3284 lines
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3284 lines
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Entry
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- #607483 - BASAL GANGLIA DISEASE, BIOTIN-THIAMINE RESPONSIVE; BTBGD
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- OMIM
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<p>
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<span class="h4">#607483</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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<li role="presentation">
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<a href="/clinicalSynopsis/607483"><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="#diagnosis">Diagnosis</a>
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<a href="#clinicalManagement">Clinical Management</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#mapping">Mapping</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#populationGenetics">Population Genetics</a>
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<a href="#animalModel">Animal Model</a>
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<li role="presentation">
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<a href="#references"><strong>References</strong></a>
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<li role="presentation">
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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</li>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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</li>
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</ul>
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<div class="col-lg-2 col-lg-push-8 col-md-2 col-md-push-8 col-sm-2 col-sm-push-8 col-xs-12">
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<div style="display: table-cell;">External Links</div>
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</div>
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</a>
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</h4>
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</div>
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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><a href="https://clinicaltrials.gov/search?cond=BASAL GANGLIA DISEASE, BIOTIN-THIAMINE RESPONSIVE" 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="#mimEuroGentestFold" id="mimEuroGentestToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A list of European laboratories that offer genetic testing."><span id="mimEuroGentestToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>EuroGentest</div>
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<div id="mimEuroGentestFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=18407&Typ=Pat" title="Thiamine-responsive encephalopathy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Thiamine-responsive enceph… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=20049&Typ=Pat" title="Infantile spasms-psychomotor retardation-progressive brain atrophy-basal ganglia disease syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Infantile spasms-psychomot… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=10866&Typ=Pat" title="Biotin-thiamine-responsive basal ganglia disease" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Biotin-thiamine-responsive… </a></div>
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</div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK169615/" 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/756" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://medlineplus.gov/genetics/condition/biotin-thiamine-responsive-basal-ganglia-disease" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=607483[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="#mimOrphanetFold" id="mimOrphanetToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="European reference portal for information on rare diseases and orphan drugs."><span id="mimOrphanetToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Orphanet</div>
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<div id="mimOrphanetFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=199348" title="Thiamine-responsive encephalopathy" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Thiamine-responsive enceph…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=263410" title="Infantile spasms-psychomotor retardation-progressive brain atrophy-basal ganglia disease syndrome" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Infantile spasms-psychomot…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=65284" title="Biotin-thiamine-responsive basal ganglia disease" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Biotin-thiamine-responsive…</a></div>
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</div>
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</div>
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<div class="panel panel-default" style="margin-top: 0px; border-radius: 0px">
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div style="display: table-cell;">Animal Models</div>
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/disease/DOID:0050659" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="http://www.informatics.jax.org/disease/607483" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://omia.org/OMIA001097/" class="mim-tip-hint" title="Online Mendelian Inheritance in Animals (OMIA) is a database of genes, inherited disorders and traits in 191 animal species (other than human and mouse.)" target="_blank">OMIA</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0050659" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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</div>
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</div>
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<span>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</div>
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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<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> 703522009<br />
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<strong>ORPHA:</strong> 199348, 263410, 65284<br />
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<strong>DO:</strong> 0050659<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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607483
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</span>
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</span>
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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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BASAL GANGLIA DISEASE, BIOTIN-THIAMINE RESPONSIVE; BTBGD
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</h3>
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</div>
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<div>
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<br />
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<a id="alternativeTitles" class="mim-anchor"></a>
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<em>Alternative titles; symbols</em>
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<div>
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<h4>
|
|
<span class="mim-font">
|
|
THIAMINE METABOLISM DYSFUNCTION SYNDROME 2 (BIOTIN- AND THIAMINE-RESPONSIVE TYPE); THMD2<br />
|
|
BASAL GANGLIA DISEASE, BIOTIN-RESPONSIVE; BBGD<br />
|
|
ENCEPHALOPATHY, THIAMINE-RESPONSIVE
|
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</span>
|
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</h4>
|
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
|
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<a id="phenotypeMap" class="mim-anchor"></a>
|
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<h4>
|
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<span class="mim-font">
|
|
<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">
|
|
<thead>
|
|
<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>
|
|
Inheritance
|
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</th>
|
|
<th>
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Phenotype <br /> mapping key
|
|
</th>
|
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<th>
|
|
Gene/Locus
|
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</th>
|
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<th>
|
|
Gene/Locus <br /> MIM number
|
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</th>
|
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</tr>
|
|
</thead>
|
|
<tbody>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/geneMap/2/1075?start=-3&limit=10&highlight=1075">
|
|
2q36.3
|
|
</a>
|
|
</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
|
Thiamine metabolism dysfunction syndrome 2 (biotin/thiamine-responsive basal ganglia disease type)
|
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|
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</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/607483"> 607483 </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>
|
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|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
SLC19A3
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606152"> 606152 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/607483" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
|
|
<a href="/phenotypicSeries/PS249270" class="btn btn-info" role="button"> Phenotypic Series </a>
|
|
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-info dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimPhenotypicSeriesFold" onclick="ga('send', 'event', 'Unfurl', 'PhenotypicSeries', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/607483" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/607483" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
|
</ul>
|
|
</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
|
|
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|
|
|
|
|
<div>
|
|
<p />
|
|
</div>
|
|
|
|
|
|
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
<div>
|
|
<span class="mim-font">
|
|
|
|
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Face </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Facial dystonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1851915&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1851915</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012179" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012179</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0012179" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0012179</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Eyes </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Nystagmus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/563001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">563001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H55.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H55.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/379.50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">379.50</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0028738&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0028738</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000639" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000639</a>]</span><br /> -
|
|
External ophthalmoplegia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/19373007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">19373007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H49.88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H49.88</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/378.55" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">378.55</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0162292&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0162292</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000544" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000544</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000544" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000544</a>]</span><br /> -
|
|
Ptosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/11934000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">11934000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/29696001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">29696001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.409" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.409</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.40</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/374.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">374.3</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/374.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">374.30</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0005745&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0005745</a>, <a href="https://bioportal.bioontology.org/search?q=C0033377&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0033377</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000508</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000508</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=76abf29563d4adc64d21da86221224b1" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Ptosis-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=76abf29563d4adc64d21da86221224b1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
|
|
Gaze palsy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1112261&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1112261</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ABDOMEN </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Gastrointestinal </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Dysphagia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/288939007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">288939007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/40739000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">40739000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R13.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R13.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R13.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R13.10</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/787.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.2</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/787.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011168&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011168</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002015" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002015</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002015" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002015</a>]</span><br /> -
|
|
Swallowing difficulties <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/288939007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">288939007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/40739000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">40739000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R13.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R13.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R13.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R13.10</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/787.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.2</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/787.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011168&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011168</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002015" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002015</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002015" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002015</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">
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<strong> NEUROLOGIC </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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<div>
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<span class="h5 mim-font">
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<em> Central Nervous System </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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- Encephalopathy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/81308009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">81308009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G93.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G93.40</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/348.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">348.30</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/348.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">348.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0085584&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085584</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001298" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001298</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001298" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001298</a>]</span><br /> -
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Psychomotor retardation (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398991009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398991009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1144814003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1144814003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0424230&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424230</a>, <a href="https://bioportal.bioontology.org/search?q=C5441816&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5441816</a>]</span><br /> -
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Dystonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/15802004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">15802004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G24.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G24.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/G24" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G24</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013421</a>, <a href="https://bioportal.bioontology.org/search?q=C0393593&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0393593</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001332" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001332</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001332" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001332</a>]</span><br /> -
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Seizures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91175000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91175000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span><br /> -
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Confusion <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/40917007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">40917007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/286933003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">286933003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R41.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R41.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0009676&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009676</a>, <a href="https://bioportal.bioontology.org/search?q=C0683369&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0683369</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001289" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001289</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001289" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001289</a>]</span><br /> -
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Irritability <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/55929007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">55929007</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/799.22" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">799.22</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0022107&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022107</a>, <a href="https://bioportal.bioontology.org/search?q=C2700617&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2700617</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000737" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000737</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000737" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000737</a>]</span><br /> -
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Axial hypotonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853743&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853743</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008936" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008936</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008936" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008936</a>]</span><br /> -
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Extremity hypertonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749427&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749427</a>]</span><br /> -
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Extensor plantar responses <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246586009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246586009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/366575004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">366575004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0034935&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0034935</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003487" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003487</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003487" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003487</a>]</span><br /> -
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Gait ataxia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/25136009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">25136009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R26.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R26.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0751837&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0751837</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002066" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002066</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002066" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002066</a>]</span><br /> -
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Inability to walk <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/282145008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">282145008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0560046&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0560046</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002540" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002540</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002540" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002540</a>]</span><br /> -
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Paraparesis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1845001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1845001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G82.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G82.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0221166&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0221166</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002385" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002385</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002385" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002385</a>]</span><br /> -
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Rigidity <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/16046003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">16046003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0700109&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0700109</a>, <a href="https://bioportal.bioontology.org/search?q=C0026837&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026837</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002063" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002063</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002063" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002063</a>]</span><br /> -
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Dysarthria <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/8011004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">8011004</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.13" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.13</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/784.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">784.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001260" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001260</a>]</span><br /> -
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Mutism <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/88052002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">88052002</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026884&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026884</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002300" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002300</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002300" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002300</a>]</span><br /> -
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Pyramidal signs <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/14648003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">14648003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0234132&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0234132</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007256" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007256</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0007256" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0007256</a>]</span><br /> -
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Coma <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/371632003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">371632003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405809000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405809000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R40.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R40.20</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R40.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R40.2</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/780.01" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">780.01</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0543874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0543874</a>, <a href="https://bioportal.bioontology.org/search?q=C3146279&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3146279</a>, <a href="https://bioportal.bioontology.org/search?q=C0009421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009421</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001259" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001259</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001259" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001259</a>]</span><br /> -
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Basal ganglia lesions seen on MRI <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4013026&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4013026</a>]</span><br /> -
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Cortical and subcortical hyperintensities <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3149362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3149362</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">
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<strong> MISCELLANEOUS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Variable age at onset (birth to adolescence)<br /> -
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May be precipitated by minor illness (e.g., viral infection, fever)<br /> -
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Responsive to high-dose biotin or biotin/thiamine treatment<br /> -
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Dystonia and seizures may persist after resolution of episodes<br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MOLECULAR BASIS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Caused by mutation in the solute carrier family 19, folate transporter, member 3 gene (SLC19A3, <a href="/entry/606152#0001">606152.0001</a>)<br />
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</span>
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</div>
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</div>
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</div>
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<div class="text-right">
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
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</div>
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</div>
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</div>
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<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
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<div class="small">
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<div class="row">
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<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
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<h5>
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Thiamine-responsive dysfunction syndrome
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- <a href="/phenotypicSeries/PS249270">PS249270</a>
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- 5 Entries
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</h5>
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</div>
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</div>
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<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
|
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<table class="table table-bordered table-condensed table-hover mim-table-padding">
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<thead>
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<tr>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
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<strong>Location</strong>
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</th>
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<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
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<strong>Phenotype</strong>
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</th>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
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<strong>Inheritance</strong>
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</th>
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
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<strong>Phenotype<br />mapping key</strong>
|
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</th>
|
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
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<strong>Phenotype<br />MIM number</strong>
|
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</th>
|
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<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
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<strong>Gene/Locus</strong>
|
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</th>
|
|
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
|
|
<strong>Gene/Locus<br />MIM number</strong>
|
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</th>
|
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</tr>
|
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</thead>
|
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<tbody>
|
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|
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<tr>
|
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<td>
|
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<span class="mim-font">
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<a href="/geneMap/1/1403?start=-3&limit=10&highlight=1403"> 1q24.2 </a>
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/249270"> Thiamine-responsive megaloblastic anemia syndrome </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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|
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
|
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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|
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/249270"> 249270 </a>
|
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</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/603941"> SLC19A2 </a>
|
|
</span>
|
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</td>
|
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/603941"> 603941 </a>
|
|
</span>
|
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</td>
|
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</tr>
|
|
|
|
<tr>
|
|
<td>
|
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<span class="mim-font">
|
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<a href="/geneMap/2/1075?start=-3&limit=10&highlight=1075"> 2q36.3 </a>
|
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|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
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<a href="/entry/607483"> Thiamine metabolism dysfunction syndrome 2 (biotin/thiamine-responsive basal ganglia disease type) </a>
|
|
</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>
|
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</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606152"> SLC19A3 </a>
|
|
</span>
|
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</td>
|
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<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606152"> 606152 </a>
|
|
</span>
|
|
</td>
|
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</tr>
|
|
|
|
<tr>
|
|
<td>
|
|
<span class="mim-font">
|
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|
|
<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">
|
|
|
|
<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/607196"> 607196 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606521"> SLC25A19 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606521"> 606521 </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/613710"> Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy 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/613710"> 613710 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606521"> SLC25A19 </a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/606521"> 606521 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
|
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|
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|
|
<div class="text-right small">
|
|
<a href="#mimPhenotypicSeriesFold" data-toggle="collapse">▲ Close</a>
|
|
</div>
|
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</div>
|
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</div>
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</div>
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<div>
|
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<br />
|
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</div>
|
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<div>
|
|
<a id="text" class="mim-anchor"></a>
|
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
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|
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<span class="mim-font">
|
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
|
|
<strong>TEXT</strong>
|
|
</span>
|
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</span>
|
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</h4>
|
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<div id="mimTextFold" class="collapse in ">
|
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<span class="mim-text-font">
|
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<p>A number sign (#) is used with this entry because biotin-thiamine-responsive basal ganglia disease (BTBGD), also known as metabolism dysfunction syndrome-2 (THMD2) or thiamine-responsive encephalopathy, is caused by homozygous or compound heterozygous mutation in the SLC19A3 gene (<a href="/entry/606152">606152</a>), which encodes a thiamine transporter, on chromosome 2q36.</p>
|
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</span>
|
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<div>
|
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<br />
|
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</div>
|
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</div>
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<div>
|
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<a id="description" class="mim-anchor"></a>
|
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<h4 href="#mimDescriptionFold" id="mimDescriptionToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
|
|
<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
|
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<span class="mim-font">
|
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<strong>Description</strong>
|
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</span>
|
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</h4>
|
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</div>
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<div id="mimDescriptionFold" class="collapse in ">
|
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<span class="mim-text-font">
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<p>Biotin-thiamine-responsive basal ganglia disease (BTBGD), also known as metabolism dysfunction syndrome-2 (THMD2) or thiamine-responsive encephalopathy, is an autosomal recessive metabolic disorder characterized by episodic encephalopathy, often triggered by febrile illness, presenting as confusion, seizures, external ophthalmoplegia, dysphagia, and sometimes coma and death. Administration of high doses of biotin, and sometimes thiamine, during these crises results in partial or complete improvement within days. If untreated, encephalopathies can result in permanent dystonia. Brain imaging may show characteristic bilateral lesions of the basal ganglia. It is not known why biotin administration results in clinical improvement, as the molecular basis of the disorder is mutation in a gene encoding a thiamine transporter. However, biotin may increase the gene expression of SLC19A3 (summary by <a href="#1" class="mim-tip-reference" title="Debs, R., Depienne, C., Rastetter, A., Bellanger, A., Degos, B., Galanaud, D., Keren, B., Lyon-Caen, O., Brice, A., Sedel, F. <strong>Biotin-responsive basal ganglia disease in ethnic Europeans with novel SLC19A3 mutations.</strong> Arch. Neurol. 67: 126-130, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20065143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20065143</a>] [<a href="https://doi.org/10.1001/archneurol.2009.293" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20065143">Debs et al., 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20065143" 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="#10" class="mim-tip-reference" title="Ozand, P. T., Gascon, G. G., Al Essa, M., Joshi, S., Al Jishi, E., Bakheet, S., Al Watban, J., Al-Kawi, M. Z., Dabbagh, O. <strong>Biotin-responsive basal ganglia disease: a novel entity.</strong> Brain 121: 1267-1279, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9679779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9679779</a>] [<a href="https://doi.org/10.1093/brain/121.7.1267" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9679779">Ozand et al. (1998)</a> described a biotin-responsive basal ganglia disease in 10 patients, 8 of whom were Saudi, 1 Syrian, and 1 of Yemen origin. The parents in all cases were consanguineous, being first cousins in 7 of the 10. In 1 family with first-cousin parents, 2 sisters were affected and 4 of their sibs, 2 boys and 2 girls, had died of a similar disease without diagnosis. Presentation ranged from 1 to 14 years. The disease appeared at onset as a subacute encephalopathy, with confusion, dysarthria, and dysphagia and occasional supranuclear facial nerve palsy or external ophthalmoplegia, and progressed to severe cogwheel rigidity, dystonia, and quadriparesis. These symptoms disappeared within a few days if biotin (5-10 mg/kg/day) was administered, and there were no neurologic sequelae. Symptoms reappeared within 1 month if biotin was discontinued. Patients diagnosed late, or who had had repeat episodes, suffered from residual symptoms such as paraparesis, mild mental retardation, or dystonia. Biochemical studies of intermediary metabolism, autoimmune toxicologic studies, enzyme assays including those for biotinidase (<a href="/entry/609019">609019</a>), carboxylase, and lysosomal activities, and bacterial and viral studies were all normal. The etiology was thought to be related to a defect in the transporter of biotin across the blood-brain barrier. The only consistent radiologic abnormality was central necrosis of the head of the caudate bilaterally and complete, or partial, involvement of the putamen on brain MRI. This finding was present during the initial acute encephalopathy and remained unchanged during follow-up of 3 to 10 years. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9679779" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#14" class="mim-tip-reference" title="Zeng, W.-Q., Al-Yamani, E., Acierno, J. S., Jr., Slaugenhaupt, S., Gillis, T., MacDonald, M. E., Ozand, P. T., Gusella, J. F. <strong>Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3.</strong> Am. J. Hum. Genet. 77: 16-26, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15871139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15871139</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15871139[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/431216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15871139">Zeng et al. (2005)</a> stated that all patients with biotin-responsive basal ganglia disease diagnosed to that time were of Saudi, Syrian, or Yemeni ancestry, and all had consanguineous parents. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15871139" 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="Debs, R., Depienne, C., Rastetter, A., Bellanger, A., Degos, B., Galanaud, D., Keren, B., Lyon-Caen, O., Brice, A., Sedel, F. <strong>Biotin-responsive basal ganglia disease in ethnic Europeans with novel SLC19A3 mutations.</strong> Arch. Neurol. 67: 126-130, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20065143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20065143</a>] [<a href="https://doi.org/10.1001/archneurol.2009.293" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20065143">Debs et al. (2010)</a> reported a Portuguese brother and sister with biotin-responsive basal ganglia disease. At age 7 years, the brother developed a progressive subacute encephalopathy with confusion, inability to walk, loss of speech, swallowing dysfunction, and generalized seizures after a benign illness. He recovered, but had residual dystonia, seizures, and pyramidal signs associated with signal abnormalities of the putamen and caudate. At age 33, he again presented with subacute neurologic deterioration characterized by with confusion, severe gait ataxia, mutism, swallowing dysfunction, gaze palsy, and bilateral ptosis. Brain MRI showed diffuse signal abnormalities in cortical and subcortical areas, thalami, and mesencephalon. Treatment with high-dose biotin (600 mg/day) resulted in improvement of clinical features and disappearance of signal abnormalities on follow-up MRI. His sister developed simple partial motor seizures of the right upper limb at age 12 years. At age 20, she had subacute neurologic deterioration with generalized seizures, loss of ambulation, swallowing dysfunction, and dysarthria. She recovered but had residual dystonia of the face and upper limbs, dysarthria, mild cerebellar ataxia, and central gaze nystagmus. Brain MRI showed abnormalities of the caudate nuclei and putamen similar to those of her brother. She was treated with high-dose biotin after worsening of her epilepsy, but did not show improvement until thiamine was added. Repeat MRI showed disappearance of cortical and subcortical hyperintensities. The clinical course was similar to that reported by <a href="#10" class="mim-tip-reference" title="Ozand, P. T., Gascon, G. G., Al Essa, M., Joshi, S., Al Jishi, E., Bakheet, S., Al Watban, J., Al-Kawi, M. Z., Dabbagh, O. <strong>Biotin-responsive basal ganglia disease: a novel entity.</strong> Brain 121: 1267-1279, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9679779/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9679779</a>] [<a href="https://doi.org/10.1093/brain/121.7.1267" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9679779">Ozand et al. (1998)</a>. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=9679779+20065143" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Clinical Variability</em></strong></p><p>
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<a href="#7" class="mim-tip-reference" title="Kono, S., Miyajima, H., Yoshida, K., Togawa, A., Shirakawa, K., Suzuki, H. <strong>Mutations in a thiamine-transporter gene and Wernicke's-like encephalopathy. (Letter)</strong> New. Eng. J. Med. 360: 1792-1794, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19387023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19387023</a>] [<a href="https://doi.org/10.1056/NEJMc0809100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19387023">Kono et al. (2009)</a> reported 2 Japanese brothers who presented in the second decade of life with severe complex partial seizures resulting in status epilepticus. High-dose thiamine (up to 600 mg per day) resulted in improvement of the seizures, but ophthalmoplegia, nystagmus, and ataxia continued for several weeks. Brain imaging showed high-intensity signals in the medial thalamus and periaqueductal region, similar to findings of Wernicke encephalopathy (<a href="/entry/277730">277730</a>). These changes normalized after 1 month of treatment. Subacute ophthalmoplegia with nystagmus and ataxia occurred repeatedly after discontinuation of thiamine supplementation. Serum thiamine was normal in both patients. <a href="#7" class="mim-tip-reference" title="Kono, S., Miyajima, H., Yoshida, K., Togawa, A., Shirakawa, K., Suzuki, H. <strong>Mutations in a thiamine-transporter gene and Wernicke's-like encephalopathy. (Letter)</strong> New. Eng. J. Med. 360: 1792-1794, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19387023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19387023</a>] [<a href="https://doi.org/10.1056/NEJMc0809100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19387023">Kono et al. (2009)</a> considered the disorder in these sibs to be different from BTBGD because the brain lesions did not occur in the basal ganglia. Molecular studies showed compound heterozygous mutations in the SLC19A3 gene (<a href="/entry/606152#0003">606152.0003</a>-<a href="/entry/606152#0004">606152.0004</a>). <a href="#7" class="mim-tip-reference" title="Kono, S., Miyajima, H., Yoshida, K., Togawa, A., Shirakawa, K., Suzuki, H. <strong>Mutations in a thiamine-transporter gene and Wernicke's-like encephalopathy. (Letter)</strong> New. Eng. J. Med. 360: 1792-1794, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19387023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19387023</a>] [<a href="https://doi.org/10.1056/NEJMc0809100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19387023">Kono et al. (2009)</a> suggested that a defect in the SLC19A3 gene may have induced expression of the SLC19A2 gene (<a href="/entry/603941">603941</a>), which encodes another thiamine transporter. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19387023" 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="Gerards, M., Kamps, R., van Oevelen, J., Boesten, I., Jongen, E., de Koning, B., Scholte, H. R., de Angst, I., Schoonderwoerd, K., Sefiani, A., Ratbi, I., Coppieters, W., Karim, L., de Coo, R., van den Bosch, B., Smeets, H. <strong>Exome sequencing reveals a novel Moroccan founder mutation in SLC19A3 as a new cause of early-childhood fatal Leigh syndrome.</strong> Brain 136: 882-890, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23423671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23423671</a>] [<a href="https://doi.org/10.1093/brain/awt013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23423671">Gerards et al. (2013)</a> reported 9 patients from 3 unrelated Moroccan families with a severe neurologic disorder resulting in early death. All families originated from the Al Hoceima province in northern Morocco; 2 of the families were consanguineous. Five patients from 2 families presented in early infancy with severe neurologic abnormalities consistent with encephalopathy, including inconsolable crying, axial hypotonia with hyperreflexia in the extremities, extensor plantar responses, opisthotonic posturing, roving eye movements, nystagmus, and seizures. Brain imaging showed abnormal signal intensities in the basal ganglia, thalamus, brainstem, and cerebellum, consistent with a clinical diagnosis of Leigh syndrome (<a href="/entry/256000">256000</a>). All 5 patients died of respiratory insufficiency about 1 month after birth. Two patients from the third family were described in detail. Both presented in infancy with neurologic abnormalities and were severely disabled; they died of respiratory failure at ages 20 and 15 years. There was some biochemical evidence of mitochondrial dysfunction, including decreased oxygen consumption, but respiratory chain activities were normal. The older patient showed mild transient clinical improvement with thiamine treatment. Brain imaging in both patients showed hypointense lesions in the basal ganglia and thalami, suggestive of Leigh syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23423671" 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="Kevelam, S. H., Bugiani, M., Salomons, G. S., Feigenbaum, A., Blaser, S., Prasad, C., Haberle, J., Baric, I., Bakker, I. M. C., Postma, N. L., Kanhai, W. A., Wolf, N. I., Abbink, T. E. M., Waisfisz, Q., Heutink, P., van der Knaap, M. S. <strong>Exome sequencing reveals mutated SLC19A3 in patients with an early-infantile, lethal encephalopathy.</strong> Brain 136: 1534-1543, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23482991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23482991</a>] [<a href="https://doi.org/10.1093/brain/awt054" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23482991">Kevelam et al. (2013)</a> identified a group of 7 patients from 5 unrelated families with an early-infantile lethal encephalopathy who shared an abnormal brain MRI pattern characterized by severe swelling and T2-hyperintensities in the basal ganglia, thalami, cerebral white matter, and cortex, pons, and midbrain, followed by rarefaction or cystic degeneration of the white matter, and eventually, progressive cerebral, cerebellar, and brainstem atrophy. These neurodegenerative changes occurred rapidly within a few weeks to months. Magnetic resonance spectroscopy of 5 patients showed increased lactate in the gray and white matter, and blood lactate was increased in most patients. The patients presented in the first months of life with irritability, seizures, loss of contact, developmental delay, and extensor spasms. Six patients had a preceding viral infection or vaccination before symptom onset. Six patients died of respiratory failure before age 2 years, whereas the seventh patient died at age 4 years, 8 months. Pathology of brain tissue from 2 patients demonstrated severe cerebral atrophy and microscopic brain lesions similar to Leigh syndrome. Whole-exome sequencing in 1 patient identified biallelic missense mutations in the SLC19A3 gene, and Sanger sequencing identified biallelic mutations in the subsequent 6 patients. Functional studies of the variants were not performed. <a href="#6" class="mim-tip-reference" title="Kevelam, S. H., Bugiani, M., Salomons, G. S., Feigenbaum, A., Blaser, S., Prasad, C., Haberle, J., Baric, I., Bakker, I. M. C., Postma, N. L., Kanhai, W. A., Wolf, N. I., Abbink, T. E. M., Waisfisz, Q., Heutink, P., van der Knaap, M. S. <strong>Exome sequencing reveals mutated SLC19A3 in patients with an early-infantile, lethal encephalopathy.</strong> Brain 136: 1534-1543, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23482991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23482991</a>] [<a href="https://doi.org/10.1093/brain/awt054" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23482991">Kevelam et al. (2013)</a> concluded that this severe neurodegeneration reflects the energy failure resulting from deficiency of the cofactor thiamine in the developing brain, and that this lethal phenotype expands the phenotypic spectrum associated with mutations in the SLC19A3 gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23482991" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#2" class="mim-tip-reference" title="Eichler, F. S., Swoboda, K. J., Hunt, A. L., Cestari, D. M., Rapalino, O. <strong>Case 38-2017: A 20-year-old woman with seizures and progressive dystonia.</strong> New Eng. J. Med. 377: 2376-2384, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/29236641/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">29236641</a>] [<a href="https://doi.org/10.1056/NEJMcpc1706109" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="29236641">Eichler et al. (2017)</a> reported a case record of a patient with biotin/thiamine-responsive basal ganglia disease, with a useful discussion of diagnostic considerations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=29236641" 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="Haack, T. B., Klee, D., Strom, T. M., Mayatepek, E., Meitinger, T., Prokisch, H., Distelmaier, F. <strong>Infantile Leigh-like syndrome caused by SLC19A3 mutations is a treatable disease. (Letter)</strong> Brain 137: e295, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24878502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24878502</a>] [<a href="https://doi.org/10.1093/brain/awu128" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24878502">Haack et al. (2014)</a> reported 2 brothers, born of consanguineous Turkish parents, with genetically confirmed BTBGD presenting as infantile-onset encephalopathy with features of Leigh syndrome on brain imaging. The first infant died at age 2 months. The second infant presented at age 18 days with increased blood and cerebrospinal fluid (CSF) lactate and lesions in the basal ganglia and brainstem on MRI. Empirical treatment with high doses of thiamine and biotin resulted in clinical improvement within 2 weeks: blood lactate dropped to normal, seizures remitted, and the patient showed developmental progress. Brain MRI at age 4 months showed substantial regression of the lesions, although there was some residual frontotemporal brain atrophy. Exome sequencing identified a homozygous truncating mutation in the SLC19A3 gene, consistent with a complete loss of function. <a href="#5" class="mim-tip-reference" title="Haack, T. B., Klee, D., Strom, T. M., Mayatepek, E., Meitinger, T., Prokisch, H., Distelmaier, F. <strong>Infantile Leigh-like syndrome caused by SLC19A3 mutations is a treatable disease. (Letter)</strong> Brain 137: e295, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24878502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24878502</a>] [<a href="https://doi.org/10.1093/brain/awu128" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24878502">Haack et al. (2014)</a> suggested that combined biotin/thiamine treatment is effective even in the complete absence of SLC19A3. In a response, <a href="#11" class="mim-tip-reference" title="van der Knaap, M. S., Kevelam, S. H. <strong>Reply: Infantile Leigh-like syndrome caused by SLC19A3 mutations is a treatable disease. (Letter)</strong> Brain 137: e297, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24878500/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24878500</a>] [<a href="https://doi.org/10.1093/brain/awu130" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24878500">van der Knaap and Kevelam (2014)</a> noted that the severely affected patients that they reported (<a href="#6" class="mim-tip-reference" title="Kevelam, S. H., Bugiani, M., Salomons, G. S., Feigenbaum, A., Blaser, S., Prasad, C., Haberle, J., Baric, I., Bakker, I. M. C., Postma, N. L., Kanhai, W. A., Wolf, N. I., Abbink, T. E. M., Waisfisz, Q., Heutink, P., van der Knaap, M. S. <strong>Exome sequencing reveals mutated SLC19A3 in patients with an early-infantile, lethal encephalopathy.</strong> Brain 136: 1534-1543, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23482991/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23482991</a>] [<a href="https://doi.org/10.1093/brain/awt054" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23482991">Kevelam et al., 2013</a>) were ascertained retrospectively after death, and that 2 had received biotin treatment without clinical benefit, although the neurodegeneration was already advanced. <a href="#11" class="mim-tip-reference" title="van der Knaap, M. S., Kevelam, S. H. <strong>Reply: Infantile Leigh-like syndrome caused by SLC19A3 mutations is a treatable disease. (Letter)</strong> Brain 137: e297, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24878500/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24878500</a>] [<a href="https://doi.org/10.1093/brain/awu130" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24878500">Van der Knaap and Kevelam (2014)</a> and <a href="#3" class="mim-tip-reference" title="Gerards, M., de Coo, R., Smeets, H. <strong>Reply: Infantile Leigh-like syndrome caused by SLC19A3 mutations is a treatable disease. (Letter)</strong> Brain 137: e296, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24878501/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24878501</a>] [<a href="https://doi.org/10.1093/brain/awu129" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24878501">Gerards et al. (2014)</a> commented that the patient reported by <a href="#5" class="mim-tip-reference" title="Haack, T. B., Klee, D., Strom, T. M., Mayatepek, E., Meitinger, T., Prokisch, H., Distelmaier, F. <strong>Infantile Leigh-like syndrome caused by SLC19A3 mutations is a treatable disease. (Letter)</strong> Brain 137: e295, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24878502/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24878502</a>] [<a href="https://doi.org/10.1093/brain/awu128" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24878502">Haack et al. (2014)</a> was only 4 months old, too early to determine whether the disorder is fully treatable by thiamine and biotin, but that evidence suggested benefit in some patients. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=24878502+23482991+24878500+24878501" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#8" class="mim-tip-reference" title="Ortigoza-Escobar, J. D., Serrano, M., Molero, M., Oyarzabal, A., Rebollo, M., Muchart, J., Artuch, R., Rodriguiz-Pombo, P., Perez-Duenas, B. <strong>Thiamine transporter-2 deficiency: outcome and treatment monitoring.</strong> Orphanet J. Rare Dis. 9: 92, 2014. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24957181/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24957181</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=24957181[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/10.1186/1750-1172-9-92" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="24957181">Ortigoza-Escobar et al. (2014)</a> reported clinical follow-up of 3 unrelated patients with genetically confirmed BTBGD who were treated with thiamine and biotin supplementation. The patients presented at ages 1 month, 4 years, and 15 years, respectively, with signs of encephalopathy, such as lethargy, agitation, and coma, as well as focal or generalized dystonia. Brain imaging showed lesions affecting the dorsal striatum and medial thalami. The patients received early treatment with high doses of thiamine (15-30 mg/kg/day); 1 patient also received biotin (10 mg/day). All patients subsequently were treated with biotin in addition to thiamine. All patients showed clinical improvement and remained stable with no new episodes of encephalopathy at a median follow-up of 57 months. A 25-month-old boy with onset at age 1 month developed independent gait but had residual dystonia of the upper and lower limbs and expressive language delay due to oromandibular dystonia; cognition was normal. An 8-year-old girl with onset at 4 years was asymptomatic with normal neurologic examination. A 23-year-old male with onset at age 15 had mild dysarthria and dysphagia as well as focal dystonic posturing; however, he exercised regularly and was employed. In addition to clinical improvement, all patients showed improvement in signal abnormalities on brain imaging. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24957181" 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="#9" class="mim-tip-reference" title="Owen, M. J., Niemi, A.-K., Kingsmore, S. F., and others. <strong>Rapid sequencing-based diagnosis of thiamine metabolism dysfunction syndrome. (Letter)</strong> New Eng. J. Med. 384: 2159-2162, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34077649/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34077649</a>] [<a href="https://doi.org/10.1056/NEJMc2100365" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34077649">Owen et al. (2021)</a> reported rapid sequencing-based diagnosis of THMD2 in a 5-week-old male infant, born of consanguineous parents, who presented with irritability, abnormal eye deviation, and hypodense lesions on brain imaging. Family history revealed a previous child who had developed neurologic signs and progressed rapidly to epileptic encephalopathy, resulting in death at age 11 months. Genetic diagnosis occurred within 16.5 hours after a blood sample was obtained, with the identification of a homozygous frameshift variant in the SLC19A3 gene (c.597dup). Seizures had developed in the intervening period. The infant was treated with thiamine and biotin with substantial recovery within 6 hours; he was thriving at 7 months of age. The authors emphasized the potential for improved outcome in cases like this through rapid genome sequencing in a multidisciplinary and integrated medicine delivery system. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=34077649" 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 BTBGD in the families reported by <a href="#4" class="mim-tip-reference" title="Gerards, M., Kamps, R., van Oevelen, J., Boesten, I., Jongen, E., de Koning, B., Scholte, H. R., de Angst, I., Schoonderwoerd, K., Sefiani, A., Ratbi, I., Coppieters, W., Karim, L., de Coo, R., van den Bosch, B., Smeets, H. <strong>Exome sequencing reveals a novel Moroccan founder mutation in SLC19A3 as a new cause of early-childhood fatal Leigh syndrome.</strong> Brain 136: 882-890, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23423671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23423671</a>] [<a href="https://doi.org/10.1093/brain/awt013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23423671">Gerards et al. (2013)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23423671" 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>Using linkage analysis in 4 families with BTBGD, <a href="#14" class="mim-tip-reference" title="Zeng, W.-Q., Al-Yamani, E., Acierno, J. S., Jr., Slaugenhaupt, S., Gillis, T., MacDonald, M. E., Ozand, P. T., Gusella, J. F. <strong>Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3.</strong> Am. J. Hum. Genet. 77: 16-26, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15871139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15871139</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15871139[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/431216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15871139">Zeng et al. (2005)</a> mapped the genetic defect to chromosome 2q36.3 to a minimum candidate region of approximately 2 Mb on the basis of complete homozygosity. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15871139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#14" class="mim-tip-reference" title="Zeng, W.-Q., Al-Yamani, E., Acierno, J. S., Jr., Slaugenhaupt, S., Gillis, T., MacDonald, M. E., Ozand, P. T., Gusella, J. F. <strong>Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3.</strong> Am. J. Hum. Genet. 77: 16-26, 2005.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15871139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15871139</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15871139[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1086/431216" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15871139">Zeng et al. (2005)</a> found that each family with BTBGD studied by them displayed 1 of 2 different missense mutations in the SLC19A3 gene (G23V, <a href="/entry/606152#0001">606152.0001</a>; T422A, <a href="/entry/606152#0002">606152.0002</a>), which encodes a transporter related to the reduced-folate (SLC19A1; <a href="/entry/600424">600424</a>) and thiamine (SLC19A2; <a href="/entry/603941">603941</a>) transporters. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15871139" 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 Japanese brothers with biotin-thiamine-responsive basal ganglia disease characterized by diplopia, seizures, and white matter changes in the thalamus without serum thiamine deficiency, <a href="#7" class="mim-tip-reference" title="Kono, S., Miyajima, H., Yoshida, K., Togawa, A., Shirakawa, K., Suzuki, H. <strong>Mutations in a thiamine-transporter gene and Wernicke's-like encephalopathy. (Letter)</strong> New. Eng. J. Med. 360: 1792-1794, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19387023/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19387023</a>] [<a href="https://doi.org/10.1056/NEJMc0809100" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19387023">Kono et al. (2009)</a> identified compound heterozygous mutations in the SLC19A3 gene (K44E, <a href="/entry/606152#0003">606152.0003</a>; E320Q, <a href="/entry/606152#0004">606152.0004</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19387023" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a Portuguese brother and sister with biotin-responsive basal ganglia disease, <a href="#1" class="mim-tip-reference" title="Debs, R., Depienne, C., Rastetter, A., Bellanger, A., Degos, B., Galanaud, D., Keren, B., Lyon-Caen, O., Brice, A., Sedel, F. <strong>Biotin-responsive basal ganglia disease in ethnic Europeans with novel SLC19A3 mutations.</strong> Arch. Neurol. 67: 126-130, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20065143/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20065143</a>] [<a href="https://doi.org/10.1001/archneurol.2009.293" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20065143">Debs et al. (2010)</a> identified compound heterozygosity for 2 truncating mutations in the SLC19A3 gene (<a href="/entry/606152#0005">606152.0005</a>-<a href="/entry/606152#0006">606152.0006</a>), confirming that the disorder results from loss of function of this transporter. Each unaffected parent was heterozygous for 1 of the mutations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20065143" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In affected individuals from 3 families from the Al Hoceima province in northern Morocco with BTBGD manifest as severe infantile-onset fatal encephalopathy and Leigh syndrome on brain imaging, <a href="#4" class="mim-tip-reference" title="Gerards, M., Kamps, R., van Oevelen, J., Boesten, I., Jongen, E., de Koning, B., Scholte, H. R., de Angst, I., Schoonderwoerd, K., Sefiani, A., Ratbi, I., Coppieters, W., Karim, L., de Coo, R., van den Bosch, B., Smeets, H. <strong>Exome sequencing reveals a novel Moroccan founder mutation in SLC19A3 as a new cause of early-childhood fatal Leigh syndrome.</strong> Brain 136: 882-890, 2013.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23423671/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23423671</a>] [<a href="https://doi.org/10.1093/brain/awt013" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23423671">Gerards et al. (2013)</a> identified the same homozygous truncating mutation in the SLC19A3 gene (S7X; <a href="/entry/606152#0007">606152.0007</a>). Haplotype analysis indicated a founder effect estimated to have occurred 1,250 to 1,750 years ago. The mutation in the first family was found by a combination of homozygosity mapping and whole-exome sequencing; the mutation in the subsequent 2 families was found by direct sequencing of the SLC19A3 gene in 17 patients with Leigh syndrome. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23423671" 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>Alaskan Husky encephalopathy (AHE), a fatal brain disease in young Alaskan Husky dogs, presents as a multifocal central nervous system deficit with seizures, altered mentation, dysphagia, central blindness, hypermetria, proprioceptive positioning deficits, ataxia, and tetraparesis. Brain imaging shows abnormal intracranial lesions consistent with Leigh syndrome in humans. <a href="#12" class="mim-tip-reference" title="Vernau, K. M., Runstadler, J. A., Brown, E. A., Cameron, J. M., Huson, H. J., Higgins, R. J., Ackerley, C., Sturges, B. K., Dickinson, P. J., Puschner, B., Giulivi, C., Shelton, G. D., Robinson, B. H., DiMauro, S., Bollen, A. W., Bannasch, D. L. <strong>Genome-wide association analysis identifies a mutation in the thiamine transporter 2 (SLC19A3) gene associated with Alaskan Husky encephalopathy.</strong> PLoS One 8: e57195, 2013. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23469184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23469184</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23469184[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/10.1371/journal.pone.0057195" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="23469184">Vernau et al. (2013)</a> determined that AHE is caused by a homozygous truncating mutation (c.624insTTGC, c.625C-A) in the Slc19a3.1 gene. Heterozygosity for the mutation was found in 15 of 41 healthy Alaskan Husky control dogs, but not in another 187 dogs of different breeds. Canines have 2 paralogs of SLC19A3, Slc19a3.1 and Slc19a3.2, resulting from gene duplication. Slc19a3.1 is primarily expressed in the cerebrum, cerebellum, spinal cord, kidney, and testes, whereas Slc19a3.2 is mainly expressed in the kidney and liver, suggesting tissue-specific expression of these paralogs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=23469184" 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="#13" class="mim-tip-reference" title="Vernau, K., Napoli, E., Wong, S., Ross-Inta, C., Cameron, J., Bannasch, D., Bollen, A., Dickinson, P., Giulivi, C. <strong>Thiamine deficiency-mediated brain mitochondrial pathology in Alaskan Huskies with mutation in SLC19A3.1.</strong> Brain Path. 25: 441-453, 2015.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25117056/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25117056</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25117056[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/10.1111/bpa.12188" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="25117056">Vernau et al. (2015)</a> found that the cerebral cortex and thalamus of 2 dogs with AHE were severely deficient in thiamine pyrophosphate (TPP)-dependent enzymes compared to controls. These decreases in enzymatic activity were accompanied by decreases in mitochondrial mass, mtDNA copy number, and oxidative phosphorylation, although the latter decreases did not meet the threshold for a mitochondrial respiratory chain disorder. Affected brain tissue also showed evidence of increased oxidative stress. The findings indicated that the phenotype results from a brain-specific thiamine deficiency, leading to brain mitochondrial dysfunction and increased oxidative stress. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=25117056" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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[<a href="https://doi.org/10.1093/brain/awt013" target="_blank">Full Text</a>]
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<strong>Reply: Infantile Leigh-like syndrome caused by SLC19A3 mutations is a treatable disease. (Letter)</strong>
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Brain 137: e297, 2014. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/24878500/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">24878500</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=24878500" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1093/brain/awu130" target="_blank">Full Text</a>]
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Vernau, K. M., Runstadler, J. A., Brown, E. A., Cameron, J. M., Huson, H. J., Higgins, R. J., Ackerley, C., Sturges, B. K., Dickinson, P. J., Puschner, B., Giulivi, C., Shelton, G. D., Robinson, B. H., DiMauro, S., Bollen, A. W., Bannasch, D. L.
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<strong>Genome-wide association analysis identifies a mutation in the thiamine transporter 2 (SLC19A3) gene associated with Alaskan Husky encephalopathy.</strong>
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PLoS One 8: e57195, 2013. Note: Electronic Article.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/23469184/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">23469184</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=23469184[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=23469184" 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/10.1371/journal.pone.0057195" target="_blank">Full Text</a>]
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Vernau, K., Napoli, E., Wong, S., Ross-Inta, C., Cameron, J., Bannasch, D., Bollen, A., Dickinson, P., Giulivi, C.
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<strong>Thiamine deficiency-mediated brain mitochondrial pathology in Alaskan Huskies with mutation in SLC19A3.1.</strong>
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Brain Path. 25: 441-453, 2015.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/25117056/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">25117056</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=25117056[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=25117056" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1111/bpa.12188" target="_blank">Full Text</a>]
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<a id="Zeng2005" class="mim-anchor"></a>
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Zeng, W.-Q., Al-Yamani, E., Acierno, J. S., Jr., Slaugenhaupt, S., Gillis, T., MacDonald, M. E., Ozand, P. T., Gusella, J. F.
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<strong>Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3.</strong>
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Am. J. Hum. Genet. 77: 16-26, 2005.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15871139/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15871139</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=15871139[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=15871139" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1086/431216" target="_blank">Full Text</a>]
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Cassandra L. Kniffin - updated : 06/15/2021
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Carol A. Bocchini - updated : 12/14/2017<br>Cassandra L. Kniffin - updated : 12/29/2014<br>Cassandra L. Kniffin - updated : 2/8/2012<br>Cassandra L. Kniffin - updated : 3/17/2010<br>Victor A. McKusick - updated : 6/17/2005<br>Victor A. McKusick - updated : 2/22/2005
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Victor A. McKusick : 1/15/2003
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carol : 09/27/2024
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carol : 02/22/2024<br>carol : 02/22/2024<br>carol : 06/23/2021<br>ckniffin : 06/15/2021<br>carol : 12/14/2017<br>carol : 06/08/2017<br>mcolton : 06/18/2015<br>carol : 12/30/2014<br>mcolton : 12/29/2014<br>ckniffin : 12/29/2014<br>carol : 2/10/2012<br>carol : 2/10/2012<br>ckniffin : 2/8/2012<br>wwang : 3/23/2010<br>ckniffin : 3/17/2010<br>alopez : 7/1/2008<br>terry : 6/30/2008<br>alopez : 6/17/2005<br>alopez : 6/17/2005<br>terry : 6/17/2005<br>carol : 3/8/2005<br>terry : 2/22/2005<br>ckniffin : 11/29/2004<br>carol : 1/15/2003
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<strong>#</strong> 607483
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BASAL GANGLIA DISEASE, BIOTIN-THIAMINE RESPONSIVE; BTBGD
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THIAMINE METABOLISM DYSFUNCTION SYNDROME 2 (BIOTIN- AND THIAMINE-RESPONSIVE TYPE); THMD2<br />
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BASAL GANGLIA DISEASE, BIOTIN-RESPONSIVE; BBGD<br />
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ENCEPHALOPATHY, THIAMINE-RESPONSIVE
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<strong>SNOMEDCT:</strong> 703522009;
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<strong>ORPHA:</strong> 199348, 263410, 65284;
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<strong>DO:</strong> 0050659;
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<strong>Phenotype-Gene Relationships</strong>
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2q36.3
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Thiamine metabolism dysfunction syndrome 2 (biotin/thiamine-responsive basal ganglia disease type)
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607483
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Autosomal recessive
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3
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SLC19A3
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606152
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<p>A number sign (#) is used with this entry because biotin-thiamine-responsive basal ganglia disease (BTBGD), also known as metabolism dysfunction syndrome-2 (THMD2) or thiamine-responsive encephalopathy, is caused by homozygous or compound heterozygous mutation in the SLC19A3 gene (606152), which encodes a thiamine transporter, on chromosome 2q36.</p>
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<p>Biotin-thiamine-responsive basal ganglia disease (BTBGD), also known as metabolism dysfunction syndrome-2 (THMD2) or thiamine-responsive encephalopathy, is an autosomal recessive metabolic disorder characterized by episodic encephalopathy, often triggered by febrile illness, presenting as confusion, seizures, external ophthalmoplegia, dysphagia, and sometimes coma and death. Administration of high doses of biotin, and sometimes thiamine, during these crises results in partial or complete improvement within days. If untreated, encephalopathies can result in permanent dystonia. Brain imaging may show characteristic bilateral lesions of the basal ganglia. It is not known why biotin administration results in clinical improvement, as the molecular basis of the disorder is mutation in a gene encoding a thiamine transporter. However, biotin may increase the gene expression of SLC19A3 (summary by Debs et al., 2010). </p><p>For a discussion of genetic heterogeneity of disorders due to thiamine metabolism dysfunction, see THMD1 (249270).</p>
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<p>Ozand et al. (1998) described a biotin-responsive basal ganglia disease in 10 patients, 8 of whom were Saudi, 1 Syrian, and 1 of Yemen origin. The parents in all cases were consanguineous, being first cousins in 7 of the 10. In 1 family with first-cousin parents, 2 sisters were affected and 4 of their sibs, 2 boys and 2 girls, had died of a similar disease without diagnosis. Presentation ranged from 1 to 14 years. The disease appeared at onset as a subacute encephalopathy, with confusion, dysarthria, and dysphagia and occasional supranuclear facial nerve palsy or external ophthalmoplegia, and progressed to severe cogwheel rigidity, dystonia, and quadriparesis. These symptoms disappeared within a few days if biotin (5-10 mg/kg/day) was administered, and there were no neurologic sequelae. Symptoms reappeared within 1 month if biotin was discontinued. Patients diagnosed late, or who had had repeat episodes, suffered from residual symptoms such as paraparesis, mild mental retardation, or dystonia. Biochemical studies of intermediary metabolism, autoimmune toxicologic studies, enzyme assays including those for biotinidase (609019), carboxylase, and lysosomal activities, and bacterial and viral studies were all normal. The etiology was thought to be related to a defect in the transporter of biotin across the blood-brain barrier. The only consistent radiologic abnormality was central necrosis of the head of the caudate bilaterally and complete, or partial, involvement of the putamen on brain MRI. This finding was present during the initial acute encephalopathy and remained unchanged during follow-up of 3 to 10 years. </p><p>Zeng et al. (2005) stated that all patients with biotin-responsive basal ganglia disease diagnosed to that time were of Saudi, Syrian, or Yemeni ancestry, and all had consanguineous parents. </p><p>Debs et al. (2010) reported a Portuguese brother and sister with biotin-responsive basal ganglia disease. At age 7 years, the brother developed a progressive subacute encephalopathy with confusion, inability to walk, loss of speech, swallowing dysfunction, and generalized seizures after a benign illness. He recovered, but had residual dystonia, seizures, and pyramidal signs associated with signal abnormalities of the putamen and caudate. At age 33, he again presented with subacute neurologic deterioration characterized by with confusion, severe gait ataxia, mutism, swallowing dysfunction, gaze palsy, and bilateral ptosis. Brain MRI showed diffuse signal abnormalities in cortical and subcortical areas, thalami, and mesencephalon. Treatment with high-dose biotin (600 mg/day) resulted in improvement of clinical features and disappearance of signal abnormalities on follow-up MRI. His sister developed simple partial motor seizures of the right upper limb at age 12 years. At age 20, she had subacute neurologic deterioration with generalized seizures, loss of ambulation, swallowing dysfunction, and dysarthria. She recovered but had residual dystonia of the face and upper limbs, dysarthria, mild cerebellar ataxia, and central gaze nystagmus. Brain MRI showed abnormalities of the caudate nuclei and putamen similar to those of her brother. She was treated with high-dose biotin after worsening of her epilepsy, but did not show improvement until thiamine was added. Repeat MRI showed disappearance of cortical and subcortical hyperintensities. The clinical course was similar to that reported by Ozand et al. (1998). </p><p><strong><em>Clinical Variability</em></strong></p><p>
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Kono et al. (2009) reported 2 Japanese brothers who presented in the second decade of life with severe complex partial seizures resulting in status epilepticus. High-dose thiamine (up to 600 mg per day) resulted in improvement of the seizures, but ophthalmoplegia, nystagmus, and ataxia continued for several weeks. Brain imaging showed high-intensity signals in the medial thalamus and periaqueductal region, similar to findings of Wernicke encephalopathy (277730). These changes normalized after 1 month of treatment. Subacute ophthalmoplegia with nystagmus and ataxia occurred repeatedly after discontinuation of thiamine supplementation. Serum thiamine was normal in both patients. Kono et al. (2009) considered the disorder in these sibs to be different from BTBGD because the brain lesions did not occur in the basal ganglia. Molecular studies showed compound heterozygous mutations in the SLC19A3 gene (606152.0003-606152.0004). Kono et al. (2009) suggested that a defect in the SLC19A3 gene may have induced expression of the SLC19A2 gene (603941), which encodes another thiamine transporter. </p><p>Gerards et al. (2013) reported 9 patients from 3 unrelated Moroccan families with a severe neurologic disorder resulting in early death. All families originated from the Al Hoceima province in northern Morocco; 2 of the families were consanguineous. Five patients from 2 families presented in early infancy with severe neurologic abnormalities consistent with encephalopathy, including inconsolable crying, axial hypotonia with hyperreflexia in the extremities, extensor plantar responses, opisthotonic posturing, roving eye movements, nystagmus, and seizures. Brain imaging showed abnormal signal intensities in the basal ganglia, thalamus, brainstem, and cerebellum, consistent with a clinical diagnosis of Leigh syndrome (256000). All 5 patients died of respiratory insufficiency about 1 month after birth. Two patients from the third family were described in detail. Both presented in infancy with neurologic abnormalities and were severely disabled; they died of respiratory failure at ages 20 and 15 years. There was some biochemical evidence of mitochondrial dysfunction, including decreased oxygen consumption, but respiratory chain activities were normal. The older patient showed mild transient clinical improvement with thiamine treatment. Brain imaging in both patients showed hypointense lesions in the basal ganglia and thalami, suggestive of Leigh syndrome. </p><p>Kevelam et al. (2013) identified a group of 7 patients from 5 unrelated families with an early-infantile lethal encephalopathy who shared an abnormal brain MRI pattern characterized by severe swelling and T2-hyperintensities in the basal ganglia, thalami, cerebral white matter, and cortex, pons, and midbrain, followed by rarefaction or cystic degeneration of the white matter, and eventually, progressive cerebral, cerebellar, and brainstem atrophy. These neurodegenerative changes occurred rapidly within a few weeks to months. Magnetic resonance spectroscopy of 5 patients showed increased lactate in the gray and white matter, and blood lactate was increased in most patients. The patients presented in the first months of life with irritability, seizures, loss of contact, developmental delay, and extensor spasms. Six patients had a preceding viral infection or vaccination before symptom onset. Six patients died of respiratory failure before age 2 years, whereas the seventh patient died at age 4 years, 8 months. Pathology of brain tissue from 2 patients demonstrated severe cerebral atrophy and microscopic brain lesions similar to Leigh syndrome. Whole-exome sequencing in 1 patient identified biallelic missense mutations in the SLC19A3 gene, and Sanger sequencing identified biallelic mutations in the subsequent 6 patients. Functional studies of the variants were not performed. Kevelam et al. (2013) concluded that this severe neurodegeneration reflects the energy failure resulting from deficiency of the cofactor thiamine in the developing brain, and that this lethal phenotype expands the phenotypic spectrum associated with mutations in the SLC19A3 gene. </p>
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<strong>Diagnosis</strong>
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<p>Eichler et al. (2017) reported a case record of a patient with biotin/thiamine-responsive basal ganglia disease, with a useful discussion of diagnostic considerations. </p>
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<p>Haack et al. (2014) reported 2 brothers, born of consanguineous Turkish parents, with genetically confirmed BTBGD presenting as infantile-onset encephalopathy with features of Leigh syndrome on brain imaging. The first infant died at age 2 months. The second infant presented at age 18 days with increased blood and cerebrospinal fluid (CSF) lactate and lesions in the basal ganglia and brainstem on MRI. Empirical treatment with high doses of thiamine and biotin resulted in clinical improvement within 2 weeks: blood lactate dropped to normal, seizures remitted, and the patient showed developmental progress. Brain MRI at age 4 months showed substantial regression of the lesions, although there was some residual frontotemporal brain atrophy. Exome sequencing identified a homozygous truncating mutation in the SLC19A3 gene, consistent with a complete loss of function. Haack et al. (2014) suggested that combined biotin/thiamine treatment is effective even in the complete absence of SLC19A3. In a response, van der Knaap and Kevelam (2014) noted that the severely affected patients that they reported (Kevelam et al., 2013) were ascertained retrospectively after death, and that 2 had received biotin treatment without clinical benefit, although the neurodegeneration was already advanced. Van der Knaap and Kevelam (2014) and Gerards et al. (2014) commented that the patient reported by Haack et al. (2014) was only 4 months old, too early to determine whether the disorder is fully treatable by thiamine and biotin, but that evidence suggested benefit in some patients. </p><p>Ortigoza-Escobar et al. (2014) reported clinical follow-up of 3 unrelated patients with genetically confirmed BTBGD who were treated with thiamine and biotin supplementation. The patients presented at ages 1 month, 4 years, and 15 years, respectively, with signs of encephalopathy, such as lethargy, agitation, and coma, as well as focal or generalized dystonia. Brain imaging showed lesions affecting the dorsal striatum and medial thalami. The patients received early treatment with high doses of thiamine (15-30 mg/kg/day); 1 patient also received biotin (10 mg/day). All patients subsequently were treated with biotin in addition to thiamine. All patients showed clinical improvement and remained stable with no new episodes of encephalopathy at a median follow-up of 57 months. A 25-month-old boy with onset at age 1 month developed independent gait but had residual dystonia of the upper and lower limbs and expressive language delay due to oromandibular dystonia; cognition was normal. An 8-year-old girl with onset at 4 years was asymptomatic with normal neurologic examination. A 23-year-old male with onset at age 15 had mild dysarthria and dysphagia as well as focal dystonic posturing; however, he exercised regularly and was employed. In addition to clinical improvement, all patients showed improvement in signal abnormalities on brain imaging. </p><p>Owen et al. (2021) reported rapid sequencing-based diagnosis of THMD2 in a 5-week-old male infant, born of consanguineous parents, who presented with irritability, abnormal eye deviation, and hypodense lesions on brain imaging. Family history revealed a previous child who had developed neurologic signs and progressed rapidly to epileptic encephalopathy, resulting in death at age 11 months. Genetic diagnosis occurred within 16.5 hours after a blood sample was obtained, with the identification of a homozygous frameshift variant in the SLC19A3 gene (c.597dup). Seizures had developed in the intervening period. The infant was treated with thiamine and biotin with substantial recovery within 6 hours; he was thriving at 7 months of age. The authors emphasized the potential for improved outcome in cases like this through rapid genome sequencing in a multidisciplinary and integrated medicine delivery system. </p>
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<strong>Inheritance</strong>
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<p>The transmission pattern of BTBGD in the families reported by Gerards et al. (2013) was consistent with autosomal recessive inheritance. </p>
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<strong>Mapping</strong>
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<p>Using linkage analysis in 4 families with BTBGD, Zeng et al. (2005) mapped the genetic defect to chromosome 2q36.3 to a minimum candidate region of approximately 2 Mb on the basis of complete homozygosity. </p>
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<strong>Molecular Genetics</strong>
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<p>Zeng et al. (2005) found that each family with BTBGD studied by them displayed 1 of 2 different missense mutations in the SLC19A3 gene (G23V, 606152.0001; T422A, 606152.0002), which encodes a transporter related to the reduced-folate (SLC19A1; 600424) and thiamine (SLC19A2; 603941) transporters. </p><p>In 2 Japanese brothers with biotin-thiamine-responsive basal ganglia disease characterized by diplopia, seizures, and white matter changes in the thalamus without serum thiamine deficiency, Kono et al. (2009) identified compound heterozygous mutations in the SLC19A3 gene (K44E, 606152.0003; E320Q, 606152.0004). </p><p>In a Portuguese brother and sister with biotin-responsive basal ganglia disease, Debs et al. (2010) identified compound heterozygosity for 2 truncating mutations in the SLC19A3 gene (606152.0005-606152.0006), confirming that the disorder results from loss of function of this transporter. Each unaffected parent was heterozygous for 1 of the mutations. </p>
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<strong>Population Genetics</strong>
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<p>In affected individuals from 3 families from the Al Hoceima province in northern Morocco with BTBGD manifest as severe infantile-onset fatal encephalopathy and Leigh syndrome on brain imaging, Gerards et al. (2013) identified the same homozygous truncating mutation in the SLC19A3 gene (S7X; 606152.0007). Haplotype analysis indicated a founder effect estimated to have occurred 1,250 to 1,750 years ago. The mutation in the first family was found by a combination of homozygosity mapping and whole-exome sequencing; the mutation in the subsequent 2 families was found by direct sequencing of the SLC19A3 gene in 17 patients with Leigh syndrome. </p>
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<p>Alaskan Husky encephalopathy (AHE), a fatal brain disease in young Alaskan Husky dogs, presents as a multifocal central nervous system deficit with seizures, altered mentation, dysphagia, central blindness, hypermetria, proprioceptive positioning deficits, ataxia, and tetraparesis. Brain imaging shows abnormal intracranial lesions consistent with Leigh syndrome in humans. Vernau et al. (2013) determined that AHE is caused by a homozygous truncating mutation (c.624insTTGC, c.625C-A) in the Slc19a3.1 gene. Heterozygosity for the mutation was found in 15 of 41 healthy Alaskan Husky control dogs, but not in another 187 dogs of different breeds. Canines have 2 paralogs of SLC19A3, Slc19a3.1 and Slc19a3.2, resulting from gene duplication. Slc19a3.1 is primarily expressed in the cerebrum, cerebellum, spinal cord, kidney, and testes, whereas Slc19a3.2 is mainly expressed in the kidney and liver, suggesting tissue-specific expression of these paralogs. </p><p>Vernau et al. (2015) found that the cerebral cortex and thalamus of 2 dogs with AHE were severely deficient in thiamine pyrophosphate (TPP)-dependent enzymes compared to controls. These decreases in enzymatic activity were accompanied by decreases in mitochondrial mass, mtDNA copy number, and oxidative phosphorylation, although the latter decreases did not meet the threshold for a mitochondrial respiratory chain disorder. Affected brain tissue also showed evidence of increased oxidative stress. The findings indicated that the phenotype results from a brain-specific thiamine deficiency, leading to brain mitochondrial dysfunction and increased oxidative stress. </p>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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</div>
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Debs, R., Depienne, C., Rastetter, A., Bellanger, A., Degos, B., Galanaud, D., Keren, B., Lyon-Caen, O., Brice, A., Sedel, F.
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<strong>Biotin-responsive basal ganglia disease in ethnic Europeans with novel SLC19A3 mutations.</strong>
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Arch. Neurol. 67: 126-130, 2010.
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[PubMed: 20065143]
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[Full Text: https://doi.org/10.1001/archneurol.2009.293]
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</li>
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Eichler, F. S., Swoboda, K. J., Hunt, A. L., Cestari, D. M., Rapalino, O.
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<strong>Case 38-2017: A 20-year-old woman with seizures and progressive dystonia.</strong>
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New Eng. J. Med. 377: 2376-2384, 2017.
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[PubMed: 29236641]
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[Full Text: https://doi.org/10.1056/NEJMcpc1706109]
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<li>
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<p class="mim-text-font">
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Gerards, M., de Coo, R., Smeets, H.
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<strong>Reply: Infantile Leigh-like syndrome caused by SLC19A3 mutations is a treatable disease. (Letter)</strong>
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Brain 137: e296, 2014. Note: Electronic Article.
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[PubMed: 24878501]
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[Full Text: https://doi.org/10.1093/brain/awu129]
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</li>
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<li>
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Gerards, M., Kamps, R., van Oevelen, J., Boesten, I., Jongen, E., de Koning, B., Scholte, H. R., de Angst, I., Schoonderwoerd, K., Sefiani, A., Ratbi, I., Coppieters, W., Karim, L., de Coo, R., van den Bosch, B., Smeets, H.
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<strong>Exome sequencing reveals a novel Moroccan founder mutation in SLC19A3 as a new cause of early-childhood fatal Leigh syndrome.</strong>
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Brain 136: 882-890, 2013.
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[PubMed: 23423671]
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[Full Text: https://doi.org/10.1093/brain/awt013]
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</li>
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<li>
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Haack, T. B., Klee, D., Strom, T. M., Mayatepek, E., Meitinger, T., Prokisch, H., Distelmaier, F.
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<strong>Infantile Leigh-like syndrome caused by SLC19A3 mutations is a treatable disease. (Letter)</strong>
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Brain 137: e295, 2014. Note: Electronic Article.
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[PubMed: 24878502]
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[Full Text: https://doi.org/10.1093/brain/awu128]
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<li>
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Kevelam, S. H., Bugiani, M., Salomons, G. S., Feigenbaum, A., Blaser, S., Prasad, C., Haberle, J., Baric, I., Bakker, I. M. C., Postma, N. L., Kanhai, W. A., Wolf, N. I., Abbink, T. E. M., Waisfisz, Q., Heutink, P., van der Knaap, M. S.
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<strong>Exome sequencing reveals mutated SLC19A3 in patients with an early-infantile, lethal encephalopathy.</strong>
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Brain 136: 1534-1543, 2013.
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[PubMed: 23482991]
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[Full Text: https://doi.org/10.1093/brain/awt054]
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<li>
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<p class="mim-text-font">
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Kono, S., Miyajima, H., Yoshida, K., Togawa, A., Shirakawa, K., Suzuki, H.
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<strong>Mutations in a thiamine-transporter gene and Wernicke's-like encephalopathy. (Letter)</strong>
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New. Eng. J. Med. 360: 1792-1794, 2009.
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[PubMed: 19387023]
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[Full Text: https://doi.org/10.1056/NEJMc0809100]
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<p class="mim-text-font">
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Ortigoza-Escobar, J. D., Serrano, M., Molero, M., Oyarzabal, A., Rebollo, M., Muchart, J., Artuch, R., Rodriguiz-Pombo, P., Perez-Duenas, B.
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<strong>Thiamine transporter-2 deficiency: outcome and treatment monitoring.</strong>
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Orphanet J. Rare Dis. 9: 92, 2014. Note: Electronic Article.
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[PubMed: 24957181]
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[Full Text: https://doi.org/10.1186/1750-1172-9-92]
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<p class="mim-text-font">
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Owen, M. J., Niemi, A.-K., Kingsmore, S. F., and others.
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<strong>Rapid sequencing-based diagnosis of thiamine metabolism dysfunction syndrome. (Letter)</strong>
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New Eng. J. Med. 384: 2159-2162, 2021.
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[PubMed: 34077649]
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[Full Text: https://doi.org/10.1056/NEJMc2100365]
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Ozand, P. T., Gascon, G. G., Al Essa, M., Joshi, S., Al Jishi, E., Bakheet, S., Al Watban, J., Al-Kawi, M. Z., Dabbagh, O.
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<strong>Biotin-responsive basal ganglia disease: a novel entity.</strong>
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Brain 121: 1267-1279, 1998.
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[PubMed: 9679779]
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[Full Text: https://doi.org/10.1093/brain/121.7.1267]
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</li>
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<p class="mim-text-font">
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van der Knaap, M. S., Kevelam, S. H.
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<strong>Reply: Infantile Leigh-like syndrome caused by SLC19A3 mutations is a treatable disease. (Letter)</strong>
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Brain 137: e297, 2014. Note: Electronic Article.
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[PubMed: 24878500]
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[Full Text: https://doi.org/10.1093/brain/awu130]
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<p class="mim-text-font">
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Vernau, K. M., Runstadler, J. A., Brown, E. A., Cameron, J. M., Huson, H. J., Higgins, R. J., Ackerley, C., Sturges, B. K., Dickinson, P. J., Puschner, B., Giulivi, C., Shelton, G. D., Robinson, B. H., DiMauro, S., Bollen, A. W., Bannasch, D. L.
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<strong>Genome-wide association analysis identifies a mutation in the thiamine transporter 2 (SLC19A3) gene associated with Alaskan Husky encephalopathy.</strong>
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PLoS One 8: e57195, 2013. Note: Electronic Article.
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[PubMed: 23469184]
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[Full Text: https://doi.org/10.1371/journal.pone.0057195]
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<p class="mim-text-font">
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Vernau, K., Napoli, E., Wong, S., Ross-Inta, C., Cameron, J., Bannasch, D., Bollen, A., Dickinson, P., Giulivi, C.
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<strong>Thiamine deficiency-mediated brain mitochondrial pathology in Alaskan Huskies with mutation in SLC19A3.1.</strong>
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Brain Path. 25: 441-453, 2015.
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[PubMed: 25117056]
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[Full Text: https://doi.org/10.1111/bpa.12188]
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Zeng, W.-Q., Al-Yamani, E., Acierno, J. S., Jr., Slaugenhaupt, S., Gillis, T., MacDonald, M. E., Ozand, P. T., Gusella, J. F.
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<strong>Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3.</strong>
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Am. J. Hum. Genet. 77: 16-26, 2005.
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[PubMed: 15871139]
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[Full Text: https://doi.org/10.1086/431216]
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Contributors:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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Cassandra L. Kniffin - updated : 06/15/2021<br>Carol A. Bocchini - updated : 12/14/2017<br>Cassandra L. Kniffin - updated : 12/29/2014<br>Cassandra L. Kniffin - updated : 2/8/2012<br>Cassandra L. Kniffin - updated : 3/17/2010<br>Victor A. McKusick - updated : 6/17/2005<br>Victor A. McKusick - updated : 2/22/2005
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Victor A. McKusick : 1/15/2003
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Edit History:
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carol : 09/27/2024<br>carol : 02/22/2024<br>carol : 02/22/2024<br>carol : 06/23/2021<br>ckniffin : 06/15/2021<br>carol : 12/14/2017<br>carol : 06/08/2017<br>mcolton : 06/18/2015<br>carol : 12/30/2014<br>mcolton : 12/29/2014<br>ckniffin : 12/29/2014<br>carol : 2/10/2012<br>carol : 2/10/2012<br>ckniffin : 2/8/2012<br>wwang : 3/23/2010<br>ckniffin : 3/17/2010<br>alopez : 7/1/2008<br>terry : 6/30/2008<br>alopez : 6/17/2005<br>alopez : 6/17/2005<br>terry : 6/17/2005<br>carol : 3/8/2005<br>terry : 2/22/2005<br>ckniffin : 11/29/2004<br>carol : 1/15/2003
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OMIM<sup>®</sup> and Online Mendelian Inheritance in Man<sup>®</sup> are registered trademarks of the Johns Hopkins University.
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