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Entry
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- #261630 - HYPERPHENYLALANINEMIA, BH4-DEFICIENT, C; HPABH4C
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- OMIM
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<p>
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<span class="h4">#261630</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<li role="presentation">
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<a href="/clinicalSynopsis/261630"><strong>Clinical Synopsis</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#diagnosis">Diagnosis</a>
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<a href="#clinicalManagement">Clinical Management</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#seeAlso"><strong>See Also</strong></a>
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<li role="presentation">
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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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<a href="#editHistory"><strong>Edit History</strong></a>
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<div style="display: table-cell;">External Links</div>
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</a>
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</h4>
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
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<div style="display: table-cell;">Clinical Resources</div>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div><a href="https://clinicaltrials.gov/search?cond=(HYPERPHENYLALANINEMIA, BH4-DEFICIENT, C) OR (QDPR)" class="mim-tip-hint" title="Clinical Trials" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="#mimEuroGentestFold" id="mimEuroGentestToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="A list of European laboratories that offer genetic testing."><span id="mimEuroGentestToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>EuroGentest</div>
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<div id="mimEuroGentestFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=457&Typ=Pat" title="Dihydropteridine reductase deficiency" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Dihydropteridine reductase… </a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=19279&Typ=Pat" title="Hyperphenylalaninemia due to tetrahydrobiopterin deficiency" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">Hyperphenylalaninemia due … </a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/5716" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=261630[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div><a href="#mimNewbornScreeningFold" id="mimNewbornScreeningToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="Information and resources for newborn screening and genetics."><span id="mimNewbornScreeningToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Newborn Screening</div>
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<div id="mimNewbornScreeningFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.acmg.net/PDFLibrary/Phenylalanine.pdf" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Newborn Screening', 'domain': 'www.acmg.net'})">ACMG ACT Sheet</a></div><div style="margin-left: 0.5em;"><a href="https://www.acmg.net/PDFLibrary/Phenylalanine-Algorithm.pdf" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Newborn Screening', 'domain': 'www.acmg.net'})">ACMG Algorithm</a></div>
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<div><a href="#mimOrphanetFold" id="mimOrphanetToggle" data-toggle="collapse" class="mim-tip-hint mimTriangleToggle" title="European reference portal for information on rare diseases and orphan drugs."><span id="mimOrphanetToggleTriangle" class="small" style="margin-left: -0.8em;">►</span>Orphanet</div>
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<div id="mimOrphanetFold" class="collapse">
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<div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=226" title="Dihydropteridine reductase deficiency" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Dihydropteridine reductase…</a></div><div style="margin-left: 0.5em;"><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=238583" title="Hyperphenylalaninemia due to tetrahydrobiopterin deficiency" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">Hyperphenylalaninemia due …</a></div>
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</div>
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<div class="panel-heading mim-panel-heading" role="tab" id="mimVariation">
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<span class="panel-title">
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<a href="#mimVariationLinksFold" id="mimVariationLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<span id="mimVariationLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5">►</span> Variation
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<div id="mimVariationLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div><a href="http://www.bh4.org/" class="mim-tip-hint" title="A gene-specific database of variation." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Locus Specific DB', 'domain': 'locus-specific-db.org'})">Locus Specific DBs</a></div>
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<div class="panel-heading mim-panel-heading" role="tab" id="mimAnimalModels">
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<span class="panel-title">
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<span class="small">
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<a href="#mimAnimalModelsLinksFold" id="mimAnimalModelsLinksToggle" class="collapsed mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimAnimalModelsLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">►</div>
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<div style="display: table-cell;">Animal Models</div>
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</a>
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<div id="mimAnimalModelsLinksFold" class="panel-collapse collapse mimLinksFold" role="tabpanel">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://www.alliancegenome.org/disease/DOID:0081130" class="mim-tip-hint" title="Search Across Species; explore model organism and human comparative genomics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Alliance Genome', 'domain': 'alliancegenome.org'})">Alliance Genome</a></div>
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<div><a href="http://www.informatics.jax.org/disease/261630" class="mim-tip-hint" title="Phenotypes, alleles, and disease models from Mouse Genome Informatics." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MGI Mouse Phenotype', 'domain': 'informatics.jax.org'})">MGI Mouse Phenotype</a></div>
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<div><a href="https://wormbase.org/resources/disease/DOID:0081130" 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>
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<span class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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</div>
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<div>
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<a id="title" class="mim-anchor"></a>
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<div>
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<a id="number" class="mim-anchor"></a>
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<div class="text-right">
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<a href="#" class="mim-tip-icd" qtip_title="<strong>ICD+</strong>" qtip_text="
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<strong>SNOMEDCT:</strong> 58256000<br />
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<strong>ORPHA:</strong> 226, 238583<br />
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<strong>DO:</strong> 0081130<br />
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">ICD+</a>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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261630
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</span>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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HYPERPHENYLALANINEMIA, BH4-DEFICIENT, C; HPABH4C
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</span>
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</h3>
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</div>
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<div>
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<br />
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<p>
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<em>Alternative titles; symbols</em>
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<div>
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<h4>
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<span class="mim-font">
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HYPERPHENYLALANINEMIA, TETRAHYDROBIOPTERIN-DEFICIENT, DUE TO DHPR DEFICIENCY<br />
|
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DIHYDROPTERIDINE REDUCTASE DEFICIENCY<br />
|
|
DHPR DEFICIENCY<br />
|
|
QUINOID DIHYDROPTERIDINE REDUCTASE DEFICIENCY<br />
|
|
QDPR DEFICIENCY
|
|
</span>
|
|
</h4>
|
|
</div>
|
|
</div>
|
|
<div>
|
|
<br />
|
|
</div>
|
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|
|
|
|
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</div>
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|
|
|
|
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|
|
|
|
|
<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/4/115?start=-3&limit=10&highlight=115">
|
|
4p15.32
|
|
</a>
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
Hyperphenylalaninemia, BH4-deficient, C
|
|
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/261630"> 261630 </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">
|
|
QDPR
|
|
</span>
|
|
</td>
|
|
<td>
|
|
<span class="mim-font">
|
|
<a href="/entry/612676"> 612676 </a>
|
|
</span>
|
|
</td>
|
|
</tr>
|
|
|
|
</tbody>
|
|
</table>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
|
|
|
|
<div class="btn-group ">
|
|
<a href="/clinicalSynopsis/261630" class="btn btn-warning" role="button"> Clinical Synopsis </a>
|
|
<button type="button" id="mimPhenotypicSeriesToggle" class="btn btn-warning dropdown-toggle mimSingletonFoldToggle" data-toggle="collapse" href="#mimClinicalSynopsisFold" onclick="ga('send', 'event', 'Unfurl', 'ClinicalSynopsis', 'omim.org')">
|
|
<span class="caret"></span>
|
|
<span class="sr-only">Toggle Dropdown</span>
|
|
</button>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div class="btn-group">
|
|
<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
|
PheneGene Graphics <span class="caret"></span>
|
|
</button>
|
|
<ul class="dropdown-menu" style="width: 17em;">
|
|
<li><a href="/graph/linear/261630" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
|
|
<li><a href="/graph/radial/261630" 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> Other </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Poor feeding in infancy <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/299698007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">299698007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0576456&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0576456</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> Head </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Microcephaly <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1148757008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1148757008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/Q02" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">Q02</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/742.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">742.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C4551563&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C4551563</a>, <a href="https://bioportal.bioontology.org/search?q=C0025958&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025958</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000252" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000252</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Microcephaly-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=0584d323b99dcd7001cc50e224947aca" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Mouth </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Hypersalivation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/53827007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">53827007</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K11.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K11.7</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0037036&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0037036</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002307" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002307</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0003781" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003781</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003781" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003781</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> ABDOMEN </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Gastrointestinal </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Swallowing difficulties <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/288939007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">288939007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/40739000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">40739000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R13.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R13.1</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/R13.10" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R13.10</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/787.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.2</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/787.20" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.20</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011168&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011168</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002015" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002015</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002015" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002015</a>]</span><br />
|
|
|
|
</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">
|
|
|
|
- Delayed development <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 /> -
|
|
Psychomotor retardation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/398991009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">398991009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/1144814003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">1144814003</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0424230&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0424230</a>, <a href="https://bioportal.bioontology.org/search?q=C5441816&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C5441816</a>]</span><br /> -
|
|
Mental retardation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/228156007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">228156007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/110359009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">110359009</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/317-319.99" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">317-319.99</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714756&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714756</a>, <a href="https://bioportal.bioontology.org/search?q=C0025362&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0025362</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001249" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001249</a>]</span><br /> -
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Hypotonia, truncal <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853743&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853743</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008936" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008936</a>]</span><br /> -
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Hypertonia of the extremities <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749427&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749427</a>]</span><br /> -
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Uncoordinated movements <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749428&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749428</a>]</span><br /> -
|
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Tremor <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/26079004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">26079004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R25.1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R25.1</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0040822&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0040822</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001337" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001337</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001337" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001337</a>]</span><br /> -
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Dystonia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/15802004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">15802004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G24.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G24.9</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/G24" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G24</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0013421&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0013421</a>, <a href="https://bioportal.bioontology.org/search?q=C0393593&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0393593</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001332" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001332</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001332" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001332</a>]</span><br /> -
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Seizures <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/91175000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">91175000</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0036572&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0036572</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001250" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001250</a>]</span><br /> -
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Choreoathetosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/43105007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">43105007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0085583&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085583</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001266" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001266</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001266" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001266</a>]</span><br /> -
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Intracerebral calcifications <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/17944005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">17944005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0270685&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0270685</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002514" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002514</a>, <a href="https://hpo.jax.org/app/browse/term/HP:0430048" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0430048</a>]</span><br />
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</span>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<em> Behavioral Psychiatric Manifestations </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Irritability <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/55929007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">55929007</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/799.22" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">799.22</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0022107&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0022107</a>, <a href="https://bioportal.bioontology.org/search?q=C2700617&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2700617</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000737" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000737</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000737" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000737</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> METABOLIC FEATURES </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Hyperthermia, episodic <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/77957000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">77957000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/A68" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">A68</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C3714772&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C3714772</a>, <a href="https://bioportal.bioontology.org/search?q=C0277799&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0277799</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001954" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001954</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001954" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001954</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/780.60" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">780.60</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> LABORATORY ABNORMALITIES </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Hyperphenylalaninemia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/68528007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">68528007</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0751435&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0751435</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004923" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004923</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0004923" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0004923</a>]</span><br /> -
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Decreased homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) in CSF <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749430&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749430</a>]</span><br /> -
|
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Increased biopterin in urine and CSF <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749441&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749441</a>]</span><br /> -
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Decreased or absent dihydropteridine reductase activity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C2749442&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2749442</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MISCELLANEOUS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Onset in infancy <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1848924&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1848924</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003593" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003593</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003593" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003593</a>]</span><br /> -
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Variable severity <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1861403&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1861403</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003828" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003828</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003828" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003828</a>]</span><br /> -
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Progressive neurologic deterioration if untreated<br /> -
|
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Diurnal fluctuation of neurologic symptoms<br /> -
|
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Defect in tetrahydrobiopterin (BH4) synthesis<br /> -
|
|
Treatment with BH4 is effective<br /> -
|
|
Neurotransmitter treatment with L-dopa and serotonin or precursors is effective<br /> -
|
|
Early treatment can reduce neurologic symptoms<br />
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</span>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> MOLECULAR BASIS </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Caused by mutation in the quinoid dihydropteridine reductase gene (QDPR, <a href="/entry/612676#0001">612676.0001</a>)<br />
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</span>
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</div>
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</div>
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</div>
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<div class="text-right">
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<a href="#mimClinicalSynopsisFold" data-toggle="collapse">▲ Close</a>
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</div>
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<div>
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<br />
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<div>
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<a id="text" class="mim-anchor"></a>
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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</h4>
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<p>A number sign (#) is used with this entry because tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia (HPA) due to dihydropteridine reductase deficiency (HPABH4C) is caused by homozygous or compound heterozygous mutation in the QDPR gene (<a href="/entry/612676">612676</a>), which encodes an enzyme involved in the salvage pathway for BH4, on chromosome 4p15.</p><p>For a general phenotypic description and a discussion of genetic heterogeneity of BH4-deficient hyperphenylalaninemia, see HPABH4A (<a href="/entry/261640">261640</a>).</p>
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<p><a href="#18" class="mim-tip-reference" title="Smith, I., Clayton, B. E., Wolff, O. H. <strong>New variant of phenylketonuria with progressive neurological illness unresponsive to phenylalanine restriction.</strong> Lancet 305: 1108-1111, 1975. Note: Originally Volume I.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/49470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">49470</a>] [<a href="https://doi.org/10.1016/s0140-6736(75)92498-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="49470">Smith et al. (1975)</a> described 3 children, 2 of them sibs, with an unusual type of phenylketonuria. All 3 (2 of them observed from the neonatal period) had a progressive neurologic illness that did not respond to a low phenylalanine diet, unlike classic PKU (<a href="/entry/261600">261600</a>). The biochemical features suggested that the block in conversion of phenylalanine to tyrosine was less severe than in classic PKU. Phenylalanine hydroxylase (PAH; <a href="/entry/612349">612349</a>), measured in 1 patient, was normal. <a href="#18" class="mim-tip-reference" title="Smith, I., Clayton, B. E., Wolff, O. H. <strong>New variant of phenylketonuria with progressive neurological illness unresponsive to phenylalanine restriction.</strong> Lancet 305: 1108-1111, 1975. Note: Originally Volume I.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/49470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">49470</a>] [<a href="https://doi.org/10.1016/s0140-6736(75)92498-8" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="49470">Smith et al. (1975)</a> suggested that the patients had a disorder of biopterin metabolism possibly due to a defect in the enzyme dihydropteridine reductase. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=49470" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#1" class="mim-tip-reference" title="Butler, I. J., Holtzman, N. A., Kaufman, S., Koslow, S. H., Krumholz, A., Milstien, S. <strong>Phenylketonuria due to deficiency of dihydropteridine reductase. (Abstract)</strong> Pediat. Res. 9: 348, 1975."None>Butler et al. (1975)</a> reported dihydropteridine reductase deficiency in a patient unresponsive to dietary treatment. Biopterin is the natural cofactor for phenylalanine hydroxylase. In its active tetra-hydro form (BH4), biopterin donates hydrogen ions during the hydroxylation reaction. The same cofactor system is active in neural tissue for hydroxylation of tyrosine to dihydroxyphenylalanine (levodopa) in the synthesis of amine transmitters (dopaminine, noradrenaline, and adrenaline) and serotonin. Phenylalanine restriction would not be expected to help the neurologic problem. Basal ganglion symptoms can be related to the importance of levodopa and dopamine to that part of the brain.</p><p><a href="#12" class="mim-tip-reference" title="Kaufman, S., Holtzman, N. A., Milstien, S., Butler, I. J., Krumholz, A. <strong>Phenylketonuria due to a deficiency of dihydropteridine reductase.</strong> New Eng. J. Med. 293: 785-790, 1975.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1160969/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1160969</a>] [<a href="https://doi.org/10.1056/NEJM197510162931601" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1160969">Kaufman et al. (1975)</a> demonstrated absence of dihydropteridine reductase in liver, brain, and cultured skin fibroblasts of a patient with elevated blood phenylalanine and no response to diet despite good control of blood levels. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=1160969" 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="#20" class="mim-tip-reference" title="Watts, R. W. E., Purkiss, P., Chalmers, R. A. <strong>A new variant form of phenylketonuria.</strong> Quart. J. Med. 48: 403-417, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/317358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">317358</a>]" pmid="317358">Watts et al. (1979)</a> reported a patient with hyperphenylalaninemia who had better tolerance of phenylalanine compared to patients with classic PKU. However, unlike patients with classic PKU, treatment with trimethoprim reduced the phenylalanine tolerance in this patient. Since trimethoprim inhibits 7,8-dihydrobiopterin reduction, <a href="#20" class="mim-tip-reference" title="Watts, R. W. E., Purkiss, P., Chalmers, R. A. <strong>A new variant form of phenylketonuria.</strong> Quart. J. Med. 48: 403-417, 1979.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/317358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">317358</a>]" pmid="317358">Watts et al. (1979)</a> speculated that the causative defect may involve the gene for dihydropteridine reductase such that it is sensitive to the reduced availability of tetrahydrobiopterin produced by trimethoprim. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=317358" 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="#21" class="mim-tip-reference" title="Woody, R. C., Brewster, M. A., Glasier, C. <strong>Progressive intracranial calcification in dihydropteridine reductase deficiency prior to folinic acid therapy.</strong> Neurology 39: 673-675, 1989.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2785251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2785251</a>] [<a href="https://doi.org/10.1212/wnl.39.5.673" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2785251">Woody et al. (1989)</a> pointed out that without folinic acid therapy as a source of tetrahydrofolate, patients with DHPR deficiency show progressive basal ganglia and other subcortical calcification. The pattern of calcification resembled that seen in CNS folate deficiency, both that in the congenital form (<a href="/entry/229050">229050</a>) and that in the methotrexate-induced form. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2785251" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#13" class="mim-tip-reference" title="Larnaout, A., Belal, S., Miladi, N., Kaabachi, N., Mebazza, A., Dhondt, J. L., Hentati, F. <strong>Juvenile form of dihydropteridine reductase deficiency in 2 Tunisian patients.</strong> Neuropediatrics 29: 322-323, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10029353/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10029353</a>] [<a href="https://doi.org/10.1055/s-2007-973586" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10029353">Larnaout et al. (1998)</a> described 2 brothers with juvenile-onset DHPR deficiency. Both were considered normal until 6 years of age when they developed a fluctuating and progressive encephalopathy combining mental retardation, epilepsy, and pyramidal, cerebellar, and extrapyramidal signs. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=10029353" 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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Dahl et al. (<a href="#2" class="mim-tip-reference" title="Dahl, H.-H. M., Hutchinson, W., McAdam, W., Wake, S., Morgan, F. J., Cotton, R. G. H. <strong>Human dihydropteridine reductase: characterisation of a cDNA clone and its use in analysis of patients with dihydropteridine reductase deficiency.</strong> Nucleic Acids Res. 15: 1921-1932, 1987.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/3031582/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">3031582</a>] [<a href="https://doi.org/10.1093/nar/15.5.1921" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="3031582">1987</a>, <a href="#3" class="mim-tip-reference" title="Dahl, H.-H. M., Wake, S., Cotton, R. G. H., Danks, D. M. <strong>The use of restriction fragment length polymorphisms in prenatal diagnosis of dihydropteridine reductase deficiency.</strong> J. Med. Genet. 25: 25-28, 1988.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2895188/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2895188</a>] [<a href="https://doi.org/10.1136/jmg.25.1.25" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="2895188">1988</a>) showed that RFLPs of the DHPR locus could be used for prenatal diagnosis. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=2895188+3031582" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#5" class="mim-tip-reference" title="Danks, D. M., Cotton, R. G. H., Schlesinger, P. <strong>Tetrahydrobiopterin treatment of variant form of phenylketonuria. (Letter)</strong> Lancet 306: 1043 only, 1975. Note: Originally Volume II.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/53532/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">53532</a>] [<a href="https://doi.org/10.1016/s0140-6736(75)90335-9" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="53532">Danks et al. (1975)</a> found that intravenous tetrahydrobiopterin (BH4) treatment was effective and resulted in a fall in serum phenylalanine. Oral therapy had no effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=53532" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>In a patient with dihydropteridine reductase deficiency, the offspring of consanguineous parents, <a href="#11" class="mim-tip-reference" title="Howells, D. W., Forrest, S. M., Dahl, H.-H. M., Cotton, R. G. H. <strong>Insertion of an extra codon for threonine is a cause of dihydropteridine reductase deficiency.</strong> Am. J. Hum. Genet. 47: 279-285, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2116088/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2116088</a>]" pmid="2116088">Howells et al. (1990)</a> identified homozygosity for a mutation in the QDPR gene (<a href="/entry/612676#0001">612676.0001</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2116088" 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="Smooker, P. M., Cotton, R. G. H. <strong>Molecular basis of dihydropteridine reductase deficiency.</strong> Hum. Mutat. 5: 279-284, 1995.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7627180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7627180</a>] [<a href="https://doi.org/10.1002/humu.1380050402" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="7627180">Smooker and Cotton (1995)</a> reviewed 12 point mutations that had been described in DHPR cDNA, all of which resulted in dihydropteridine reductase deficiency. The mutations resulted in amino acid substitutions, insertions, or premature terminations. A further 2 mutations resulted in aberrant splicing of QDPR transcripts. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7627180" 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="#17" class="mim-tip-reference" title="Romstad, A., Kalkanoglu, H. S., Coskun, T., Demirkol, M., Tokatli, A., Dursun, A., Baykal, T., Ozalp, I., Guldberg, P., Guttler, F. <strong>Molecular analysis of 16 Turkish families with DHPR deficiency using denaturing gradient gel electrophoresis (DGGE).</strong> Hum. Genet. 107: 546-553, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/11153907/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">11153907</a>] [<a href="https://doi.org/10.1007/s004390000407" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="11153907">Romstad et al. (2000)</a> studied 17 patients belonging to 16 Turkish families with DHPR deficiency. The patients were detected at neonatal screening for hyperphenylalaninemia or upon the development of neurologic symptoms. A mutation screen of the entire open reading frame and all splice sites of the QDPR gene identified 10 different mutations, 7 of which were novel (e.g., <a href="/entry/612676#0007">612676.0007</a>). Six of the mutations were missense, 2 were nonsense, and 2 were frameshift mutations. All patients had homoallelic genotypes, which allowed the establishment of genotype-phenotype associations. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=11153907" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a href="#Danks1978" class="mim-tip-reference" title="Danks, D. M., Bartholome, K., Clayton, B. E., Curtius, H., Grobe, H., Lemming, R., Pfleiderer, W., Rembold, H., Rey, F. <strong>Malignant hyperphenylalaninaemia--current status (June 1977).</strong> J. Inherit. Metab. Dis. 1: 49-53, 1978.">Danks et al. (1978)</a>; <a href="#Danks1979" class="mim-tip-reference" title="Danks, D. M., Schlesinger, P., Firgaira, F., Cotton, R. G. H., Watson, B. M., Rembold, H., Hennings, G. <strong>Malignant hyperphenylalaninemia--clinical features, biochemical findings, and experience with administration of biopterins.</strong> Pediat. Res. 13: 1150-1155, 1979.">Danks et al. (1979)</a>; <a href="#Dianzani1998" class="mim-tip-reference" title="Dianzani, I., de Sanctis, L., Smooker, P. M., Gough, T. J., Alliaudi, C., Brusco, A., Spada, M., Blau, N., Dobos, M., Zhang, H.-P., Yang, N., Ponzone, A., Armarego, W. L. F., Cotton, R. G. H. <strong>Dihydropteridine reductase deficiency: physical structure of the QDPR gene, identification of two new mutations and genotype-phenotype correlations.</strong> Hum. Mutat. 12: 267-273, 1998.">Dianzani et al. (1998)</a>; <a href="#Firgaira1980" class="mim-tip-reference" title="Firgaira, F. A., Cotton, R. G. H., Danks, D. M. <strong>Dihydropteridine reductase deficiency: diagnosis by assay on peripheral blood cells. (Letter)</strong> Lancet 315: 160 only, 1980. Note: Originally Volume I.">Firgaira et al. (1980)</a>; <a href="#Firgaira1979" class="mim-tip-reference" title="Firgaira, F. A., Cotton, R. G. H., Danks, D. M. <strong>Dihydropteridine reductase deficiency: diagnosis by assays on peripheral blood-cells.</strong> Lancet 314: 1260-1263, 1979. Note: Originally Volume II.">Firgaira et al. (1979)</a>; <a href="#Grobe1978" class="mim-tip-reference" title="Grobe, H., Bartholome, K., Milstien, S., Kaufman, S. <strong>Hyperphenylalaninaemia due to dihydropteridine reductase deficiency.</strong> Europ. J. Pediat. 129: 93-98, 1978.">Grobe et al. (1978)</a>; <a href="#Longhi1985" class="mim-tip-reference" title="Longhi, R., Riva, E., Valsasina, R., Paccanelli, S., Giovannini, M. <strong>Phenylketonuria due to dihydropteridine reductase deficiency: presentation of two cases.</strong> J. Inherit. Metab. Dis. 8 (suppl. 2): 97-98, 1985.">Longhi et al. (1985)</a>; <a href="#Milstien1976" class="mim-tip-reference" title="Milstien, S., Holtzman, N. A., O'Flynn, M. E., Thomas, G. H., Butler, I. J., Kaufman, S. <strong>Hyperphenylalaninemia due to dihydropteridine reductase deficiency: assay of the enzyme in fibroblasts from affected infants, heterozygotes, and in normal amniotic fluid cells.</strong> J. Pediat. 89: 763-766, 1976.">Milstien et al. (1976)</a>; <a href="#Milstien1980" class="mim-tip-reference" title="Milstien, S., Kaufman, S., Summer, G. K. <strong>Hyperphenylalaninemia due to dihydropteridine reductase deficiency: diagnosed by measurement of oxidized and reduced pterins in urine.</strong> Pediatrics 65: 806-810, 1980.">Milstien et al. (1980)</a>
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[<a href="https://doi.org/10.1136/jmg.25.1.25" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF01801843" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0140-6736(75)90335-9" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1203/00006450-197910000-00014" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1002/(SICI)1098-1004(1998)12:4<267::AID-HUMU8>3.0.CO;2-C" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0140-6736(80)90648-0" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0140-6736(79)92279-7" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF00442368" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1056/NEJM197510162931601" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1055/s-2007-973586" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF01811476" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/s0022-3476(76)80798-6" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/49470/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">49470</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=49470" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/s0140-6736(75)92498-8" target="_blank">Full Text</a>]
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<a id="19" class="mim-anchor"></a>
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<a id="Smooker1995" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Smooker, P. M., Cotton, R. G. H.
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<strong>Molecular basis of dihydropteridine reductase deficiency.</strong>
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Hum. Mutat. 5: 279-284, 1995.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/7627180/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">7627180</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=7627180" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1002/humu.1380050402" target="_blank">Full Text</a>]
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</p>
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<a id="20" class="mim-anchor"></a>
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<a id="Watts1979" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Watts, R. W. E., Purkiss, P., Chalmers, R. A.
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<strong>A new variant form of phenylketonuria.</strong>
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Quart. J. Med. 48: 403-417, 1979.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/317358/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">317358</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=317358" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<a id="21" class="mim-anchor"></a>
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<a id="Woody1989" class="mim-anchor"></a>
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<div class="">
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<p class="mim-text-font">
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Woody, R. C., Brewster, M. A., Glasier, C.
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<strong>Progressive intracranial calcification in dihydropteridine reductase deficiency prior to folinic acid therapy.</strong>
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Neurology 39: 673-675, 1989.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/2785251/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">2785251</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=2785251" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1212/wnl.39.5.673" target="_blank">Full Text</a>]
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<a href="#mimCollapseContributors" role="button" data-toggle="collapse"> Contributors: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Cassandra L. Kniffin - updated : 4/10/2009
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<span class="mim-text-font">
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Victor A. McKusick - updated : 12/18/2000<br>Victor A. McKusick - updated : 7/14/1999<br>Victor A. McKusick - updated : 6/2/1999<br>Victor A. McKusick - updated : 9/18/1998
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<div class="col-lg-2 col-md-2 col-sm-4 col-xs-4">
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Creation Date:
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Victor A. McKusick : 6/4/1986
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<a href="#mimCollapseEditHistory" role="button" data-toggle="collapse"> Edit History: </a>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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carol : 05/24/2016
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<span class="mim-text-font">
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carol : 3/26/2015<br>carol : 4/15/2009<br>ckniffin : 4/10/2009<br>carol : 4/1/2009<br>carol : 3/24/2009<br>carol : 3/24/2009<br>terry : 3/24/2009<br>terry : 3/20/2009<br>carol : 3/19/2009<br>terry : 3/13/2009<br>terry : 6/9/2005<br>alopez : 3/17/2004<br>mcapotos : 1/18/2001<br>mcapotos : 1/4/2001<br>terry : 12/18/2000<br>alopez : 11/24/1999<br>jlewis : 8/3/1999<br>jlewis : 7/30/1999<br>jlewis : 7/30/1999<br>terry : 7/14/1999<br>carol : 6/15/1999<br>jlewis : 6/15/1999<br>jlewis : 6/14/1999<br>terry : 6/2/1999<br>carol : 9/23/1998<br>dkim : 9/23/1998<br>terry : 9/18/1998<br>mark : 10/14/1997<br>terry : 10/7/1997<br>mark : 1/22/1996<br>mark : 1/19/1996<br>mark : 7/6/1995<br>davew : 8/19/1994<br>mimadm : 4/14/1994<br>warfield : 3/9/1994<br>carol : 9/27/1993<br>supermim : 3/17/1992
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<h3>
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<span class="mim-font">
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<strong>#</strong> 261630
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</span>
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</h3>
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<div>
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<h3>
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<span class="mim-font">
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HYPERPHENYLALANINEMIA, BH4-DEFICIENT, C; HPABH4C
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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<h4>
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<span class="mim-font">
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HYPERPHENYLALANINEMIA, TETRAHYDROBIOPTERIN-DEFICIENT, DUE TO DHPR DEFICIENCY<br />
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DIHYDROPTERIDINE REDUCTASE DEFICIENCY<br />
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DHPR DEFICIENCY<br />
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QUINOID DIHYDROPTERIDINE REDUCTASE DEFICIENCY<br />
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QDPR DEFICIENCY
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</span>
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<strong>SNOMEDCT:</strong> 58256000;
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<strong>ORPHA:</strong> 226, 238583;
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<strong>DO:</strong> 0081130;
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<h4>
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<span class="mim-font">
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<strong>Phenotype-Gene Relationships</strong>
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</h4>
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<div>
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<table class="table table-bordered table-condensed small mim-table-padding">
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Location
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
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</th>
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<th>
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Inheritance
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<th>
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Phenotype <br /> mapping key
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<th>
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Gene/Locus
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<th>
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Gene/Locus <br /> MIM number
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<span class="mim-font">
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4p15.32
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<td>
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<span class="mim-font">
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Hyperphenylalaninemia, BH4-deficient, C
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</span>
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</td>
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<td>
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<span class="mim-font">
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261630
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<td>
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<span class="mim-font">
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Autosomal recessive
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</span>
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</td>
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<td>
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<span class="mim-font">
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3
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</span>
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</td>
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<td>
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<span class="mim-font">
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QDPR
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</span>
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</td>
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<td>
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<span class="mim-font">
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612676
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<span class="mim-font">
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<strong>TEXT</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>A number sign (#) is used with this entry because tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia (HPA) due to dihydropteridine reductase deficiency (HPABH4C) is caused by homozygous or compound heterozygous mutation in the QDPR gene (612676), which encodes an enzyme involved in the salvage pathway for BH4, on chromosome 4p15.</p><p>For a general phenotypic description and a discussion of genetic heterogeneity of BH4-deficient hyperphenylalaninemia, see HPABH4A (261640).</p>
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<h4>
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<span class="mim-font">
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<strong>Clinical Features</strong>
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</span>
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<span class="mim-text-font">
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<p>Smith et al. (1975) described 3 children, 2 of them sibs, with an unusual type of phenylketonuria. All 3 (2 of them observed from the neonatal period) had a progressive neurologic illness that did not respond to a low phenylalanine diet, unlike classic PKU (261600). The biochemical features suggested that the block in conversion of phenylalanine to tyrosine was less severe than in classic PKU. Phenylalanine hydroxylase (PAH; 612349), measured in 1 patient, was normal. Smith et al. (1975) suggested that the patients had a disorder of biopterin metabolism possibly due to a defect in the enzyme dihydropteridine reductase. </p><p>Butler et al. (1975) reported dihydropteridine reductase deficiency in a patient unresponsive to dietary treatment. Biopterin is the natural cofactor for phenylalanine hydroxylase. In its active tetra-hydro form (BH4), biopterin donates hydrogen ions during the hydroxylation reaction. The same cofactor system is active in neural tissue for hydroxylation of tyrosine to dihydroxyphenylalanine (levodopa) in the synthesis of amine transmitters (dopaminine, noradrenaline, and adrenaline) and serotonin. Phenylalanine restriction would not be expected to help the neurologic problem. Basal ganglion symptoms can be related to the importance of levodopa and dopamine to that part of the brain.</p><p>Kaufman et al. (1975) demonstrated absence of dihydropteridine reductase in liver, brain, and cultured skin fibroblasts of a patient with elevated blood phenylalanine and no response to diet despite good control of blood levels. </p><p>Watts et al. (1979) reported a patient with hyperphenylalaninemia who had better tolerance of phenylalanine compared to patients with classic PKU. However, unlike patients with classic PKU, treatment with trimethoprim reduced the phenylalanine tolerance in this patient. Since trimethoprim inhibits 7,8-dihydrobiopterin reduction, Watts et al. (1979) speculated that the causative defect may involve the gene for dihydropteridine reductase such that it is sensitive to the reduced availability of tetrahydrobiopterin produced by trimethoprim. </p><p>Woody et al. (1989) pointed out that without folinic acid therapy as a source of tetrahydrofolate, patients with DHPR deficiency show progressive basal ganglia and other subcortical calcification. The pattern of calcification resembled that seen in CNS folate deficiency, both that in the congenital form (229050) and that in the methotrexate-induced form. </p><p>Larnaout et al. (1998) described 2 brothers with juvenile-onset DHPR deficiency. Both were considered normal until 6 years of age when they developed a fluctuating and progressive encephalopathy combining mental retardation, epilepsy, and pyramidal, cerebellar, and extrapyramidal signs. </p>
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<div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Diagnosis</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p><strong><em>Prenatal Diagnosis</em></strong></p><p>
|
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Dahl et al. (1987, 1988) showed that RFLPs of the DHPR locus could be used for prenatal diagnosis. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Clinical Management</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>Danks et al. (1975) found that intravenous tetrahydrobiopterin (BH4) treatment was effective and resulted in a fall in serum phenylalanine. Oral therapy had no effect. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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</div>
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<span class="mim-text-font">
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<p>In a patient with dihydropteridine reductase deficiency, the offspring of consanguineous parents, Howells et al. (1990) identified homozygosity for a mutation in the QDPR gene (612676.0001). </p><p>Smooker and Cotton (1995) reviewed 12 point mutations that had been described in DHPR cDNA, all of which resulted in dihydropteridine reductase deficiency. The mutations resulted in amino acid substitutions, insertions, or premature terminations. A further 2 mutations resulted in aberrant splicing of QDPR transcripts. </p><p>Romstad et al. (2000) studied 17 patients belonging to 16 Turkish families with DHPR deficiency. The patients were detected at neonatal screening for hyperphenylalaninemia or upon the development of neurologic symptoms. A mutation screen of the entire open reading frame and all splice sites of the QDPR gene identified 10 different mutations, 7 of which were novel (e.g., 612676.0007). Six of the mutations were missense, 2 were nonsense, and 2 were frameshift mutations. All patients had homoallelic genotypes, which allowed the establishment of genotype-phenotype associations. </p>
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</span>
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<div>
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<br />
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>See Also:</strong>
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</span>
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</h4>
|
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<span class="mim-text-font">
|
|
Danks et al. (1978); Danks et al. (1979); Dianzani et al. (1998);
|
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Firgaira et al. (1980); Firgaira et al. (1979); Grobe et al. (1978);
|
|
Longhi et al. (1985); Milstien et al. (1976); Milstien et al. (1980)
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</span>
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<div>
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<br />
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</div>
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</div>
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<div>
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<h4>
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<span class="mim-font">
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<strong>REFERENCES</strong>
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</span>
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</h4>
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<div>
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<p />
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</div>
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<div>
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<ol>
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<li>
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<p class="mim-text-font">
|
|
Butler, I. J., Holtzman, N. A., Kaufman, S., Koslow, S. H., Krumholz, A., Milstien, S.
|
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<strong>Phenylketonuria due to deficiency of dihydropteridine reductase. (Abstract)</strong>
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