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<title>
Entry
- #249270 - THIAMINE-RESPONSIVE MEGALOBLASTIC ANEMIA SYNDROME; TRMA
- OMIM
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<span class="h4">#249270</span>
<br />
<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/249270"><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="#clinicalManagement">Clinical Management</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#mapping">Mapping</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#inheritance">Inheritance</a>
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<li role="presentation" style="margin-left: 1em">
<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#seeAlso"><strong>See Also</strong></a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<div><a href="https://clinicaltrials.gov/search?cond=THIAMINE-RESPONSIVE MEGALOBLASTIC ANEMIA SYNDROME" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=10643&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK1282/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://medlineplus.gov/genetics/condition/thiamine-responsive-megaloblastic-anemia-syndrome" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">&#9658;</div>
&nbsp;
<div style="display: table-cell;">Animal Models</div>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
<div class="panel-body small mim-panel-body">
<div><a href="https://www.alliancegenome.org/disease/DOID:0090117" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
<div><a href="http://www.informatics.jax.org/disease/249270" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
<div><a href="https://wormbase.org/resources/disease/DOID:0090117" class="mim-tip-hint" title="Database of the biology and genome of Caenorhabditis elegans and related nematodes." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Wormbase Disease Ontology', 'domain': 'wormbase.org'})">Wormbase Disease Ontology</a></div>
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<span>
<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
<div>
<a id="title" class="mim-anchor"></a>
<div>
<a id="number" class="mim-anchor"></a>
<div class="text-right">
<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
<strong>SNOMEDCT:</strong> 237617006<br />
<strong>ORPHA:</strong> 49827<br />
<strong>DO:</strong> 0090117<br />
">ICD+</a>
</div>
<div>
<span class="h3">
<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
<span class="text-danger"><strong>#</strong></span>
249270
</span>
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<div>
<a id="preferredTitle" class="mim-anchor"></a>
<h3>
<span class="mim-font">
THIAMINE-RESPONSIVE MEGALOBLASTIC ANEMIA SYNDROME; TRMA
</span>
</h3>
</div>
<div>
<br />
</div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<p>
<span class="mim-font">
<em>Alternative titles; symbols</em>
</span>
</p>
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<div>
<h4>
<span class="mim-font">
THIAMINE METABOLISM DYSFUNCTION SYNDROME 1 (MEGALOBLASTIC ANEMIA, DIABETES MELLITUS, AND DEAFNESS TYPE); THMD1<br />
MEGALOBLASTIC ANEMIA, THIAMINE-RESPONSIVE, WITH DIABETES MELLITUS AND SENSORINEURAL DEAFNESS<br />
ROGERS SYNDROME<br />
THIAMINE-RESPONSIVE ANEMIA SYNDROME<br />
THIAMINE-RESPONSIVE MYELODYSPLASIA
</span>
</h4>
</div>
</div>
<div>
<br />
</div>
</div>
<div>
<a id="phenotypeMap" class="mim-anchor"></a>
<h4>
<span class="mim-font">
<strong>Phenotype-Gene Relationships</strong>
</span>
</h4>
<div>
<table class="table table-bordered table-condensed table-hover small mim-table-padding">
<thead>
<tr class="active">
<th>
Location
</th>
<th>
Phenotype
</th>
<th>
Phenotype <br /> MIM number
</th>
<th>
Inheritance
</th>
<th>
Phenotype <br /> mapping key
</th>
<th>
Gene/Locus
</th>
<th>
Gene/Locus <br /> MIM number
</th>
</tr>
</thead>
<tbody>
<tr>
<td>
<span class="mim-font">
<a href="/geneMap/1/1403?start=-3&limit=10&highlight=1403">
1q24.2
</a>
</span>
</td>
<td>
<span class="mim-font">
Thiamine-responsive megaloblastic anemia syndrome
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/249270"> 249270 </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">
SLC19A2
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/603941"> 603941 </a>
</span>
</td>
</tr>
</tbody>
</table>
</div>
</div>
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<a href="/clinicalSynopsis/249270" class="btn btn-warning" role="button"> Clinical Synopsis </a>
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<a href="/phenotypicSeries/PS249270" class="btn btn-info" role="button"> Phenotypic Series </a>
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&nbsp;
<div class="btn-group">
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
PheneGene Graphics <span class="caret"></span>
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<ul class="dropdown-menu" style="width: 17em;">
<li><a href="/graph/linear/249270" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
<li><a href="/graph/radial/249270" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
</ul>
</div>
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
<div>
<p />
</div>
<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small" style="margin: 5px">
<div>
<div>
<span class="h5 mim-font">
<strong> INHERITANCE </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- 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> GROWTH </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Height </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Short stature (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422065006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422065006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237836003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237836003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/237837007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">237837007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E34.31" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E34.31</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R62.52" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R62.52</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/783.43" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">783.43</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0349588&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0349588</a>, <a href="https://bioportal.bioontology.org/search?q=C0013336&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013336</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003510" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003510</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004322" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004322</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEAD & NECK </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Ears </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Sensorineural deafness <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/60700002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">60700002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H90.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H90.5</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/389.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.10</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/389.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">389.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018784&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018784</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000407" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000407</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000407" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000407</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">
- Optic atrophy (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/76976005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">76976005</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.2</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H47.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H47.20</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/377.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.10</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/377.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">377.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0029124&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0029124</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000648" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000648</a>]</span><br /> -
Maculopathy (uncommon) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/422338006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">422338006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/312999006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">312999006</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0730362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0730362</a>, <a href="https://bioportal.bioontology.org/search?q=C0024437&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0024437</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000608" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000608</a>]</span><br /> -
Cone-rod dystrophy (uncommon) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4085590&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4085590</a>, <a href="https://bioportal.bioontology.org/search?q=C3489532&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3489532</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000548" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000548</a>]</span><br /> -
Retinal degeneration (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/95695004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">95695004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0035304&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0035304</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000546" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000546</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000546" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000546</a>]</span><br /> -
Visual loss (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/7973008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">7973008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H54.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H54.7</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/369.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">369.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3665346&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3665346</a>, <a href="https://bioportal.bioontology.org/search?q=C3665386&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3665386</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000572" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000572</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000572" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000572</a>]</span><br /> -
Nystagmus (in some patients) <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 />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> CARDIOVASCULAR </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Heart </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Congenital heart defects (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/13213009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">13213009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q24.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q24.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/746.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">746.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018798&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018798</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001627" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001627</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001627" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001627</a>]</span><br /> -
Atrial septal defect (uncommon) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253366007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253366007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/405752007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">405752007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/70142008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">70142008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.10</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018817&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018817</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001631" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001631</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001631" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001631</a>]</span><br /> -
Ventricular septal defect (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/30288003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">30288003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/253549006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">253549006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/768552007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">768552007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q21.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q21.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/745.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">745.4</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0018818&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0018818</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001629" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001629</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001629" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001629</a>]</span><br /> -
Conduction defects (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/44808001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">44808001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I45.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I45.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/426.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">426.9</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/426" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">426</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0264886&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0264886</a>]</span><br /> -
Arrhythmias (in some patients) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/698247007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">698247007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I49.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I49.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/427.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">427.9</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/427" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">427</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0003811&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0003811</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011675" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011675</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011675" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011675</a>]</span><br /> -
Cardiomyopathy (uncommon) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/85898001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">85898001</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/57809008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">57809008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I51.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I51.5</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/I42" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/I42.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I42.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/425" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">425</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0878544&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0878544</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001638" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001638</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001638" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001638</a>]</span><br />
</span>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Vascular </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Cerebrovascular accidents (uncommon) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/230690007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">230690007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I63.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I63.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038454&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038454</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001297" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001297</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001297" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001297</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>
<span class="mim-font">
- Situs inversus (uncommon) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/27317008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">27317008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/43876007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">43876007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q89.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q89.3</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/759.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">759.3</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0037221&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0037221</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003363" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003363</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0001696" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001696</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001696" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001696</a>]</span><br />
</span>
</div>
<div>
<div>
<span class="h5 mim-font">
<em> Gastrointestinal </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Gastroesophageal reflux (uncommon) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/235595009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">235595009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/722884003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">722884003</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/698065002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">698065002</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K21" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K21</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K21.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K21.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/530.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">530.81</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3813607&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3813607</a>, <a href="https://bioportal.bioontology.org/search?q=C4317146&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4317146</a>, <a href="https://bioportal.bioontology.org/search?q=C0017168&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0017168</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002020" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002020</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002020" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002020</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> GENITOURINARY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Internal Genitalia (Male) </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Cryptorchidism (uncommon) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/204878001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">204878001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q53.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q53.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/752.51" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">752.51</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0010417&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0010417</a>, <a href="https://bioportal.bioontology.org/search?q=C5441920&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5441920</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000028" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000028</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000028" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000028</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> NEUROLOGIC </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<div>
<span class="h5 mim-font">
<em> Central Nervous System </em>
</span>
</div>
<div style="margin-left: 2em;">
<span class="mim-font">
- Developmental delay (uncommon) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/248290002" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">248290002</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/224958001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">224958001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F88</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/315.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">315.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0557874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0557874</a>, <a href="https://bioportal.bioontology.org/search?q=C0424605&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424605</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001263" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001263</a>]</span><br /> -
Seizures (uncommon) <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 /> -
Stroke (uncommon) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/230690007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">230690007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I63.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I63.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0038454&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0038454</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001297" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001297</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001297" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001297</a>]</span><br /> -
Ataxia (uncommon) <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/20262006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">20262006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/39384006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">39384006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/85102008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">85102008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R27.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R27.0</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/438.84" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">438.84</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0004134&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0004134</a>, <a href="https://bioportal.bioontology.org/search?q=C1135207&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1135207</a>, <a href="https://bioportal.bioontology.org/search?q=C0007758&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0007758</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0010867" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010867</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001251" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001251</a>]</span><br />
</span>
</div>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> ENDOCRINE FEATURES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Diabetes mellitus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/73211009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">73211009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/E08-E13" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">E08-E13</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">250</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011849&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011849</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000819" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000819</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000819" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000819</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> HEMATOLOGY </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Megaloblastic anemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/53165003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">53165003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D53.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D53.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0002888&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0002888</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001889" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001889</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001889" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001889</a>]</span><br /> -
Sideroblastic anemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/41841004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">41841004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D64.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D64.3</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/285.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">285.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0002896&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0002896</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001924" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001924</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001924" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001924</a>]</span><br /> -
Thrombocytopenia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/415116008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">415116008</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/302215000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">302215000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/D69.6" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">D69.6</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/287.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">287.5</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0392386&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0392386</a>, <a href="https://bioportal.bioontology.org/search?q=C0040034&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0040034</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001873" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001873</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001873" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001873</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> LABORATORY ABNORMALITIES </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Serum thiamine is normal <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3278466&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3278466</a>]</span><br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MISCELLANEOUS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Onset in early childhood (infancy to 6 years)<br /> -
Classic triad is megaloblastic anemia, diabetes, and deafness, but some patients may not have this triad<br /> -
Variable severity of phenotype and other features may be present<br /> -
Later onset associated with milder severity has been reported<br /> -
Anemia, diabetes, and deafness often show onset at different ages<br /> -
Diabetes and anemia respond to high doses of thiamine supplementation<br />
</span>
</div>
</div>
</div>
<div>
<div>
<span class="h5 mim-font">
<strong> MOLECULAR BASIS </strong>
</span>
</div>
<div style="margin-left: 2em;">
<div>
<span class="mim-font">
- Caused by mutation in the solute carrier family 19 (thiamine transporter), member 2 gene (SLC19A2, <a href="/entry/603941#0001">603941.0001</a>)<br />
</span>
</div>
</div>
</div>
<div class="text-right">
<a href="#mimClinicalSynopsisFold" data-toggle="collapse">&#9650;&nbsp;Close</a>
</div>
</div>
</div>
<div id="mimPhenotypicSeriesFold" class="well well-sm collapse mimSingletonToggleFold">
<div class="small">
<div class="row">
<div class="col-lg-12 col-md-12 col-sm-12 col-xs-12">
<h5>
Thiamine-responsive dysfunction syndrome
- <a href="/phenotypicSeries/PS249270">PS249270</a>
- 5 Entries
</h5>
</div>
</div>
<div class="row" style="margin-left: 0.125em; margin-right: 0.125em;">
<table class="table table-bordered table-condensed table-hover mim-table-padding">
<thead>
<tr>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Location</strong>
</th>
<th class="col-lg-5 col-md-5 col-sm-5 col-xs-6 text-nowrap">
<strong>Phenotype</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Inheritance</strong>
</th>
<th class="col-lg-1 col-md-1 col-sm-1 col-xs-1 text-nowrap">
<strong>Phenotype<br />mapping key</strong>
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<strong>Phenotype<br />MIM number</strong>
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<strong>Gene/Locus</strong>
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<strong>Gene/Locus<br />MIM number</strong>
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</thead>
<tbody>
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<td>
<span class="mim-font">
<a href="/geneMap/1/1403?start=-3&limit=10&highlight=1403"> 1q24.2 </a>
</span>
</td>
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<span class="mim-font">
<a href="/entry/249270"> Thiamine-responsive megaloblastic anemia syndrome </a>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
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<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 class="mim-font">
<a href="/entry/249270"> 249270 </a>
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<span class="mim-font">
<a href="/entry/603941"> SLC19A2 </a>
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<span class="mim-font">
<a href="/entry/603941"> 603941 </a>
</span>
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<td>
<span class="mim-font">
<a href="/geneMap/2/1075?start=-3&limit=10&highlight=1075"> 2q36.3 </a>
</span>
</td>
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<span class="mim-font">
<a href="/entry/607483"> Thiamine metabolism dysfunction syndrome 2 (biotin/thiamine-responsive basal ganglia disease type) </a>
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<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
</span>
</td>
<td>
<span class="mim-font">
<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/607483"> 607483 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606152"> SLC19A3 </a>
</span>
</td>
<td>
<span class="mim-font">
<a href="/entry/606152"> 606152 </a>
</span>
</td>
</tr>
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<span class="mim-font">
<a href="/geneMap/7/784?start=-3&limit=10&highlight=784"> 7q35 </a>
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</td>
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<span class="mim-font">
<a href="/entry/614458"> Thiamine metabolism dysfunction syndrome 5 (episodic encephalopathy type) </a>
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<span class="mim-font">
<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</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>
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<span class="mim-font">
<a href="/entry/614458"> 614458 </a>
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<span class="mim-font">
<a href="/entry/606370"> TPK1 </a>
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</td>
<td>
<span class="mim-font">
<a href="/entry/606370"> 606370 </a>
</span>
</td>
</tr>
<tr>
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<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>
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</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>
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<p>A number sign (#) is used with this entry because of evidence that thiamine-responsive megaloblastic anemia syndrome (TRMA), also known as thiamine metabolism dysfunction syndrome-1 (THMD1), is caused by homozygous mutation in the SLC19A2 (<a href="/entry/603941">603941</a>) gene, which encodes a thiamine transporter protein, on chromosome 1q24.</p>
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<strong>Description</strong>
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<p>Thiamine-responsive megaloblastic anemia syndrome (TRMA) comprises megaloblastic anemia, diabetes mellitus, and sensorineural deafness. Onset is typically between infancy and adolescence, but all of the cardinal findings are often not present initially. The anemia, and sometimes the diabetes, improves with high doses of thiamine. Other more variable features include optic atrophy, congenital heart defects, short stature, and stroke (summary by <a href="#4" class="mim-tip-reference" title="Bergmann, A. K., Sahai, I., Falcone, J. F., Fleming, J., Bagg, A., Borgna-Pignati, C., Casey, R., Fabris, L, Hexner, E., Mathews, L., Ribeiro, M. L., Wierenga, K. J., Neufeld, E. J. &lt;strong&gt;Thiamine-responsive megaloblastic anemia: identification of novel compound heterozygotes and mutation update.&lt;/strong&gt; J. Pediat. 155: 888-892, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19643445/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19643445&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.jpeds.2009.06.017&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19643445">Bergmann et al., 2009</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19643445" 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>Genetic Heterogeneity of Disorders Due to Thiamine Metabolism Dysfunction</em></strong></p><p>
See also episodic encephalopathies due to defects in thiamine metabolism: biotin-responsive basal ganglia disease (THMD2; <a href="/entry/607483">607483</a>), caused by mutation in the SLC19A3 gene (<a href="/entry/606152">606152</a>) on chromosome 2q36; Amish-type microcephaly (THMD3; <a href="/entry/607196">607196</a>) and bilateral striatal necrosis and progressive polyneuropathy (THMD4; <a href="/entry/613710">613710</a>), both caused by mutation in the SLC25A19 gene (<a href="/entry/606521">606521</a>) on chromosome 17q25; and THMD5 (<a href="/entry/614458">614458</a>), caused by mutation in the TPK1 gene (<a href="/entry/606370">606370</a>) on chromosome 7q35.</p>
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<p><a href="#18" class="mim-tip-reference" title="Rogers, L. E., Porter, F. S., Sidbury, J. B., Jr. &lt;strong&gt;Thiamine-responsive megaloblastic anemia.&lt;/strong&gt; J. Pediat. 74: 494-504, 1969.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5767338/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5767338&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(69)80031-4&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="5767338">Rogers et al. (1969)</a> described an 11-year-old girl with megaloblastic anemia responsive only to thiamine. She also had diabetes mellitus, amino aciduria, and sensorineural deafness. <a href="#21" class="mim-tip-reference" title="Viana, M. B., Carvalho, R. I. &lt;strong&gt;Thiamine-responsive megaloblastic anemia, sensorineural deafness, and diabetes mellitus: a new syndrome?&lt;/strong&gt; J. Pediat. 93: 235-238, 1978.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/671156/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;671156&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(78)80503-4&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="671156">Viana and Carvalho (1978)</a> described a 6-year-old girl with congenital megaloblastic anemia that responded completely only to pharmacologic doses of thiamine. Relapse occurred twice when thiamine was discontinued. As in the case of <a href="#18" class="mim-tip-reference" title="Rogers, L. E., Porter, F. S., Sidbury, J. B., Jr. &lt;strong&gt;Thiamine-responsive megaloblastic anemia.&lt;/strong&gt; J. Pediat. 74: 494-504, 1969.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/5767338/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;5767338&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(69)80031-4&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="5767338">Rogers et al. (1969)</a>, the child also had latent diabetes mellitus and sensorineural deafness. Situs inversus viscerum totalis was also present. The parents were first cousins and were partially deaf. The syndrome was further delineated and autosomal recessive inheritance corroborated by <a href="#8" class="mim-tip-reference" title="Haworth, C., Evans, D. I. K., Mitra, J., Wickramasinghe, S. N. &lt;strong&gt;Thiamine responsive anaemia: a study of two further cases.&lt;/strong&gt; Brit. J. Haemat. 50: 549-561, 1982.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6175336/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6175336&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1111/j.1365-2141.1982.tb01955.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6175336">Haworth et al. (1982)</a>, who described affected Pakistani brother and sister. The bone marrow showed megaloblastic erythropoiesis and many ringed sideroblasts, and, by electron microscopy, iron-laden mitochondria in erythroblasts. Autosomal recessive inheritance was demonstrated by the striking pedigree published by <a href="#10" class="mim-tip-reference" title="Mandel, H., Berant, M., Hazani, A., Naveh, Y. &lt;strong&gt;Thiamine-dependent beriberi in the &#x27;thiamine-responsive anemia syndrome.&#x27;.&lt;/strong&gt; New Eng. J. Med. 311: 836-838, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6472386/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6472386&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1056/NEJM198409273111307&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6472386">Mandel et al. (1984)</a>: 2 males and 3 females in 3 related sibships, each with closely related parents, were observed. The proband was the youngest reported case. She presented at age 3 months with severe anemia, diabetes, and deafness, all of which improved with high-dose thiamine treatment. The patient also showed generalized puffiness, hoarseness, and severe cardiac and neurologic disturbances, which also dramatically responded to administration of thiamine in large doses. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=5767338+6175336+6472386+671156" 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>The abnormalities in the thiamine-responsive anemia syndrome are consistent with the picture of thiamine-deficient beriberi in childhood (<a href="#6" class="mim-tip-reference" title="Burgess, R. C. &lt;strong&gt;Infantile beriberi.&lt;/strong&gt; Fed. Proc. 17 (suppl. 2): 39-48, 1958."None>Burgess, 1958</a>). Hyperglycemia has been observed in beriberi, and diabetic glucose-tolerance curves that revert to normal with thiamine replacement are described in rats with experimental thiamine deficiency. The anemia can be megaloblastic, sideroblastic or aplastic.</p><p><a href="#1" class="mim-tip-reference" title="Abboud, M. R., Alexander, D., Najjar, S. S. &lt;strong&gt;Diabetes mellitus, thiamine-dependent megaloblastic anemia, and sensorineural deafness associated with deficient alpha-ketoglutarate dehydrogenase activity.&lt;/strong&gt; J. Pediat. 107: 537-541, 1985.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/4045602/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;4045602&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(85)80011-1&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="4045602">Abboud et al. (1985)</a> reported 3 brothers with diabetes mellitus, thiamine-responsive megaloblastic anemia, and sensorineural deafness. Two had also congenital septal defects of the heart. In 1 brother the activity of thiamine-dependent enzymes was measured, revealing low alpha-ketoglutarate dehydrogenase activity which might have been responsible for sideroblastic anemia with secondary megaloblastic changes. The anemia responded to thiamine but the diabetes did not. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4045602" 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="#5" class="mim-tip-reference" title="Borgna-Pignatti, C., Marradi, P., Pinelli, L., Monetti, N., Patrini, C. &lt;strong&gt;Thiamine-responsive anemia in DIDMOAD syndrome.&lt;/strong&gt; J. Pediat. 114: 405-410, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2537896/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2537896&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(89)80558-x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2537896">Borgna-Pignatti et al. (1989)</a> described 2 Italian children, related as first cousins, who developed megaloblastic and sideroblastic anemia, neutropenia, and borderline thrombocytopenia. These authors characterized these children as having DIDMOAD syndrome (<a href="/entry/222300">222300</a>). In both children, thiamine pyrophosphate in erythrocytes and thiamine pyrophosphokinase activity were lower than the lowest values observed in control subjects. A month after institution of treatment with thiamine, the hematologic findings had returned to normal and insulin requirements had decreased. Withdrawal of thiamine repeatedly induced relapse of the anemia and increase in insulin requirements. However, a later study by <a href="#11" class="mim-tip-reference" title="Neufeld, E. J., Mandel, H., Raz, T., Szargel, R., Yandava, C. N., Stagg, A., Faure, S., Barrett, T., Buist, N., Cohen, N. &lt;strong&gt;Localization of the gene for thiamine-responsive megaloblastic anemia syndrome, on the long arm of chromosome 1, by homozygosity mapping.&lt;/strong&gt; Am. J. Hum. Genet. 61: 1335-1341, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9399900/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9399900&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/301642&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9399900">Neufeld et al. (1997)</a> determined that the patients reported by <a href="#5" class="mim-tip-reference" title="Borgna-Pignatti, C., Marradi, P., Pinelli, L., Monetti, N., Patrini, C. &lt;strong&gt;Thiamine-responsive anemia in DIDMOAD syndrome.&lt;/strong&gt; J. Pediat. 114: 405-410, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2537896/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2537896&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/s0022-3476(89)80558-x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2537896">Borgna-Pignatti et al. (1989)</a> in fact had thiamine-responsive megaloblastic anemia syndrome, with linkage to chromosome 1q. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2537896+9399900" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#3" class="mim-tip-reference" title="Bazarbachi, A., Muakkit, S., Ayas, M., Taher, A., Salem, Z., Solh, H., Haidar, J. H. &lt;strong&gt;Thiamine-responsive myelodysplasia.&lt;/strong&gt; Brit. J. Haemat. 102: 1098-1100, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9734663/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9734663&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1046/j.1365-2141.1998.00861.x&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9734663">Bazarbachi et al. (1998)</a> found reports of 15 patients with the triad of thiamine-responsive anemia, diabetes mellitus, and deafness associated with macrocytic anemia and sometimes moderate thrombocytopenia. Bone marrow aspirates usually showed ringed sideroblasts in addition to the megaloblastic changes. They described 2 new patients who presented with diabetes, deafness, and thiamine-responsive pancytopenia. Bone marrow aspirate and biopsy were typical of trilineage myelodysplasia. The findings suggested that thiamine may have a role in the regulation of hemopoiesis at the stem cell level. They proposed the designation 'thiamine-responsive myelodysplasia' for this disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9734663" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#22" class="mim-tip-reference" title="Villa, V., Rivellese, A., Di Salle, F., Iovine, C., Poggi, V., Capaldo, B. &lt;strong&gt;Acute ischemic stroke in a young woman with the thiamine-responsive megaloblastic anemia syndrome.&lt;/strong&gt; J. Clin. Endocr. Metab. 85: 947-949, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10720020/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10720020&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1210/jcem.85.3.6419&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10720020">Villa et al. (2000)</a> reported the case of a 20-year-old girl with TRMA associated with diabetes mellitus and bilateral sensorineural deafness. Megaloblastic anemia was diagnosed at 7 months and was successfully treated with multiple vitamin preparations. Diabetes was diagnosed at age 2 years and was treated with insulin for 6 months at a dose of 0.5 IU/kg BW. The diagnosis of TRMA was clinically confirmed when bilateral sensorineural deafness was detected. Thereafter, thiamine treatment was started (50 mg/day), and insulin was discontinued because of frequent episodes of hypoglycemia. At age 17 years, because of secondary amenorrhea and echographic findings of small ovarian cysts, the patient was diagnosed as having polycystic ovary syndrome and was treated with estro-progestins (12 cycles/yr of ciproterone, ethinyl estradiol). One year later, at age 18 years, the patient developed motor seizures initially involving the left leg, then rapidly extending to the whole body, followed by unconsciousness. Brain MRI and angiography showed severely reduced blood flow in the right middle cerebral artery, with a large ischemic area in the corresponding territory, absence of flow in the distal internal carotid arteries, and slight compensatory hypertrophy of the basilar artery. X-ray digital arteriography confirmed MRI findings and showed narrowing of the left superficial femoral and popliteal arteries. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10720020" 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="Bergmann, A. K., Sahai, I., Falcone, J. F., Fleming, J., Bagg, A., Borgna-Pignati, C., Casey, R., Fabris, L, Hexner, E., Mathews, L., Ribeiro, M. L., Wierenga, K. J., Neufeld, E. J. &lt;strong&gt;Thiamine-responsive megaloblastic anemia: identification of novel compound heterozygotes and mutation update.&lt;/strong&gt; J. Pediat. 155: 888-892, 2009.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/19643445/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;19643445&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1016/j.jpeds.2009.06.017&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="19643445">Bergmann et al. (2009)</a> reported 8 patients from 7 families with genetically confirmed TRMA. The patients were of various ethnic origin, including Korean, Indian, Lebanese, Honduran, Italian, Caucasian, and Portuguese. All had megaloblastic anemia, often with ringed sideroblasts, diabetes mellitus, which was often insulin-dependent, and deafness. Onset of anemia occurred between 11 months and 11 years of age; onset of diabetes between ages 1.5 years and 11 years; and onset of deafness between ages 8 months and 6 years in 6 patients and at age 30 in 1 patient. One patient had normal hearing at age 15 years. Treatment with high-dose thiamine resulted in improvement in the anemia and, in some cases, amelioration of the diabetes phenotype. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19643445" 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 id="clinicalManagement" class="mim-anchor"></a>
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<strong>Clinical Management</strong>
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<p>The patient of <a href="#13" class="mim-tip-reference" title="Poggi, V., Longo, G., DeVizia, B., Andria, G., Rindi, G., Patrini, C., Cassandro, E. &lt;strong&gt;Thiamin-responsive megaloblastic anaemia: a disorder of thiamin transport?&lt;/strong&gt; J. Inherit. Metab. Dis. 7 (suppl. 2): 153-154, 1984.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/6090807/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;6090807&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/978-94-009-5612-4_51&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="6090807">Poggi et al. (1984)</a> no longer needed insulin after the start of thiamine treatment. <a href="#14" class="mim-tip-reference" title="Poggi, V., Rindi, G., Patrini, C., De Vizia, B., Longo, G., Andria, G. &lt;strong&gt;Studies on thiamine metabolism in thiamine-responsive megaloblastic anaemia.&lt;/strong&gt; Europ. J. Pediat. 148: 307-311, 1989.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/2540004/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;2540004&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00444120&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="2540004">Poggi et al. (1989)</a> and <a href="#16" class="mim-tip-reference" title="Rindi, G., Casirola, D., Poggi, V., De Vizia, B., Patrini, C., Laforenza, U. &lt;strong&gt;Thiamine transport by erythrocytes and ghosts in thiamine-responsive megaloblastic anaemia.&lt;/strong&gt; J. Inherit. Metab. Dis. 15: 231-242, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1326679/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1326679&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF01799637&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1326679">Rindi et al. (1992)</a> reported further studies of the proband, a 5-year-old girl at the time of diagnosis, and her affected brother. <a href="#16" class="mim-tip-reference" title="Rindi, G., Casirola, D., Poggi, V., De Vizia, B., Patrini, C., Laforenza, U. &lt;strong&gt;Thiamine transport by erythrocytes and ghosts in thiamine-responsive megaloblastic anaemia.&lt;/strong&gt; J. Inherit. Metab. Dis. 15: 231-242, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1326679/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1326679&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF01799637&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1326679">Rindi et al. (1992)</a> reported that with daily administration of a lipophilic form of thiamine with enhanced bioavailability, the girl was 'still well controlled as far as anaemia and deafness are concerned. During the last 3 years, her diabetes has required insulin therapy.' The boy was well controlled as far as anemia, deafness, and diabetes were concerned, but had developed progressive optic atrophy during the previous 2 years. <a href="#16" class="mim-tip-reference" title="Rindi, G., Casirola, D., Poggi, V., De Vizia, B., Patrini, C., Laforenza, U. &lt;strong&gt;Thiamine transport by erythrocytes and ghosts in thiamine-responsive megaloblastic anaemia.&lt;/strong&gt; J. Inherit. Metab. Dis. 15: 231-242, 1992.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/1326679/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;1326679&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF01799637&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="1326679">Rindi et al. (1992)</a> concluded that the cells from TRMA patients contain low levels of thiamine compounds, probably due to their inability to take up and retain physiologic concentrations of thiamine. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=6090807+1326679+2540004" 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 id="mapping" class="mim-anchor"></a>
<h4 href="#mimMappingFold" id="mimMappingToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<strong>Mapping</strong>
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<p>Neufeld et al. (<a href="#11" class="mim-tip-reference" title="Neufeld, E. J., Mandel, H., Raz, T., Szargel, R., Yandava, C. N., Stagg, A., Faure, S., Barrett, T., Buist, N., Cohen, N. &lt;strong&gt;Localization of the gene for thiamine-responsive megaloblastic anemia syndrome, on the long arm of chromosome 1, by homozygosity mapping.&lt;/strong&gt; Am. J. Hum. Genet. 61: 1335-1341, 1997.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9399900/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9399900&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1086/301642&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9399900">1997</a>, <a href="#12" class="mim-tip-reference" title="Neufeld, E. J., Mandel, H., Raz, T., Yandava, C. N., Szargel, R., Stagg, A., Faure, S., Barrett, T. G., Cohen, N. &lt;strong&gt;Localization of the gene for the syndrome of thiamine-responsive megaloblastic anemia with diabetes and deafness to chromosome 1q23 by homozygosity mapping. (Abstract)&lt;/strong&gt; Am. J. Hum. Genet. 61 (suppl.): A14 only, 1997."None>1997</a>) performed homozygosity mapping and linkage mapping in 4 large kindreds of native Alaskan and Italian origin with TRMA. Strong evidence for linkage was found to a single marker on 1q23.2-q23.3; maximum lod = 3.7 for D1S1679. Sixteen markers spanning the region were examined in the Alaskan kindred, plus 2 additional consanguineous kindreds of Arab-Israeli origin. These results confirmed the putative disease gene interval, suggesting genetic homogeneity. Linkage analysis generated the highest combined lod score, 8.1 at theta = 0.0, with marker D1S2779. The Italian and Alaskan patients shared no haplotypes with each other nor with the Arab-Israeli families, suggesting that the disease arose independently on 3 different genetic backgrounds. Several heterozygous parents had diabetes mellitus, deafness, or megaloblastic anemia, raising the possibility that mutations at this locus predispose carriers to these manifestations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9399900" 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>Based on genetic recombination, homozygosity mapping, and linkage disequilibrium (highest lod score of 12.5 at D1S2799, at a recombination fraction of 0), <a href="#15" class="mim-tip-reference" title="Raz, T., Barrett, T., Szargel, R., Mandel, H., Neufeld, E. J., Nosaka, K., Viana, M. B., Cohen, N. &lt;strong&gt;Refined mapping of the gene for thiamine-responsive megaloblastic anemia syndrome and evidence for genetic homogeneity.&lt;/strong&gt; Hum. Genet. 103: 455-461, 1998.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/9856490/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;9856490&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/s004390050850&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="9856490">Raz et al. (1998)</a> further narrowed the TRMA interval to 4 cM. They analyzed an additional 7 families of diverse ethnic origin and confirmed homogeneity of the disease. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9856490" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Banikazemi, M., Diaz, G. A., Voussough, P., Jalali, M., Desnick, R. J., Gelb, B. D. &lt;strong&gt;Localization of the thiamine-responsive megaloblastic anemia syndrome locus to a 1.4-cM region of 1q23.&lt;/strong&gt; Molec. Genet. Metab. 66: 193-198, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10066388/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10066388&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1006/mgme.1998.2799&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10066388">Banikazemi et al. (1999)</a> narrowed the location of the TRMA locus to a 1.4-cM interval on 1q23.3. Using a P1-derived artificial chromosome (PAC) contig spanning the TRMA candidate region, <a href="#9" class="mim-tip-reference" title="Labay, V., Raz, T., Baron, D., Mandel, H., Williams, H., Barrett, T., Szargel, R., McDonald, L., Shalata, A., Nosaka, K., Gregory, S., Cohen, N. &lt;strong&gt;Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness.&lt;/strong&gt; Nature Genet. 22: 300-304, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10391221/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10391221&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/10372&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10391221">Labay et al. (1999)</a> clarified the order of genetic markers across the TRMA locus, provided 9 new polymorphic markers, and narrowed the locus to an approximately 400-kb region. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10391221+10066388" 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 id="inheritance" class="mim-anchor"></a>
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<p>The transmission pattern of TRMA in the families reported by <a href="#9" class="mim-tip-reference" title="Labay, V., Raz, T., Baron, D., Mandel, H., Williams, H., Barrett, T., Szargel, R., McDonald, L., Shalata, A., Nosaka, K., Gregory, S., Cohen, N. &lt;strong&gt;Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness.&lt;/strong&gt; Nature Genet. 22: 300-304, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10391221/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10391221&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/10372&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10391221">Labay et al. (1999)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10391221" 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 id="molecularGenetics" class="mim-anchor"></a>
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<strong>Molecular Genetics</strong>
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<p>By positional cloning, <a href="#9" class="mim-tip-reference" title="Labay, V., Raz, T., Baron, D., Mandel, H., Williams, H., Barrett, T., Szargel, R., McDonald, L., Shalata, A., Nosaka, K., Gregory, S., Cohen, N. &lt;strong&gt;Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness.&lt;/strong&gt; Nature Genet. 22: 300-304, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10391221/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10391221&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/10372&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10391221">Labay et al. (1999)</a> identified the SLC19A2 gene, which they called THTR1, within the critical TRMA locus region. In all affected members of 6 families segregating TRMA, they identified homozygous mutations in the SLC19A2 gene, which encodes a putative transmembrane protein homologous to the reduced folate carrier proteins. <a href="#9" class="mim-tip-reference" title="Labay, V., Raz, T., Baron, D., Mandel, H., Williams, H., Barrett, T., Szargel, R., McDonald, L., Shalata, A., Nosaka, K., Gregory, S., Cohen, N. &lt;strong&gt;Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness.&lt;/strong&gt; Nature Genet. 22: 300-304, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10391221/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10391221&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1038/10372&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10391221">Labay et al. (1999)</a> suggested that a defective thiamine transporter protein underlies the TRMA syndrome. They noted that studies by <a href="#17" class="mim-tip-reference" title="Rindi, G., Patrini, C., Laforenza, U., Mandel, H., Berant, M., Viana, M. B., Poggi, V., Zarra, A. N. &lt;strong&gt;Further studies on erythrocyte thiamin transport and phosphorylation in seven patients with thiamin-responsive megaloblastic anaemia.&lt;/strong&gt; J. Inherit. Metab. Dis. 17: 667-677, 1994.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/7707690/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;7707690&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1007/BF00712009&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="7707690">Rindi et al. (1994)</a> and by <a href="#20" class="mim-tip-reference" title="Stagg, A. R., Fleming, J. C., Baker, M. A., Sakamoto, M., Cohen, N., Neufeld, E. J. &lt;strong&gt;Defective high-affinity thiamine transporter leads to cell death in thiamine-responsive megaloblastic anemia syndrome fibroblasts.&lt;/strong&gt; J. Clin. Invest. 103: 723-729, 1999.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10074490/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10074490&lt;/a&gt;, &lt;a href=&quot;https://www.ncbi.nlm.nih.gov/pmc/?term=10074490[PMID]&amp;report=imagesdocsum&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed Image&#x27;, &#x27;domain&#x27;: &#x27;ncbi.nlm.nih.gov&#x27;})&quot;&gt;images&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1172/JCI3895&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10074490">Stagg et al. (1999)</a> had suggested that deficiency in a high-affinity thiamine transporter may cause this disorder. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10391221+7707690+10074490" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#19" class="mim-tip-reference" title="Scharfe, C., Hauschild, M., Klopstock, T., Janssen, A. J. M., Heidemann, P. H., Meitinger, T., Jaksch, M. &lt;strong&gt;A novel mutation in the thiamine responsive megaloblastic anaemia gene SLC19A2 in a patient with deficiency of respiratory chain complex I.&lt;/strong&gt; J. Med. Genet. 37: 669-673, 2000.[PubMed: &lt;a href=&quot;https://pubmed.ncbi.nlm.nih.gov/10978358/&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;name&#x27;: &#x27;PubMed&#x27;, &#x27;domain&#x27;: &#x27;pubmed.ncbi.nlm.nih.gov&#x27;})&quot;&gt;10978358&lt;/a&gt;] [&lt;a href=&quot;https://doi.org/10.1136/jmg.37.9.669&quot; target=&quot;_blank&quot; onclick=&quot;gtag(&#x27;event&#x27;, &#x27;mim_outbound&#x27;, {&#x27;destination&#x27;: &#x27;Publisher&#x27;})&quot;&gt;Full Text&lt;/a&gt;]" pmid="10978358">Scharfe et al. (2000)</a> reported a girl with a trp358-to-ter mutation (<a href="/entry/603941#0009">603941.0009</a>) in the SLC19A2 gene. In addition to TRMA, the girl had short stature, hepatosplenomegaly, retinal degeneration, and a brain MRI lesion. Biochemical analyses of muscle and skin biopsies revealed a severe deficiency of pyruvate dehydrogenase and complex I of the respiratory chain. These biochemical abnormalities responded to thiamine supplementation. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10978358" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<strong>See Also:</strong>
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<a href="#Duran1985" class="mim-tip-reference" title="Duran, M., Wadman, S. K. &lt;strong&gt;Thiamine-responsive inborn errors of metabolism.&lt;/strong&gt; J. Inherit. Metab. Dis. 8 (suppl. 1): 70-75, 1985.">Duran and Wadman (1985)</a>
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<a id="references"class="mim-anchor"></a>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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<a id="1" class="mim-anchor"></a>
<a id="Abboud1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Abboud, M. R., Alexander, D., Najjar, S. S.
<strong>Diabetes mellitus, thiamine-dependent megaloblastic anemia, and sensorineural deafness associated with deficient alpha-ketoglutarate dehydrogenase activity.</strong>
J. Pediat. 107: 537-541, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/4045602/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">4045602</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=4045602" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0022-3476(85)80011-1" target="_blank">Full Text</a>]
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<a id="2" class="mim-anchor"></a>
<a id="Banikazemi1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Banikazemi, M., Diaz, G. A., Voussough, P., Jalali, M., Desnick, R. J., Gelb, B. D.
<strong>Localization of the thiamine-responsive megaloblastic anemia syndrome locus to a 1.4-cM region of 1q23.</strong>
Molec. Genet. Metab. 66: 193-198, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10066388/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10066388</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10066388" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1006/mgme.1998.2799" target="_blank">Full Text</a>]
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<a id="3" class="mim-anchor"></a>
<a id="Bazarbachi1998" class="mim-anchor"></a>
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<p class="mim-text-font">
Bazarbachi, A., Muakkit, S., Ayas, M., Taher, A., Salem, Z., Solh, H., Haidar, J. H.
<strong>Thiamine-responsive myelodysplasia.</strong>
Brit. J. Haemat. 102: 1098-1100, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9734663/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9734663</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9734663" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1046/j.1365-2141.1998.00861.x" target="_blank">Full Text</a>]
</p>
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<a id="4" class="mim-anchor"></a>
<a id="Bergmann2009" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Bergmann, A. K., Sahai, I., Falcone, J. F., Fleming, J., Bagg, A., Borgna-Pignati, C., Casey, R., Fabris, L, Hexner, E., Mathews, L., Ribeiro, M. L., Wierenga, K. J., Neufeld, E. J.
<strong>Thiamine-responsive megaloblastic anemia: identification of novel compound heterozygotes and mutation update.</strong>
J. Pediat. 155: 888-892, 2009.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19643445/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19643445</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19643445" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/j.jpeds.2009.06.017" target="_blank">Full Text</a>]
</p>
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</li>
<li>
<a id="5" class="mim-anchor"></a>
<a id="Borgna-Pignatti1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Borgna-Pignatti, C., Marradi, P., Pinelli, L., Monetti, N., Patrini, C.
<strong>Thiamine-responsive anemia in DIDMOAD syndrome.</strong>
J. Pediat. 114: 405-410, 1989.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2537896/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2537896</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2537896" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0022-3476(89)80558-x" target="_blank">Full Text</a>]
</p>
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<li>
<a id="6" class="mim-anchor"></a>
<a id="Burgess1958" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Burgess, R. C.
<strong>Infantile beriberi.</strong>
Fed. Proc. 17 (suppl. 2): 39-48, 1958.
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<li>
<a id="7" class="mim-anchor"></a>
<a id="Duran1985" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Duran, M., Wadman, S. K.
<strong>Thiamine-responsive inborn errors of metabolism.</strong>
J. Inherit. Metab. Dis. 8 (suppl. 1): 70-75, 1985.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3930844/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3930844</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=3930844" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF01800663" target="_blank">Full Text</a>]
</p>
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<a id="8" class="mim-anchor"></a>
<a id="Haworth1982" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Haworth, C., Evans, D. I. K., Mitra, J., Wickramasinghe, S. N.
<strong>Thiamine responsive anaemia: a study of two further cases.</strong>
Brit. J. Haemat. 50: 549-561, 1982.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6175336/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6175336</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6175336" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1111/j.1365-2141.1982.tb01955.x" target="_blank">Full Text</a>]
</p>
</div>
</li>
<li>
<a id="9" class="mim-anchor"></a>
<a id="Labay1999" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Labay, V., Raz, T., Baron, D., Mandel, H., Williams, H., Barrett, T., Szargel, R., McDonald, L., Shalata, A., Nosaka, K., Gregory, S., Cohen, N.
<strong>Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness.</strong>
Nature Genet. 22: 300-304, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10391221/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10391221</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10391221" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1038/10372" target="_blank">Full Text</a>]
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<a id="10" class="mim-anchor"></a>
<a id="Mandel1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Mandel, H., Berant, M., Hazani, A., Naveh, Y.
<strong>Thiamine-dependent beriberi in the 'thiamine-responsive anemia syndrome.'.</strong>
New Eng. J. Med. 311: 836-838, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6472386/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6472386</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6472386" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1056/NEJM198409273111307" target="_blank">Full Text</a>]
</p>
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<a id="11" class="mim-anchor"></a>
<a id="Neufeld1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Neufeld, E. J., Mandel, H., Raz, T., Szargel, R., Yandava, C. N., Stagg, A., Faure, S., Barrett, T., Buist, N., Cohen, N.
<strong>Localization of the gene for thiamine-responsive megaloblastic anemia syndrome, on the long arm of chromosome 1, by homozygosity mapping.</strong>
Am. J. Hum. Genet. 61: 1335-1341, 1997.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9399900/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9399900</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9399900" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1086/301642" target="_blank">Full Text</a>]
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<a id="12" class="mim-anchor"></a>
<a id="Neufeld1997" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Neufeld, E. J., Mandel, H., Raz, T., Yandava, C. N., Szargel, R., Stagg, A., Faure, S., Barrett, T. G., Cohen, N.
<strong>Localization of the gene for the syndrome of thiamine-responsive megaloblastic anemia with diabetes and deafness to chromosome 1q23 by homozygosity mapping. (Abstract)</strong>
Am. J. Hum. Genet. 61 (suppl.): A14 only, 1997.
</p>
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<a id="13" class="mim-anchor"></a>
<a id="Poggi1984" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Poggi, V., Longo, G., DeVizia, B., Andria, G., Rindi, G., Patrini, C., Cassandro, E.
<strong>Thiamin-responsive megaloblastic anaemia: a disorder of thiamin transport?</strong>
J. Inherit. Metab. Dis. 7 (suppl. 2): 153-154, 1984.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/6090807/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">6090807</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=6090807" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/978-94-009-5612-4_51" target="_blank">Full Text</a>]
</p>
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<a id="14" class="mim-anchor"></a>
<a id="Poggi1989" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Poggi, V., Rindi, G., Patrini, C., De Vizia, B., Longo, G., Andria, G.
<strong>Studies on thiamine metabolism in thiamine-responsive megaloblastic anaemia.</strong>
Europ. J. Pediat. 148: 307-311, 1989.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2540004/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2540004</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2540004" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF00444120" target="_blank">Full Text</a>]
</p>
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<a id="15" class="mim-anchor"></a>
<a id="Raz1998" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Raz, T., Barrett, T., Szargel, R., Mandel, H., Neufeld, E. J., Nosaka, K., Viana, M. B., Cohen, N.
<strong>Refined mapping of the gene for thiamine-responsive megaloblastic anemia syndrome and evidence for genetic homogeneity.</strong>
Hum. Genet. 103: 455-461, 1998.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9856490/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9856490</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9856490" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/s004390050850" target="_blank">Full Text</a>]
</p>
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<a id="Rindi1992" class="mim-anchor"></a>
<div class="">
<p class="mim-text-font">
Rindi, G., Casirola, D., Poggi, V., De Vizia, B., Patrini, C., Laforenza, U.
<strong>Thiamine transport by erythrocytes and ghosts in thiamine-responsive megaloblastic anaemia.</strong>
J. Inherit. Metab. Dis. 15: 231-242, 1992.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1326679/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1326679</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1326679" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF01799637" target="_blank">Full Text</a>]
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Rindi, G., Patrini, C., Laforenza, U., Mandel, H., Berant, M., Viana, M. B., Poggi, V., Zarra, A. N.
<strong>Further studies on erythrocyte thiamin transport and phosphorylation in seven patients with thiamin-responsive megaloblastic anaemia.</strong>
J. Inherit. Metab. Dis. 17: 667-677, 1994.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7707690/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7707690</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7707690" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1007/BF00712009" target="_blank">Full Text</a>]
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<a id="Rogers1969" class="mim-anchor"></a>
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Rogers, L. E., Porter, F. S., Sidbury, J. B., Jr.
<strong>Thiamine-responsive megaloblastic anemia.</strong>
J. Pediat. 74: 494-504, 1969.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/5767338/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">5767338</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=5767338" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0022-3476(69)80031-4" target="_blank">Full Text</a>]
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<a id="Scharfe2000" class="mim-anchor"></a>
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Scharfe, C., Hauschild, M., Klopstock, T., Janssen, A. J. M., Heidemann, P. H., Meitinger, T., Jaksch, M.
<strong>A novel mutation in the thiamine responsive megaloblastic anaemia gene SLC19A2 in a patient with deficiency of respiratory chain complex I.</strong>
J. Med. Genet. 37: 669-673, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10978358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10978358</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10978358" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1136/jmg.37.9.669" target="_blank">Full Text</a>]
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<a id="Stagg1999" class="mim-anchor"></a>
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Stagg, A. R., Fleming, J. C., Baker, M. A., Sakamoto, M., Cohen, N., Neufeld, E. J.
<strong>Defective high-affinity thiamine transporter leads to cell death in thiamine-responsive megaloblastic anemia syndrome fibroblasts.</strong>
J. Clin. Invest. 103: 723-729, 1999.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10074490/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10074490</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=10074490[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=10074490" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1172/JCI3895" target="_blank">Full Text</a>]
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<a id="Viana1978" class="mim-anchor"></a>
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Viana, M. B., Carvalho, R. I.
<strong>Thiamine-responsive megaloblastic anemia, sensorineural deafness, and diabetes mellitus: a new syndrome?</strong>
J. Pediat. 93: 235-238, 1978.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/671156/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">671156</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=671156" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1016/s0022-3476(78)80503-4" target="_blank">Full Text</a>]
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<a id="Villa2000" class="mim-anchor"></a>
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Villa, V., Rivellese, A., Di Salle, F., Iovine, C., Poggi, V., Capaldo, B.
<strong>Acute ischemic stroke in a young woman with the thiamine-responsive megaloblastic anemia syndrome.</strong>
J. Clin. Endocr. Metab. 85: 947-949, 2000.
[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10720020/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10720020</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10720020" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
[<a href="https://doi.org/10.1210/jcem.85.3.6419" target="_blank">Full Text</a>]
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Cassandra L. Kniffin - updated : 2/8/2012
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Michael J. Wright - updated : 8/9/2001<br>John A. Phillips, III - updated : 2/27/2001<br>Victor A. McKusick - updated : 6/24/1999<br>Ada Hamosh - updated : 3/10/1999<br>Victor A. McKusick - updated : 2/19/1999<br>Victor A. McKusick - updated : 2/16/1998<br>Victor A. McKusick - updated : 10/22/1997
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Victor A. McKusick : 6/4/1986
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carol : 12/09/2022
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carol : 08/03/2020<br>carol : 06/08/2017<br>carol : 12/30/2014<br>carol : 2/10/2012<br>ckniffin : 2/8/2012<br>terry : 4/20/2005<br>cwells : 8/16/2001<br>cwells : 8/14/2001<br>terry : 8/9/2001<br>alopez : 2/27/2001<br>alopez : 6/29/1999<br>terry : 6/24/1999<br>carol : 4/21/1999<br>alopez : 3/11/1999<br>alopez : 3/10/1999<br>carol : 2/22/1999<br>terry : 2/19/1999<br>mark : 2/25/1998<br>terry : 2/16/1998<br>terry : 10/28/1997<br>mark : 10/27/1997<br>terry : 10/22/1997<br>terry : 5/7/1994<br>mimadm : 2/19/1994<br>carol : 7/13/1992<br>carol : 7/8/1992<br>supermim : 3/17/1992<br>supermim : 3/20/1990
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<strong>#</strong> 249270
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THIAMINE-RESPONSIVE MEGALOBLASTIC ANEMIA SYNDROME; TRMA
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<em>Alternative titles; symbols</em>
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THIAMINE METABOLISM DYSFUNCTION SYNDROME 1 (MEGALOBLASTIC ANEMIA, DIABETES MELLITUS, AND DEAFNESS TYPE); THMD1<br />
MEGALOBLASTIC ANEMIA, THIAMINE-RESPONSIVE, WITH DIABETES MELLITUS AND SENSORINEURAL DEAFNESS<br />
ROGERS SYNDROME<br />
THIAMINE-RESPONSIVE ANEMIA SYNDROME<br />
THIAMINE-RESPONSIVE MYELODYSPLASIA
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<strong>SNOMEDCT:</strong> 237617006; &nbsp;
<strong>ORPHA:</strong> 49827; &nbsp;
<strong>DO:</strong> 0090117; &nbsp;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus
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Gene/Locus <br /> MIM number
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1q24.2
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Thiamine-responsive megaloblastic anemia syndrome
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249270
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Autosomal recessive
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3
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SLC19A2
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603941
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that thiamine-responsive megaloblastic anemia syndrome (TRMA), also known as thiamine metabolism dysfunction syndrome-1 (THMD1), is caused by homozygous mutation in the SLC19A2 (603941) gene, which encodes a thiamine transporter protein, on chromosome 1q24.</p>
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<strong>Description</strong>
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<p>Thiamine-responsive megaloblastic anemia syndrome (TRMA) comprises megaloblastic anemia, diabetes mellitus, and sensorineural deafness. Onset is typically between infancy and adolescence, but all of the cardinal findings are often not present initially. The anemia, and sometimes the diabetes, improves with high doses of thiamine. Other more variable features include optic atrophy, congenital heart defects, short stature, and stroke (summary by Bergmann et al., 2009). </p><p><strong><em>Genetic Heterogeneity of Disorders Due to Thiamine Metabolism Dysfunction</em></strong></p><p>
See also episodic encephalopathies due to defects in thiamine metabolism: biotin-responsive basal ganglia disease (THMD2; 607483), caused by mutation in the SLC19A3 gene (606152) on chromosome 2q36; Amish-type microcephaly (THMD3; 607196) and bilateral striatal necrosis and progressive polyneuropathy (THMD4; 613710), both caused by mutation in the SLC25A19 gene (606521) on chromosome 17q25; and THMD5 (614458), caused by mutation in the TPK1 gene (606370) on chromosome 7q35.</p>
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<strong>Clinical Features</strong>
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<p>Rogers et al. (1969) described an 11-year-old girl with megaloblastic anemia responsive only to thiamine. She also had diabetes mellitus, amino aciduria, and sensorineural deafness. Viana and Carvalho (1978) described a 6-year-old girl with congenital megaloblastic anemia that responded completely only to pharmacologic doses of thiamine. Relapse occurred twice when thiamine was discontinued. As in the case of Rogers et al. (1969), the child also had latent diabetes mellitus and sensorineural deafness. Situs inversus viscerum totalis was also present. The parents were first cousins and were partially deaf. The syndrome was further delineated and autosomal recessive inheritance corroborated by Haworth et al. (1982), who described affected Pakistani brother and sister. The bone marrow showed megaloblastic erythropoiesis and many ringed sideroblasts, and, by electron microscopy, iron-laden mitochondria in erythroblasts. Autosomal recessive inheritance was demonstrated by the striking pedigree published by Mandel et al. (1984): 2 males and 3 females in 3 related sibships, each with closely related parents, were observed. The proband was the youngest reported case. She presented at age 3 months with severe anemia, diabetes, and deafness, all of which improved with high-dose thiamine treatment. The patient also showed generalized puffiness, hoarseness, and severe cardiac and neurologic disturbances, which also dramatically responded to administration of thiamine in large doses. </p><p>The abnormalities in the thiamine-responsive anemia syndrome are consistent with the picture of thiamine-deficient beriberi in childhood (Burgess, 1958). Hyperglycemia has been observed in beriberi, and diabetic glucose-tolerance curves that revert to normal with thiamine replacement are described in rats with experimental thiamine deficiency. The anemia can be megaloblastic, sideroblastic or aplastic.</p><p>Abboud et al. (1985) reported 3 brothers with diabetes mellitus, thiamine-responsive megaloblastic anemia, and sensorineural deafness. Two had also congenital septal defects of the heart. In 1 brother the activity of thiamine-dependent enzymes was measured, revealing low alpha-ketoglutarate dehydrogenase activity which might have been responsible for sideroblastic anemia with secondary megaloblastic changes. The anemia responded to thiamine but the diabetes did not. </p><p>Borgna-Pignatti et al. (1989) described 2 Italian children, related as first cousins, who developed megaloblastic and sideroblastic anemia, neutropenia, and borderline thrombocytopenia. These authors characterized these children as having DIDMOAD syndrome (222300). In both children, thiamine pyrophosphate in erythrocytes and thiamine pyrophosphokinase activity were lower than the lowest values observed in control subjects. A month after institution of treatment with thiamine, the hematologic findings had returned to normal and insulin requirements had decreased. Withdrawal of thiamine repeatedly induced relapse of the anemia and increase in insulin requirements. However, a later study by Neufeld et al. (1997) determined that the patients reported by Borgna-Pignatti et al. (1989) in fact had thiamine-responsive megaloblastic anemia syndrome, with linkage to chromosome 1q. </p><p>Bazarbachi et al. (1998) found reports of 15 patients with the triad of thiamine-responsive anemia, diabetes mellitus, and deafness associated with macrocytic anemia and sometimes moderate thrombocytopenia. Bone marrow aspirates usually showed ringed sideroblasts in addition to the megaloblastic changes. They described 2 new patients who presented with diabetes, deafness, and thiamine-responsive pancytopenia. Bone marrow aspirate and biopsy were typical of trilineage myelodysplasia. The findings suggested that thiamine may have a role in the regulation of hemopoiesis at the stem cell level. They proposed the designation 'thiamine-responsive myelodysplasia' for this disorder. </p><p>Villa et al. (2000) reported the case of a 20-year-old girl with TRMA associated with diabetes mellitus and bilateral sensorineural deafness. Megaloblastic anemia was diagnosed at 7 months and was successfully treated with multiple vitamin preparations. Diabetes was diagnosed at age 2 years and was treated with insulin for 6 months at a dose of 0.5 IU/kg BW. The diagnosis of TRMA was clinically confirmed when bilateral sensorineural deafness was detected. Thereafter, thiamine treatment was started (50 mg/day), and insulin was discontinued because of frequent episodes of hypoglycemia. At age 17 years, because of secondary amenorrhea and echographic findings of small ovarian cysts, the patient was diagnosed as having polycystic ovary syndrome and was treated with estro-progestins (12 cycles/yr of ciproterone, ethinyl estradiol). One year later, at age 18 years, the patient developed motor seizures initially involving the left leg, then rapidly extending to the whole body, followed by unconsciousness. Brain MRI and angiography showed severely reduced blood flow in the right middle cerebral artery, with a large ischemic area in the corresponding territory, absence of flow in the distal internal carotid arteries, and slight compensatory hypertrophy of the basilar artery. X-ray digital arteriography confirmed MRI findings and showed narrowing of the left superficial femoral and popliteal arteries. </p><p>Bergmann et al. (2009) reported 8 patients from 7 families with genetically confirmed TRMA. The patients were of various ethnic origin, including Korean, Indian, Lebanese, Honduran, Italian, Caucasian, and Portuguese. All had megaloblastic anemia, often with ringed sideroblasts, diabetes mellitus, which was often insulin-dependent, and deafness. Onset of anemia occurred between 11 months and 11 years of age; onset of diabetes between ages 1.5 years and 11 years; and onset of deafness between ages 8 months and 6 years in 6 patients and at age 30 in 1 patient. One patient had normal hearing at age 15 years. Treatment with high-dose thiamine resulted in improvement in the anemia and, in some cases, amelioration of the diabetes phenotype. </p>
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<strong>Clinical Management</strong>
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<p>The patient of Poggi et al. (1984) no longer needed insulin after the start of thiamine treatment. Poggi et al. (1989) and Rindi et al. (1992) reported further studies of the proband, a 5-year-old girl at the time of diagnosis, and her affected brother. Rindi et al. (1992) reported that with daily administration of a lipophilic form of thiamine with enhanced bioavailability, the girl was 'still well controlled as far as anaemia and deafness are concerned. During the last 3 years, her diabetes has required insulin therapy.' The boy was well controlled as far as anemia, deafness, and diabetes were concerned, but had developed progressive optic atrophy during the previous 2 years. Rindi et al. (1992) concluded that the cells from TRMA patients contain low levels of thiamine compounds, probably due to their inability to take up and retain physiologic concentrations of thiamine. </p>
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<strong>Mapping</strong>
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<p>Neufeld et al. (1997, 1997) performed homozygosity mapping and linkage mapping in 4 large kindreds of native Alaskan and Italian origin with TRMA. Strong evidence for linkage was found to a single marker on 1q23.2-q23.3; maximum lod = 3.7 for D1S1679. Sixteen markers spanning the region were examined in the Alaskan kindred, plus 2 additional consanguineous kindreds of Arab-Israeli origin. These results confirmed the putative disease gene interval, suggesting genetic homogeneity. Linkage analysis generated the highest combined lod score, 8.1 at theta = 0.0, with marker D1S2779. The Italian and Alaskan patients shared no haplotypes with each other nor with the Arab-Israeli families, suggesting that the disease arose independently on 3 different genetic backgrounds. Several heterozygous parents had diabetes mellitus, deafness, or megaloblastic anemia, raising the possibility that mutations at this locus predispose carriers to these manifestations. </p><p>Based on genetic recombination, homozygosity mapping, and linkage disequilibrium (highest lod score of 12.5 at D1S2799, at a recombination fraction of 0), Raz et al. (1998) further narrowed the TRMA interval to 4 cM. They analyzed an additional 7 families of diverse ethnic origin and confirmed homogeneity of the disease. </p><p>Banikazemi et al. (1999) narrowed the location of the TRMA locus to a 1.4-cM interval on 1q23.3. Using a P1-derived artificial chromosome (PAC) contig spanning the TRMA candidate region, Labay et al. (1999) clarified the order of genetic markers across the TRMA locus, provided 9 new polymorphic markers, and narrowed the locus to an approximately 400-kb region. </p>
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<strong>Inheritance</strong>
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<p>The transmission pattern of TRMA in the families reported by Labay et al. (1999) was consistent with autosomal recessive inheritance. </p>
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<strong>Molecular Genetics</strong>
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<p>By positional cloning, Labay et al. (1999) identified the SLC19A2 gene, which they called THTR1, within the critical TRMA locus region. In all affected members of 6 families segregating TRMA, they identified homozygous mutations in the SLC19A2 gene, which encodes a putative transmembrane protein homologous to the reduced folate carrier proteins. Labay et al. (1999) suggested that a defective thiamine transporter protein underlies the TRMA syndrome. They noted that studies by Rindi et al. (1994) and by Stagg et al. (1999) had suggested that deficiency in a high-affinity thiamine transporter may cause this disorder. </p><p>Scharfe et al. (2000) reported a girl with a trp358-to-ter mutation (603941.0009) in the SLC19A2 gene. In addition to TRMA, the girl had short stature, hepatosplenomegaly, retinal degeneration, and a brain MRI lesion. Biochemical analyses of muscle and skin biopsies revealed a severe deficiency of pyruvate dehydrogenase and complex I of the respiratory chain. These biochemical abnormalities responded to thiamine supplementation. </p>
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<strong>See Also:</strong>
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Duran and Wadman (1985)
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<strong>REFERENCES</strong>
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Abboud, M. R., Alexander, D., Najjar, S. S.
<strong>Diabetes mellitus, thiamine-dependent megaloblastic anemia, and sensorineural deafness associated with deficient alpha-ketoglutarate dehydrogenase activity.</strong>
J. Pediat. 107: 537-541, 1985.
[PubMed: 4045602]
[Full Text: https://doi.org/10.1016/s0022-3476(85)80011-1]
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<p class="mim-text-font">
Banikazemi, M., Diaz, G. A., Voussough, P., Jalali, M., Desnick, R. J., Gelb, B. D.
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[Full Text: https://doi.org/10.1006/mgme.1998.2799]
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Bazarbachi, A., Muakkit, S., Ayas, M., Taher, A., Salem, Z., Solh, H., Haidar, J. H.
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Brit. J. Haemat. 102: 1098-1100, 1998.
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Bergmann, A. K., Sahai, I., Falcone, J. F., Fleming, J., Bagg, A., Borgna-Pignati, C., Casey, R., Fabris, L, Hexner, E., Mathews, L., Ribeiro, M. L., Wierenga, K. J., Neufeld, E. J.
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Borgna-Pignatti, C., Marradi, P., Pinelli, L., Monetti, N., Patrini, C.
<strong>Thiamine-responsive anemia in DIDMOAD syndrome.</strong>
J. Pediat. 114: 405-410, 1989.
[PubMed: 2537896]
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Burgess, R. C.
<strong>Infantile beriberi.</strong>
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Duran, M., Wadman, S. K.
<strong>Thiamine-responsive inborn errors of metabolism.</strong>
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[PubMed: 3930844]
[Full Text: https://doi.org/10.1007/BF01800663]
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Haworth, C., Evans, D. I. K., Mitra, J., Wickramasinghe, S. N.
<strong>Thiamine responsive anaemia: a study of two further cases.</strong>
Brit. J. Haemat. 50: 549-561, 1982.
[PubMed: 6175336]
[Full Text: https://doi.org/10.1111/j.1365-2141.1982.tb01955.x]
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Labay, V., Raz, T., Baron, D., Mandel, H., Williams, H., Barrett, T., Szargel, R., McDonald, L., Shalata, A., Nosaka, K., Gregory, S., Cohen, N.
<strong>Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness.</strong>
Nature Genet. 22: 300-304, 1999.
[PubMed: 10391221]
[Full Text: https://doi.org/10.1038/10372]
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Mandel, H., Berant, M., Hazani, A., Naveh, Y.
<strong>Thiamine-dependent beriberi in the &#x27;thiamine-responsive anemia syndrome.&#x27;.</strong>
New Eng. J. Med. 311: 836-838, 1984.
[PubMed: 6472386]
[Full Text: https://doi.org/10.1056/NEJM198409273111307]
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Neufeld, E. J., Mandel, H., Raz, T., Szargel, R., Yandava, C. N., Stagg, A., Faure, S., Barrett, T., Buist, N., Cohen, N.
<strong>Localization of the gene for thiamine-responsive megaloblastic anemia syndrome, on the long arm of chromosome 1, by homozygosity mapping.</strong>
Am. J. Hum. Genet. 61: 1335-1341, 1997.
[PubMed: 9399900]
[Full Text: https://doi.org/10.1086/301642]
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Neufeld, E. J., Mandel, H., Raz, T., Yandava, C. N., Szargel, R., Stagg, A., Faure, S., Barrett, T. G., Cohen, N.
<strong>Localization of the gene for the syndrome of thiamine-responsive megaloblastic anemia with diabetes and deafness to chromosome 1q23 by homozygosity mapping. (Abstract)</strong>
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Poggi, V., Longo, G., DeVizia, B., Andria, G., Rindi, G., Patrini, C., Cassandro, E.
<strong>Thiamin-responsive megaloblastic anaemia: a disorder of thiamin transport?</strong>
J. Inherit. Metab. Dis. 7 (suppl. 2): 153-154, 1984.
[PubMed: 6090807]
[Full Text: https://doi.org/10.1007/978-94-009-5612-4_51]
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Poggi, V., Rindi, G., Patrini, C., De Vizia, B., Longo, G., Andria, G.
<strong>Studies on thiamine metabolism in thiamine-responsive megaloblastic anaemia.</strong>
Europ. J. Pediat. 148: 307-311, 1989.
[PubMed: 2540004]
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<strong>Refined mapping of the gene for thiamine-responsive megaloblastic anemia syndrome and evidence for genetic homogeneity.</strong>
Hum. Genet. 103: 455-461, 1998.
[PubMed: 9856490]
[Full Text: https://doi.org/10.1007/s004390050850]
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Rindi, G., Casirola, D., Poggi, V., De Vizia, B., Patrini, C., Laforenza, U.
<strong>Thiamine transport by erythrocytes and ghosts in thiamine-responsive megaloblastic anaemia.</strong>
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[PubMed: 1326679]
[Full Text: https://doi.org/10.1007/BF01799637]
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Rindi, G., Patrini, C., Laforenza, U., Mandel, H., Berant, M., Viana, M. B., Poggi, V., Zarra, A. N.
<strong>Further studies on erythrocyte thiamin transport and phosphorylation in seven patients with thiamin-responsive megaloblastic anaemia.</strong>
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Rogers, L. E., Porter, F. S., Sidbury, J. B., Jr.
<strong>Thiamine-responsive megaloblastic anemia.</strong>
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[PubMed: 5767338]
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Scharfe, C., Hauschild, M., Klopstock, T., Janssen, A. J. M., Heidemann, P. H., Meitinger, T., Jaksch, M.
<strong>A novel mutation in the thiamine responsive megaloblastic anaemia gene SLC19A2 in a patient with deficiency of respiratory chain complex I.</strong>
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[PubMed: 10978358]
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Stagg, A. R., Fleming, J. C., Baker, M. A., Sakamoto, M., Cohen, N., Neufeld, E. J.
<strong>Defective high-affinity thiamine transporter leads to cell death in thiamine-responsive megaloblastic anemia syndrome fibroblasts.</strong>
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[PubMed: 10074490]
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Viana, M. B., Carvalho, R. I.
<strong>Thiamine-responsive megaloblastic anemia, sensorineural deafness, and diabetes mellitus: a new syndrome?</strong>
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[PubMed: 671156]
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Villa, V., Rivellese, A., Di Salle, F., Iovine, C., Poggi, V., Capaldo, B.
<strong>Acute ischemic stroke in a young woman with the thiamine-responsive megaloblastic anemia syndrome.</strong>
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[PubMed: 10720020]
[Full Text: https://doi.org/10.1210/jcem.85.3.6419]
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Cassandra L. Kniffin - updated : 2/8/2012<br>Michael J. Wright - updated : 8/9/2001<br>John A. Phillips, III - updated : 2/27/2001<br>Victor A. McKusick - updated : 6/24/1999<br>Ada Hamosh - updated : 3/10/1999<br>Victor A. McKusick - updated : 2/19/1999<br>Victor A. McKusick - updated : 2/16/1998<br>Victor A. McKusick - updated : 10/22/1997
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