genetic heterogeneity of disorders due to thiamine metabolism dysfunction, see THMD1 (249270).</p>
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<p>Spiegel et al. (2009) reported a consanguineous Arab Muslim family in which 4 sibs had a disorder characterized by acute encephalopathic episodes associated with striatal necrosis on brain imaging as well as a progressive chronic polyneuropathy. All patients had normal early psychomotor development, with onset of episodic acute encephalopathic episodes in childhood between ages 3.5 and 6.5 years. These episodes were associated with nonspecific febrile illness and were characterized by lethargy, muscle weakness resulting in paralysis, areflexia, and dysarthria. These episodes were followed by complete resolution and no loss of psychomotor development, although most had residual mild distal weakness. Laboratory investigations showed mild increased lactate in the cerebrospinal fluid (CSF) during the acute phase, and brain imaging showed bilateral multiple T2-hyperintense lesions in the caudate and putamen, with sparing of the globus pallidus. In addition to encephalopathic episodes, all sibs had childhood onset of progressive chronic polyneuropathy characterized by motor difficulties, frequent falls, and distal weakness and atrophy of the lower limbs, accompanied by lower limb contractures and foot deformities. Electrophysiologic studies showed an axonal motor neuropathy. All sibs had age-appropriate cognition at ages 7 to 20 years. </p><p>Bottega et al. (2019) reported a patient who had a history of neurologic impairment due to acute encephalopathic events in the setting of fevers at 1 year of age. The events were characterized by tremor, hypotonia, gait difficulties, dysphagia, dysphonia, and altered consciousness. At 18 years of age, he had moderate cognitive delay, pes cavus, and atrophy of the interosseous muscles. Electromyography showed a motor and sensory neuropathy. Brain MRI showed abnormal signal in the caudate nucleus, putamen, and insula cortex. </p><p>Gowda et al. (2019) reported clinical features in a 36-month-old boy and a 5-year-old girl. The boy presented with acute weakness and encephalopathy in the setting of gastroenteritis at 11 months of age. He recovered after 3 months, but at 23 months of age and 33 months of age he had recurrent episodes of acute encephalopathy. After initiation of oral thiamine, he regained lost developmental milestones. Brain MRI showed hyperintensity of the bilateral basal ganglia and thalami. Nerve conduction studies showed axonal neuropathy. Laboratory tests demonstrated elevated serum lactate. The girl presented at 16 months of age with encephalopathy in the setting of a febrile illness. She had incomplete recovery but had another episode of encephalopathy with febrile illness at 2 years and 6 months of age. Brain MRI at 16 months of age showed hyperintensity in the basal ganglia and thalami. Nerve conduction testing showed an axonal neuropathy, which improved after thiamine supplementation. </p><p>Li et al. (2020) described 2 patients with recurrent encephalopathic episodes, abnormal signal in the putamen and caudate nucleus on brain MRI, and elevated alpha-ketoglutarate in the urine. Patient 5, aged 2 years and 10 months, and patient 6, aged 2 years and 3 months, had normal intelligence and slight motor developmental delay. </p><p>Chen et al. (2021) reported 2 sibs (patients 2 and 3) who presented with coma in the setting of influenza A infection. Brain MRI in both sibs showed abnormal signal in the basal ganglia. Both patients required mechanical ventilation but recovered spontaneous respiration. Three months after discharge and despite being started on oral thiamine, both sibs had high muscle tone, absence of speech, and occasional gaze towards sound. </p><p>Samur et al. (2022) reported 3 patients with episodic encephalopathy, abnormal gait, and polyneuropathy. Patients 1 and 2 were 11- and 13-year-old brothers, respectively. Patient 1 began having encephalopathic episodes at 2 years of age. The episodes subsequently occurred every 2 to 3 years and were triggered by respiratory tract infections. He also had dysarthria, muscle weakness, ataxia and pes equinovarus. Brain MRI showed white matter hyperintensities and necrotic degeneration of the caudate, putamen, and thalamus. Patient 2 additionally had dysphonia, seizures, muscle weakness, and areflexia. His brain MRI showed degenerative changes in the bilateral caudate nuclei. Patient 3 was a 16-year-old girl who began having encephalopathic episodes at 4 years of age. She also had ataxia, increased muscle tone, and pes equinovarus. Brain MRI showed bilateral striatal necrosis. </p>
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<p>The transmission pattern of THMD4 in the consanguineous family reported by Spiegel et al. (2009) was consistent with autosomal recessive inheritance. </p>
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<p>Porta et al. (2021) described response to thiamine treatment in 9 patients with THMD4, 8 of whom had previously been reported. Metabolic decompensations were recurrent and triggered by febrile episodes in the patients prior to thiamine treatment. While being treated with thiamine, none of the patients experienced an acute metabolic decompensation. One patient experienced an encephalopathic episode after discontinuing thiamine. Thiamine therapy did not improve peripheral axonal neuropathy in the 7 patients who had this clinical feature. However, in 2 patients who were treated early, peripheral neuropathy did not occur, suggesting a possible preventative effect. </p><p>Samur et al. (2022) reported outcomes in 2 symptomatic patients with THMD4 who were treated with thiamine. Patient 1 demonstrated an improvement in symptoms including axonal neuropathy and febrile episodes. Patient 2 was treated with both thiamine and baclofen and had improvement in his febrile episodes as well as achieving seizure control. </p>
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<strong>Molecular Genetics</strong>
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<p>By homozygosity mapping followed by candidate gene analysis of a consanguineous Arab Muslim family with bilateral striatal necrosis and progressive polyneuropathy, Spiegel et al. (2009) identified a homozygous mutation in the SLC25A19 gene (G125S; 606521.0002). </p><p>In an Italian patient, born to consanguineous parents, Bottega et al. (2019) identified a homozygous mutation in the SLC25A19 gene (Q192H; 606521.0003). SLC25A19 with the Q192H mutation in HepG2 cells showed reduced expression in mitochondrial and whole cell homogenates compared to wildtype. </p><p>In 2 unrelated Indian children, born to consanguineous parents, with THMD4, Gowda et al. (2019) identified homozygous missense mutations in the SLC25A19 gene (E304K, 606521.0004; L290Q, 606521.0005). The mutations, which were found by next-generation sequencing and confirmed by Sanger sequencing, were identified in heterozygous state in both sets of parents. Functional studies were not performed. </p><p>Li et al. (2020) identified compound heterozygous mutations in the SLC25A19 gene in 2 patients with THMD4: A65V and P152T (patient 5) and A161T and A184P (patient 6). The mutations, which were identified by whole-exome sequencing and confirmed by Sanger sequencing, were identified in the carrier state in the parents. </p><p>Chen et al. (2021) identified compound heterozygous mutations in the SLC25A19 gene in 2 Chinese sibs (G26R, 606521.0006 and F249I, 606521.0007) and an unrelated Chinese child (A57T and A128V) with THMD4. Transfection of each mutation into HEK293 resulted in decreased mitochondrial thiamine pyrophosphate (TPP) compared to wildtype, indicative of deficient TPP transport. </p><p>In 2 Turkish brothers and an unrelated Turkish patient with THMD4, Samur et al. (2022) identified homozygosity for a previously reported missense mutation in the SLC25A19 gene (Q192H; 606521.0003). The mutation was identified by whole-exome sequencing and confirmed by Sanger sequencing. </p>
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<strong>REFERENCES</strong>
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Bottega, R., Perrone, M. D., Vecchiato, K., Taddio, A., Sabui, S., Pecile, V., Said, H. M., Faletra, F.
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<strong>Functional analysis of the third identified SLC25A19 mutation causative for the thiamine metabolism dysfunction syndrome 4.</strong>
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J. Hum. Genet. 64: 1075-1081, 2019.
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[PubMed: 31506564]
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[Full Text: https://doi.org/10.1038/s10038-019-0666-5]
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Chen, Y., Fang, B., Hu, X., Guo, R., Guo, J., Fang, K., Ni, J., Li, W., Qian, S., Hao, C.
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<strong>Identification and functional analysis of novel SLC25A19 variants causing thiamine metabolism dysfunction syndrome 4.</strong>
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Orphanet J. Rare Dis. 16: 403, 2021.
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[PubMed: 34587972]
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[Full Text: https://doi.org/10.1186/s13023-021-02028-4]
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Gowda, V. K., Srinivasan, V. M., Jehta, K., Bhat, M. D.
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<strong>Bilateral striatal necrosis with polyneuropathy with a novel SLC25A19 (mitochondrial thiamine pyrophosphate carrier OMIM*606521) mutation: treatable thiamine metabolic disorder--a report of two Indian cases.</strong>
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Neuropediatrics 50: 313-317, 2019.
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[PubMed: 31295743]
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[Full Text: https://doi.org/10.1055/s-0039-1693148]
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Li, D., Song, J., Li, X., Liu, Y., Dong, H., Kang, L., Liu, Y., Zhang, Y., Jin, Y., Guan, H., Zhou, C., Yang, Y.
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<strong>Eleven novel mutations and clinical characteristics in seven Chinese patients with thiamine metabolism dysfunction syndrome.</strong>
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Europ. J. Med. Genet. 63: 104003, 2020.
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[PubMed: 32679198]
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[Full Text: https://doi.org/10.1016/j.ejmg.2020.104003]
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Porta, F., Siri, B., Chiesa, N., Ricci, F., Nika, L., Sciortino, P., Spada, M.
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<strong>SLC25A19 deficiency and bilateral striatal necrosis with polyneuropathy: a new case and review of the literature.</strong>
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[PubMed: 33544541]
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Samur, B. M., Gumus, G., Canpolat, M., Gumus, H., Per, H., Caglayan, A. O.
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<strong>Clinical and genetic studies of thiamine metabolism dysfunction syndrome-4: case series and review of the literature.</strong>
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Clin. Dysmorph. 31: 125-131, 2022.
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[PubMed: 35102031]
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[Full Text: https://doi.org/10.1097/MCD.0000000000000411]
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Spiegel, R., Shaag, A., Edvardson, S., Mandel, H., Stepensky, P., Shalev, S. A., Horovitz, Y., Pines, O., Elpeleg, O.
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<strong>SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis.</strong>
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Ann. Neurol. 66: 419-424, 2009.
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[PubMed: 19798730]
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[Full Text: https://doi.org/10.1002/ana.21752]
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Hilary J. Vernon - updated : 08/26/2022<br>Hilary J. Vernon - updated : 07/08/2022
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