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Entry
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- #608643 - AROMATIC L-AMINO ACID DECARBOXYLASE DEFICIENCY; AADCD
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- OMIM
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<p>
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<span class="h4">#608643</span>
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<br />
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<strong>Table of Contents</strong>
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<a href="#title"><strong>Title</strong></a>
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<a href="#phenotypeMap"><strong>Phenotype-Gene Relationships</strong></a>
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<a href="/clinicalSynopsis/608643"><strong>Clinical Synopsis</strong></a>
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<a href="#text"><strong>Text</strong></a>
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<a href="#description">Description</a>
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<a href="#clinicalFeatures">Clinical Features</a>
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<a href="#inheritance">Inheritance</a>
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<a href="#biochemicalFeatures">Biochemical Features</a>
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<a href="#diagnosis">Diagnosis</a>
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<a href="#clinicalManagement">Clinical Management</a>
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<a href="#populationGenetics">Population Genetics</a>
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<a href="#molecularGenetics">Molecular Genetics</a>
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<a href="#references"><strong>References</strong></a>
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<a href="#contributors"><strong>Contributors</strong></a>
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<li role="presentation">
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<a href="#creationDate"><strong>Creation Date</strong></a>
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<li role="presentation">
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<a href="#editHistory"><strong>Edit History</strong></a>
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<div style="display: table-cell;">External Links</div>
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</a>
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</h4>
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<span class="panel-title">
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<span class="small">
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<a href="#mimClinicalResourcesLinksFold" id="mimClinicalResourcesLinksToggle" class=" mimSingletonTriangleToggle" role="button" data-toggle="collapse" data-parent="#mimExternalLinksAccordion">
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<div style="display: table-row">
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<div id="mimClinicalResourcesLinksToggleTriangle" class="small mimSingletonTriangle" style="color: #337CB5; display: table-cell;">▼</div>
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<div style="display: table-cell;">Clinical Resources</div>
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</div>
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</a>
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</span>
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<div id="mimClinicalResourcesLinksFold" class="panel-collapse collapse in mimLinksFold" role="tabpanel" aria-labelledby="clinicalResources">
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<div class="panel-body small mim-panel-body">
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<div><a href="https://clinicaltrials.gov/search?cond=AROMATIC L-AMINO ACID DECARBOXYLASE DEFICIENCY" class="mim-tip-hint" title="A registry of federally and privately supported clinical trials conducted in the United States and around the world." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Clinical Trials', 'domain': 'clinicaltrials.gov'})">Clinical Trials</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/ClinicalLabs_Search_Simple.php?lng=EN&LnkId=10397&Typ=Pat" class="mim-tip-hint" title="A list of European laboratories that offer genetic testing." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'EuroGentest', 'domain': 'orpha.net'})">EuroGentest</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/books/NBK595821/" class="mim-tip-hint" title="Expert-authored, peer-reviewed descriptions of inherited disorders including the uses of genetic testing in diagnosis, management, and genetic counseling." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Gene Reviews', 'domain': 'ncbi.nlm.nih.gov'})">Gene Reviews</a></div>
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<div><a href="https://www.diseaseinfosearch.org/x/582" class="mim-tip-hint" title="Network of disease-specific advocacy organizations, universities, private companies, government agencies, and public policy organizations." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'Genetic Alliance', 'domain': 'diseaseinfosearch.org'})">Genetic Alliance</a></div>
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<div><a href="https://medlineplus.gov/genetics/condition/aromatic-l-amino-acid-decarboxylase-deficiency" class="mim-tip-hint" title="Consumer-friendly information about the effects of genetic variation on human health." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'MedlinePlus Genetics', 'domain': 'medlineplus.gov'})">MedlinePlus Genetics</a></div>
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<div><a href="https://www.ncbi.nlm.nih.gov/gtr/all/tests/?term=608643[mim]" class="mim-tip-hint" title="Genetic Testing Registry." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'GTR', 'domain': 'ncbi.nlm.nih.gov'})">GTR</a></div>
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<div><a href="https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=35708" class="mim-tip-hint" title="European reference portal for information on rare diseases and orphan drugs." target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'OrphaNet', 'domain': 'orpha.net'})">OrphaNet</a></div>
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<div 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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</div>
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</a>
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</span>
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</span>
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</div>
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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:0090123" 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/608643" 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:0090123" 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 class="mim-tip-bottom" qtip_title="<strong>Looking for this gene or this phenotype in other resources?</strong>" qtip_text="Select a related resource from the dropdown menu and click for a targeted link to information directly relevant.">
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<div class="col-lg-8 col-lg-pull-2 col-md-8 col-md-pull-2 col-sm-8 col-sm-pull-2 col-xs-12">
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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> 124600004<br />
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<strong>ICD10CM:</strong> E70.81<br />
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<strong>ORPHA:</strong> 35708<br />
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<strong>DO:</strong> 0090123<br />
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">ICD+</a>
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</div>
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<div>
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<span class="h3">
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<span class="mim-font mim-tip-hint" title="Phenotype description, molecular basis known">
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<span class="text-danger"><strong>#</strong></span>
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608643
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</span>
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</span>
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</div>
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</div>
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<div>
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<a id="preferredTitle" class="mim-anchor"></a>
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<h3>
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<span class="mim-font">
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AROMATIC L-AMINO ACID DECARBOXYLASE DEFICIENCY; AADCD
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</span>
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</h3>
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</div>
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<div>
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<br />
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</div>
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<div>
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<a id="alternativeTitles" class="mim-anchor"></a>
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<div>
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<p>
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<span class="mim-font">
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<em>Alternative titles; symbols</em>
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</span>
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</p>
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</div>
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<div>
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<h4>
|
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<span class="mim-font">
|
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AADC DEFICIENCY<br />
|
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DOPA DECARBOXYLASE DEFICIENCY<br />
|
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DDC DEFICIENCY
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</span>
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</h4>
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</div>
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</div>
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<div>
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<br />
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</div>
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</div>
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<div>
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<a id="phenotypeMap" class="mim-anchor"></a>
|
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<h4>
|
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<span class="mim-font">
|
|
<strong>Phenotype-Gene Relationships</strong>
|
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</span>
|
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</h4>
|
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<div>
|
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<table class="table table-bordered table-condensed table-hover small mim-table-padding">
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<thead>
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<tr class="active">
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<th>
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Location
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</th>
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<th>
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Phenotype
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</th>
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<th>
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Phenotype <br /> MIM number
|
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</th>
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<th>
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Inheritance
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</th>
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<th>
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Phenotype <br /> mapping key
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</th>
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<th>
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Gene/Locus
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</th>
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<th>
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Gene/Locus <br /> MIM number
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</th>
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</tr>
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</thead>
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<tbody>
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<tr>
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<td>
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<span class="mim-font">
|
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<a href="/geneMap/7/264?start=-3&limit=10&highlight=264">
|
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7p12.2-p12.1
|
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</a>
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</span>
|
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</td>
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<td>
|
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<span class="mim-font">
|
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Aromatic L-amino acid decarboxylase deficiency
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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<a href="/entry/608643"> 608643 </a>
|
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="Autosomal recessive">AR</abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
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<abbr class="mim-tip-hint" title="3 - The molecular basis of the disorder is known"> 3 </abbr>
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</span>
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</td>
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<td>
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<span class="mim-font">
|
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DDC
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</span>
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</td>
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<td>
|
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<span class="mim-font">
|
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<a href="/entry/107930"> 107930 </a>
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</span>
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</td>
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</tr>
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</tbody>
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</table>
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</div>
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</div>
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<div>
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<div class="btn-group ">
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<a href="/clinicalSynopsis/608643" 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')">
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<span class="caret"></span>
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<span class="sr-only">Toggle Dropdown</span>
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</button>
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</div>
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<div class="btn-group">
|
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<button type="button" class="btn btn-success dropdown-toggle" data-toggle="dropdown" aria-haspopup="true" aria-expanded="false">
|
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PheneGene Graphics <span class="caret"></span>
|
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</button>
|
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<ul class="dropdown-menu" style="width: 17em;">
|
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<li><a href="/graph/linear/608643" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Linear'})"> Linear </a></li>
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<li><a href="/graph/radial/608643" target="_blank" onclick="gtag('event', 'mim_graph', {'destination': 'Radial'})"> Radial </a></li>
|
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</ul>
|
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</div>
|
|
<span class="glyphicon glyphicon-question-sign mim-tip-hint" title="OMIM PheneGene graphics depict relationships between phenotypes, groups of related phenotypes (Phenotypic Series), and genes.<br /><a href='/static/omim/pdf/OMIM_Graphics.pdf' target='_blank'>A quick reference overview and guide (PDF)</a>"></span>
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<div>
|
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<p />
|
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</div>
|
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|
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<div id="mimClinicalSynopsisFold" class="well well-sm collapse mimSingletonToggleFold">
|
|
<div class="small" style="margin: 5px">
|
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<div>
|
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<div>
|
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<span class="h5 mim-font">
|
|
<strong> INHERITANCE </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
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<div>
|
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<span class="mim-font">
|
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|
|
- Autosomal recessive <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/258211005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">258211005</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0441748&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0441748</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000007</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
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|
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</div>
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|
|
</div>
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> HEAD & NECK </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
|
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|
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<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Eyes </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Ptosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/11934000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">11934000</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/29696001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">29696001</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.409" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.409</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.40" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.40</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/H02.4" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H02.4</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/374.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">374.3</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/374.30" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">374.30</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0005745&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0005745</a>, <a href="https://bioportal.bioontology.org/search?q=C0033377&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0033377</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000508</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000508" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000508</a>]</span> <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=76abf29563d4adc64d21da86221224b1" target="_blank" class="small mim-tip-eom" title="<img src="https://elementsofmorphology.nih.gov/images/terms/Ptosis-small.jpg"> <br/>Further Information: <a href="https://elementsofmorphology.nih.gov/index.cgi?tid=76abf29563d4adc64d21da86221224b1" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'EOM\', \'domain\': \'elementsofmorphology.nih.gov\'})">Elements of Morphology</a>"><span class="glyphicon glyphicon-user" aria-hidden="true"></span></a><br /> -
|
|
Oculogyric crises <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/5332004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">5332004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0085637&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085637</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0010553" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0010553</a>]</span><br /> -
|
|
Miosis <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/415219007" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">415219007</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/63251006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">63251006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/301939004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">301939004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/H57.03" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">H57.03</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/379.42" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">379.42</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0026205&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0026205</a>, <a href="https://bioportal.bioontology.org/search?q=C0728710&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0728710</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000616" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000616</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000616" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000616</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Nose </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Nasal congestion <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/68235000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">68235000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R09.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R09.81</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0027424&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027424</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001742" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001742</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001742" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001742</a>]</span><br />
|
|
|
|
</span>
|
|
</div>
|
|
</div>
|
|
|
|
|
|
|
|
|
|
</div>
|
|
|
|
</div>
|
|
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<strong> CARDIOVASCULAR </strong>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
|
|
|
|
|
|
<div>
|
|
<div>
|
|
<span class="h5 mim-font">
|
|
<em> Vascular </em>
|
|
</span>
|
|
</div>
|
|
<div style="margin-left: 2em;">
|
|
<span class="mim-font">
|
|
|
|
- Hypotension <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/45007003" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">45007003</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/I95" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I95</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/I95.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">I95.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/458" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">458</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/458.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">458.9</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0020649&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0020649</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002615" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002615</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002615" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002615</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">
|
|
|
|
- Poor feeding <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>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/78164000" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">78164000</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R63.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R63.3</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>, <a href="https://bioportal.bioontology.org/search?q=C0232466&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0232466</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0011968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0011968</a>]</span><br /> -
|
|
Gastroesophageal reflux disease <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/235595009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">235595009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K21" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K21</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K21.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K21.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/530.81" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">530.81</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0017168&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0017168</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002020" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002020</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002020" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002020</a>]</span><br /> -
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Diarrhea <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/267060006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">267060006</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/62315008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">62315008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R19.7" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R19.7</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/787.91" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">787.91</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0011991&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0011991</a>, <a href="https://bioportal.bioontology.org/search?q=C2169706&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C2169706</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002014" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002014</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002014" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002014</a>]</span><br /> -
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Constipation <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/14760008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">14760008</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/K59.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K59.0</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/K59.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">K59.00</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/564.00" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">564.00</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/564.0" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">564.0</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0009806&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0009806</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002019" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002019</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002019" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002019</a>]</span><br />
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</span>
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</div>
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</div>
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</div>
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</div>
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<div>
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<div>
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<span class="h5 mim-font">
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<strong> NEUROLOGIC </strong>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<div>
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<div>
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<span class="h5 mim-font">
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<em> Central Nervous System </em>
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</span>
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</div>
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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Psychomotor delay <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/224958001" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">224958001</a>, <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">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/F88" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">F88</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0557874&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0557874</a>, <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> 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 /> -
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Developmental delay <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 /> -
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Truncal hypotonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1853743&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1853743</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008936" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008936</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0008936" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0008936</a>]</span><br /> -
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Impaired voluntary movement <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837621&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837621</a>]</span><br /> -
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Paroxysmal oculogyric crises <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837622&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837622</a>]</span><br /> -
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Limb dystonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0751093&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0751093</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002451" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002451</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002451" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002451</a>]</span><br /> -
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Limb hypertonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1838391&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1838391</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002509" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002509</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002509" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002509</a>]</span><br /> -
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Opisthotonic posturing <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837623&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837623</a>]</span><br /> -
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Orofacial dystonia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1395979&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1395979</a>]</span><br /> -
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Myoclonus <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/17450006" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">17450006</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G25.3" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G25.3</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/333.2" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">333.2</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0027066&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0027066</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001336" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001336</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001336" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001336</a>]</span><br /> -
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Hyperreflexia <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/86854008" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">86854008</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0151889&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0151889</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001347</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0001347" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0001347</a>]</span><br /> -
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|
Extensor plantar responses <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/246586009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">246586009</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/366575004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">366575004</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0034935&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0034935</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003487" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003487</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0003487" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0003487</a>]</span><br /> -
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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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Autonomic abnormalities <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837624&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837624</a>]</span><br /> -
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Sleep disturbances <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/39898005" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">39898005</a>, <a href="https://purl.bioontology.org/ontology/SNOMEDCT/53888004" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">53888004</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/G47" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G47</a>, <a href="https://purl.bioontology.org/ontology/ICD10CM/G47.9" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">G47.9</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/780.5" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">780.5</a>, <a href="https://purl.bioontology.org/ontology/ICD9CM/780.50" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">780.50</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0037317&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0037317</a>, <a href="https://bioportal.bioontology.org/search?q=C0851578&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0851578</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002360" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002360</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0002360" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0002360</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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Emotional lability <span class="mim-feature-ids hidden">[SNOMEDCT: <a href="https://purl.bioontology.org/ontology/SNOMEDCT/18963009" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'SNOMEDCT\', \'domain\': \'bioontology.org\'})">18963009</a>]</span> <span class="mim-feature-ids hidden">[ICD10CM: <a href="https://purl.bioontology.org/ontology/ICD10CM/R45.86" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD10CM\', \'domain\': \'bioontology.org\'})">R45.86</a>]</span> <span class="mim-feature-ids hidden">[ICD9CM: <a href="https://purl.bioontology.org/ontology/ICD9CM/799.24" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'ICD9CM\', \'domain\': \'bioontology.org\'})">799.24</a>]</span> <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0085633&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0085633</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000712" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000712</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0000712" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0000712</a>]</span><br />
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<strong> METABOLIC FEATURES </strong>
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<div style="margin-left: 2em;">
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- Paroxysmal sweating <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837638&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837638</a>]</span><br /> -
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Intermittent hypothermia <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837639&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837639</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005964" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005964</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005964" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005964</a>]</span><br /> -
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Temperature instability <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1820737&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1820737</a> HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005968</a>]</span> <span class="mim-feature-ids hidden">[HPO: <a href="https://hpo.jax.org/app/browse/term/HP:0005968" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'HPO\', \'domain\': \'hpo.jax.org\'})">HP:0005968</a>]</span><br />
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<strong> LABORATORY ABNORMALITIES </strong>
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<div style="margin-left: 2em;">
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- Decreased activity of aromatic L-amino acid decarboxylase (AADC) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837625&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837625</a>]</span><br /> -
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Decreased CSF homovanillic acid (HVA) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837626&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837626</a>]</span><br /> -
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Decreased CSF 5-hydroxyindoleacetic acid (5-HIAA) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837627&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837627</a>]</span><br /> -
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Decreased plasma catecholamines <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C0857654&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C0857654</a>]</span><br /> -
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Decreased whole blood serotonin <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837628&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837628</a>]</span><br /> -
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Increased CSF, plasma, and urinary L-dopa <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837629&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837629</a>]</span><br /> -
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Increased CSF, plasma, and urinary 5-hydroxytryptophan (5HTP) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837630&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837630</a>]</span><br /> -
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Increased CSF, plasma, and urinary 3-ortho-methyldopa (3-OMD) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837631&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837631</a>]</span><br /> -
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Increased CSF, plasma, and urinary 3-methoxytyrosine <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837632&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837632</a>]</span><br /> -
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Increased urinary dopamine and dopamine metabolites (paradoxical) <span class="mim-feature-ids hidden">[UMLS: <a href="https://bioportal.bioontology.org/search?q=C1837633&searchproperties=true" target="_blank" onclick="gtag(\'event\', \'mim_outbound\', {\'name\': \'UMLS\', \'domain\': \'bioontology.org\'})">C1837633</a>]</span><br />
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<span class="h5 mim-font">
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<strong> MISCELLANEOUS </strong>
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<div style="margin-left: 2em;">
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<div>
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<span class="mim-font">
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- Onset in early infancy<br /> -
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Drug-induced dyskinesias occur in a subset of patients<br /> -
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Diurnal fluctuation of symptoms<br />
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</span>
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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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<div style="margin-left: 2em;">
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<span class="mim-font">
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- Caused by mutation in the dopa decarboxylase gene (DDC, <a href="/entry/107930#0001">107930.0001</a>)<br />
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</span>
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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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<a id="text" class="mim-anchor"></a>
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<h4 href="#mimTextFold" id="mimTextToggle" class="mimTriangleToggle" style="cursor: pointer;" data-toggle="collapse">
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<span id="mimTextToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<span class="mim-tip-floating" qtip_title="<strong>Looking For More References?</strong>" qtip_text="Click the 'reference plus' icon <span class='glyphicon glyphicon-plus-sign'></span> at the end of each OMIM text paragraph to see more references related to the content of the preceding paragraph.">
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that aromatic L-amino acid decarboxylase deficiency (AADCD) is caused by homozygous or compound heterozygous mutation in the AADC gene (DDC; <a href="/entry/107930">107930</a>) on chromosome 7p12.</p>
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<a id="description" class="mim-anchor"></a>
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<span id="mimDescriptionToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<span class="mim-font">
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<strong>Description</strong>
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<p>Aromatic L-amino acid decarboxylase deficiency (AADCD) is an autosomal recessive inborn error in neurotransmitter metabolism that leads to combined serotonin and catecholamine deficiency (<a href="#1" class="mim-tip-reference" title="Abeling, N. G. G. M., Brautigam, C., Hoffmann, G. F., Barth, P. G., Wevers, R. A., Jaeken, J., Fiumara, A., Knust, A., van Gennip, A. H. <strong>Pathobiochemical implications of hyperdopaminuria in patients with aromatic L-amino acid decarboxylase deficiency.</strong> J. Inherit. Metab. Dis. 23: 325-328, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10896285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10896285</a>] [<a href="https://doi.org/10.1023/a:1005650325003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10896285">Abeling et al., 2000</a>). The disorder is clinically characterized by vegetative symptoms, oculogyric crises, dystonia, and severe neurologic dysfunction, usually beginning in infancy or childhood (summary by <a href="#5" class="mim-tip-reference" title="Brun, L., Ngu, L. H., Keng, W. T., Ch'ng, G. S., Choy, Y. S., Hwu, W. L., Lee, W. T., Willemsen, M. A. A. P., Verbeek, M. M., Wassenberg, T., Regal, L., Orcesi, S., and 13 others. <strong>Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency.</strong> Neurology 75: 64-71, 2010. Note: Erratum: Neurology 75: 576 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20505134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20505134</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181e620ae" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20505134">Brun et al., 2010</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10896285+20505134" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<a id="clinicalFeatures" class="mim-anchor"></a>
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<span id="mimClinicalFeaturesToggleTriangle" class="small mimTextToggleTriangle">▼</span>
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<strong>Clinical Features</strong>
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<p><a href="#11" class="mim-tip-reference" title="Hyland, K., Clayton, P. T. <strong>Aromatic amino acid decarboxylase deficiency in twins.</strong> J. Inherit. Metab. Dis. 13: 301-304, 1990.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1700191/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1700191</a>] [<a href="https://doi.org/10.1007/BF01799380" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1700191">Hyland and Clayton (1990)</a> and <a href="#12" class="mim-tip-reference" title="Hyland, K., Surtees, R. A. H., Rodeck, C., Clayton, P. T. <strong>Aromatic L-amino acid decarboxylase deficiency: clinical features, diagnosis, and treatment of a new inborn error of neurotransmitter amine synthesis.</strong> Neurology 42: 1980-1988, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1357595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1357595</a>] [<a href="https://doi.org/10.1212/wnl.42.10.1980" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1357595">Hyland et al. (1992)</a> reported male monozygotic twins born to first-cousin parents who presented at the age of 2 months with severe hypotonia and paroxysmal movements consisting of crying followed by extension of the arms and legs, oculogyric crises, and cyanosis. They also showed occasional choreoathetoid movements of the extremities. Later, defects in temperature regulation and postural hypotension were observed. Laboratory analyses showed a greatly decreased concentration of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the CSF, as well as decreased whole blood serotonin and plasma catecholamines. There was a significant elevation in the urinary excretion of L-DOPA, 5-hydroxytryptophan (5HTP), and 3-methoxytyrosine, all of which precede the AADC step in the biochemical pathway. The findings demonstrated that serotonin and dopamine synthesis were affected in both the central and peripheral nervous systems, consistent with a deficiency of AADC. AADC enzyme activity was severely reduced in plasma and in liver tissue (1% of control). Treatment with a monoamine oxidase inhibitor, a dopamine agonist, and pyridoxine resulted in a striking improvement in tone and movement. The parents were asymptomatic, but had biochemical profiles consistent with their being heterozygous for AADC deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1357595+1700191" 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="#16" class="mim-tip-reference" title="Maller, A., Hyland, K., Milstien, S., Biaggioni, I., Butler, I. J. <strong>Aromatic L-amino acid decarboxylase deficiency: clinical features, diagnosis, and treatment of a second family.</strong> J. Child Neurol. 12: 349-354, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9309516/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9309516</a>] [<a href="https://doi.org/10.1177/088307389701200602" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9309516">Maller et al. (1997)</a> reported an Iranian patient born of consanguineous parents who presented in infancy with hypotonia, paroxysmal episodes of inconsolable crying with eyes 'rolling backwards,' extension of extremities, and temperature instability. At age 5 years, he had severe developmental delay, profound hypotonia, and increased muscle tone in the extremities with brisk tendon reflexes and extensor plantar responses. Spontaneous movements were choreoathetoid, and he had increased sweating. CSF, blood, and urine analyses, as well as low AADC enzyme activity, were consistent with AADC deficiency. <a href="#14" class="mim-tip-reference" title="Korenke, G. C., Christen, H.-J., Hyland, K., Hunneman, D. H., Hanefeld, F. <strong>Aromatic L-amino acid decarboxylase deficiency: an extrapyramidal movement disorder with oculogyric crises.</strong> Europ. J. Paediat. Neurol. 1: 67-71, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10728198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10728198</a>]" pmid="10728198">Korenke et al. (1997)</a> reported a German patient with AADC born of unrelated parents. The clinical phenotype and laboratory findings were similar to previously reported cases. <a href="#14" class="mim-tip-reference" title="Korenke, G. C., Christen, H.-J., Hyland, K., Hunneman, D. H., Hanefeld, F. <strong>Aromatic L-amino acid decarboxylase deficiency: an extrapyramidal movement disorder with oculogyric crises.</strong> Europ. J. Paediat. Neurol. 1: 67-71, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10728198/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10728198</a>]" pmid="10728198">Korenke et al. (1997)</a> and <a href="#16" class="mim-tip-reference" title="Maller, A., Hyland, K., Milstien, S., Biaggioni, I., Butler, I. J. <strong>Aromatic L-amino acid decarboxylase deficiency: clinical features, diagnosis, and treatment of a second family.</strong> J. Child Neurol. 12: 349-354, 1997.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9309516/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9309516</a>] [<a href="https://doi.org/10.1177/088307389701200602" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9309516">Maller et al. (1997)</a> noted the clinical similarities between AADC deficiency and dihydropteridine reductase deficiency (<a href="/entry/261630">261630</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10728198+9309516" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#2" class="mim-tip-reference" title="Abeling, N. G. G. M., van Gennip, A. H., Barth, P. G., van Cruchten, A., Westra, M., Wijburg, F. A. <strong>Aromatic L-amino acid decarboxylase deficiency: a new case with a mild clinical presentation and unexpected laboratory findings.</strong> J. Inherit. Metab. Dis. 21: 240-242, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9686366/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9686366</a>] [<a href="https://doi.org/10.1023/a:1005307919767" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9686366">Abeling et al. (1998)</a> reported a Dutch girl with AADC deficiency who had a milder clinical phenotype, although she still exhibited psychomotor retardation and the characteristic hypertonic episodes with oculogyric crises. CSF showed decreased 5-HIAA and HVA, and urine showed decreased 5-HIAA, vanillylmandelic acid (VMA), and norepinephrine, elevated L-DOPA, but also elevated dopamine and HVA, which should have been decreased on the basis of the enzyme defect. Plasma AADC activity was undetectable. <a href="#2" class="mim-tip-reference" title="Abeling, N. G. G. M., van Gennip, A. H., Barth, P. G., van Cruchten, A., Westra, M., Wijburg, F. A. <strong>Aromatic L-amino acid decarboxylase deficiency: a new case with a mild clinical presentation and unexpected laboratory findings.</strong> J. Inherit. Metab. Dis. 21: 240-242, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9686366/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9686366</a>] [<a href="https://doi.org/10.1023/a:1005307919767" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9686366">Abeling et al. (1998)</a> suggested that the AADC deficiency was confined to the cerebral compartment. In examining several AADC patients, including the patient reported by <a href="#2" class="mim-tip-reference" title="Abeling, N. G. G. M., van Gennip, A. H., Barth, P. G., van Cruchten, A., Westra, M., Wijburg, F. A. <strong>Aromatic L-amino acid decarboxylase deficiency: a new case with a mild clinical presentation and unexpected laboratory findings.</strong> J. Inherit. Metab. Dis. 21: 240-242, 1998.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9686366/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9686366</a>] [<a href="https://doi.org/10.1023/a:1005307919767" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="9686366">Abeling et al. (1998)</a>, <a href="#1" class="mim-tip-reference" title="Abeling, N. G. G. M., Brautigam, C., Hoffmann, G. F., Barth, P. G., Wevers, R. A., Jaeken, J., Fiumara, A., Knust, A., van Gennip, A. H. <strong>Pathobiochemical implications of hyperdopaminuria in patients with aromatic L-amino acid decarboxylase deficiency.</strong> J. Inherit. Metab. Dis. 23: 325-328, 2000.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/10896285/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">10896285</a>] [<a href="https://doi.org/10.1023/a:1005650325003" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="10896285">Abeling et al. (2000)</a> found that all patients had hyperdopaminuria, which was increased after L-DOPA administration. HVA was also increased. The authors noted that dopamine is produced in the kidney by a renal form of AADC which is present in the proximal renal tubules and involved in the renal handling of sodium. In AADC-deficient patients, these renal cells receive increased amounts of the accumulated substrate L-DOPA, which is rapidly converted to dopamine and HVA. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=10896285+9686366" 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="Swoboda, K. J., Saul, J. P., McKenna, C. E., Speller, N. B., Hyland, K. <strong>Aromatic L-amino acid decarboxylase deficiency: overview of clinical features and outcomes.</strong> Ann. Neurol. 54: S49-S55, 2003.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/12891654/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">12891654</a>] [<a href="https://doi.org/10.1002/ana.10631" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="12891654">Swoboda et al. (2003)</a> reviewed the clinical phenotype of 11 patients with AADC deficiency, including 4 previously reported patients. Neonatal symptoms included poor feeding, lethargy, ptosis, hypothermia, and hypotension. All patients demonstrated intermittent eye movement abnormalities, truncal hypotonia, limb hypertonia, and impaired voluntary movements. The majority also showed emotional lability and irritability. Other features included myoclonus, dystonia, paroxysmal sweating, and gastrointestinal problems, such as reflux disease, constipation, and diarrhea. Functional clinical outcomes were poor. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=12891654" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#5" class="mim-tip-reference" title="Brun, L., Ngu, L. H., Keng, W. T., Ch'ng, G. S., Choy, Y. S., Hwu, W. L., Lee, W. T., Willemsen, M. A. A. P., Verbeek, M. M., Wassenberg, T., Regal, L., Orcesi, S., and 13 others. <strong>Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency.</strong> Neurology 75: 64-71, 2010. Note: Erratum: Neurology 75: 576 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20505134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20505134</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181e620ae" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20505134">Brun et al. (2010)</a> reviewed the clinical courses of 78 patients with AADC deficiency, including 32 patients who were reported for the first time. Most (96%) had symptoms evidence in infancy or childhood, including hypotonia (95%), oculogyric crises (86%), and developmental retardation (63%). The disorder became apparent during adolescence or adulthood in 6 patients. Other more variable features included autonomic symptoms, such as excessive sweating or temperature instability, feeding or speech difficulty, and movement disorders, including hypokinesia, dystonia, athetosis, and chorea. Many had insomnia and irritability, and 49 had motor or mental retardation. Laboratory data consistently showed low CSF levels of homovanillic acid, 5-hydroxyindoleacidic acid, and 3-methoxy-4-hydroxyphenolglycole, with increased 3-O-methyl-L-DOPA, L-DOPA, and 5-hydroxytryptophan. Urinary vanillactic acid was found in a few cases. Plasma AADC activity, when measured, was low or absent. About 24% of patients had an abnormal brain MRI, with cerebral atrophy, degenerative changes of the white matter, thinning of the corpus callosum, or a leukodystrophy-like pattern. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20505134" 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="#18" class="mim-tip-reference" title="Montioli, R., Battini, R., Paiardini, A., Tolve, M., Bertoldi, M., Carducci, C., Leuzzi, V., Voltattorni, C. B. <strong>A novel compound heterozygous genotype associated with aromatic amino acid decarboxylase deficiency: clinical aspects and biochemical studies.</strong> Molec. Genet. Metab. 127: 132-137, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31104889/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31104889</a>] [<a href="https://doi.org/10.1016/j.ymgme.2019.05.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31104889">Montioli et al. (2019)</a> reported a 5-year-old boy with a history of fluctuating eyelid ptosis since birth, early-onset hypotonia, fatigue, fluctuation of alertness, mild psychomotor delay, and language impairment. At 2 years of age, he developed oculogyric crises and dystonic upper limb movements. CSF analysis showed low homovanillic acid and 5-hydroxyindoleacetic acid and elevated 3-O-methyldopa and 5-HTP. Ptosis and oculogyric crises improved with levodopa/carbidopa, and fatigue and fluctuation of neurologic symptoms improved with transdermal rotigotine. At age 5 years, he had ptosis, episodic oculogyric crises without other movement abnormalities, mild global development delay, severe expressive language impairment, and behavioral abnormalities. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31104889" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p>The transmission pattern of AADCD in the family reported by <a href="#12" class="mim-tip-reference" title="Hyland, K., Surtees, R. A. H., Rodeck, C., Clayton, P. T. <strong>Aromatic L-amino acid decarboxylase deficiency: clinical features, diagnosis, and treatment of a new inborn error of neurotransmitter amine synthesis.</strong> Neurology 42: 1980-1988, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1357595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1357595</a>] [<a href="https://doi.org/10.1212/wnl.42.10.1980" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1357595">Hyland et al. (1992)</a> and <a href="#19" class="mim-tip-reference" title="Pons, R., Ford, B., Chiriboga, C. A., Clayton, P. T., Hinton, V., Hyland, K., Sharma, R., De Vivo, D. C. <strong>Aromatic L-amino acid decarboxylase deficiency: clinical features, treatment, and prognosis.</strong> Neurology 62: 1058-1065, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15079002/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15079002</a>] [<a href="https://doi.org/10.1212/wnl.62.7.1058" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15079002">Pons et al. (2004)</a> was consistent with autosomal recessive inheritance. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1357595+15079002" 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="#22" class="mim-tip-reference" title="Verbeek, M. M., Geurtz, P. B. H., Willemsen, M. A. A. P., Wevers, R. A. <strong>Aromatic L-amino acid decarboxylase enzyme activity in deficient patients and heterozygotes.</strong> Molec. Genet. Metab. 90: 363-369, 2007.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17240182/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17240182</a>] [<a href="https://doi.org/10.1016/j.ymgme.2006.12.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="17240182">Verbeek et al. (2007)</a> described assays for plasma AADC enzyme activity using both of its substrates, 5-hydroxytryptophan (5-HTP) and 3,4-dihydroxyphenylalanine (L-DOPA). They found that AADC enzyme activity in control plasma on average is a factor 8 to 12 higher with L-DOPA as substrate than with 5-HTP. Both substrates of AADC compete for the same active site of the enzyme resulting in equally decreased residual enzyme activities in AADC-deficient patients. In AADC-deficient patients, the enzyme activities towards both substrates are equally decreased, as are the CSF concentrations of HVA, 5-HIAA, and MHPG, whereas heterozygotes have intermediate AADC activity levels. These enzymes and assays can be performed on blood. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17240182" 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 clinical and molecular review of AADC deficiency, <a href="#9" class="mim-tip-reference" title="Himmelreich, N., Montioli, R., Bertoldi, M., Carducci, C., Leuzzi, V., Gemperle, C., Berner, T., Hyland, K., Thony, B., Hoffmann, G. F., Voltattorni, C. B., Blau, N. <strong>Aromatic amino acid decarboxylase deficiency: molecular and metabolic basis and therapeutic outlook.</strong> Molec. Genet. Metab. 127: 12-22, 2019. Note: Erratum: Molec. Genet. Metab. 134: 216 only, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30952622/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30952622</a>] [<a href="https://doi.org/10.1016/j.ymgme.2019.03.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30952622">Himmelreich et al. (2019)</a> stated that a diagnosis of AADC deficiency should be made based on positive findings in 2 of 3 diagnostic modalities: plasma AADC enzyme activity, molecular testing of the DDC gene, and/or CSF neurotransmitter metabolites. <a href="#9" class="mim-tip-reference" title="Himmelreich, N., Montioli, R., Bertoldi, M., Carducci, C., Leuzzi, V., Gemperle, C., Berner, T., Hyland, K., Thony, B., Hoffmann, G. F., Voltattorni, C. B., Blau, N. <strong>Aromatic amino acid decarboxylase deficiency: molecular and metabolic basis and therapeutic outlook.</strong> Molec. Genet. Metab. 127: 12-22, 2019. Note: Erratum: Molec. Genet. Metab. 134: 216 only, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30952622/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30952622</a>] [<a href="https://doi.org/10.1016/j.ymgme.2019.03.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30952622">Himmelreich et al. (2019)</a> noted that, if possible, all 3 tests should be performed, but that initiation of therapy should not be delayed if plasma and CSF studies are positive and molecular testing is pending. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30952622" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#4" class="mim-tip-reference" title="Brennenstuhl, H., Garbade, S. F., Okun, J. G., Feyh, P., Hoffmann, G. F., Langhans, C.-D., Opladen, T. <strong>Semi-quantitative detection of a vanillactic acid/vanillylmandelic acid ratio in urine is a reliable diagnostic marker for aromatic L-amino acid decarboxylase deficiency.</strong> Molec. Genet. Metab. 131: 163-170, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32675002/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32675002</a>] [<a href="https://doi.org/10.1016/j.ymgme.2020.07.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32675002">Brennenstuhl et al. (2020)</a> established a gas chromatography-mass spectrometry method to perform semiquantitative measurements of vanillactic acid (VLA) and vanillylmandelic acid (VMA) in urine, and tested the applicability of these measurements in the diagnosis of AADC deficiency. Testing in urine samples from 10,095 controls and 14 patients with AADC deficiency showed that VLA concentration correlated negatively with age, whereas VMA was stable with age. The mean VLA/VMA ratio was 0.07 (range, 0.0-23.24) in controls and 23.16 (range, 0.97-74.1) in patients. The VLA/VMA ratio was found to be age-dependent, and <a href="#4" class="mim-tip-reference" title="Brennenstuhl, H., Garbade, S. F., Okun, J. G., Feyh, P., Hoffmann, G. F., Langhans, C.-D., Opladen, T. <strong>Semi-quantitative detection of a vanillactic acid/vanillylmandelic acid ratio in urine is a reliable diagnostic marker for aromatic L-amino acid decarboxylase deficiency.</strong> Molec. Genet. Metab. 131: 163-170, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32675002/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32675002</a>] [<a href="https://doi.org/10.1016/j.ymgme.2020.07.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32675002">Brennenstuhl et al. (2020)</a> proposed age-related normal cut-off values in 3 age groups: a cut-off value of 8 for individuals between 0-1 years of age, a cut-off value of 6 for individuals between 1-10 years of age, and a cut-off value of 0.8 for individuals over 10 years of age. With these age-related normal values, the VLA/VMA ratio was highly sensitive for the diagnosis of AADC deficiency. Individually, VMA and VLA urinary concentrations were not sufficient to identify individuals with AADC deficiency. <a href="#4" class="mim-tip-reference" title="Brennenstuhl, H., Garbade, S. F., Okun, J. G., Feyh, P., Hoffmann, G. F., Langhans, C.-D., Opladen, T. <strong>Semi-quantitative detection of a vanillactic acid/vanillylmandelic acid ratio in urine is a reliable diagnostic marker for aromatic L-amino acid decarboxylase deficiency.</strong> Molec. Genet. Metab. 131: 163-170, 2020.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32675002/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32675002</a>] [<a href="https://doi.org/10.1016/j.ymgme.2020.07.001" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="32675002">Brennenstuhl et al. (2020)</a> concluded that the VLA/VMA ratio was a reliable parameter for the diagnosis of AADC deficiency. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32675002" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#6" class="mim-tip-reference" title="Burlina, A., Giuliani, A., Polo, G., Gueraldi, D., Gragnaniello, V., Cazzorla, C., Opladen, T., Hoffmann, G., Blau, N., Burlina, A. P. <strong>Detection of 3-O-methyldopa in dried blood spots for neonatal diagnosis of aromatic L-amino-acid decarboxylase deficiency: the northeastern Italian experience.</strong> Molec. Genet. Metab. 133: 56-62, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/33744095/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">33744095</a>] [<a href="https://doi.org/10.1016/j.ymgme.2021.03.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="33744095">Burlina et al. (2021)</a> developed a method for newborn screening for AADC deficiency by measurement of 3-O-methyldopa (3-OMD) in dried blood spots (DBS) using flow-injection analysis tandem mass-spectrometry with 13C-labeled tyrosine as an internal standard. The authors stated that because 13C-labeled tyrosine is already used as a standard reagent in newborn screening assays, this represents a simplification of prior proposed methodologies that use a deuterated 3-OMD as an internal standard. For those DBS measurements that fell above the established cutoff on this first-tier 3-OMD measurement, a second-tier test was used to measure 3-OMD by LC-MS/MS. The assay was shown to have a low coefficient of variation (less than 15%) and was validated in dried blood spots from 1,000 healthy newborns, 100 healthy control subjects, 81 patients receiving L-DOPA therapy, and a 25-year-old patient with AADC deficiency. Once validated, this assay was incorporated into an expanded newborn screening program in northeastern regions of Italy. No affected newborns were detected among 21,867 samples in the screening program; however, 1 infant had a false-positive result attributed to maternal L-DOPA therapy. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=33744095" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a prospective multicenter study at 3 centers in Germany, <a href="#20" class="mim-tip-reference" title="Reischl-Hajiabadi, A. T., Okun, J. G., Kohlmuller, D., Manukjan, G., Hegert, S., Durner, J., Schuhmann, E., Horster, F., Mutze, U., Feyh, P., Hoffmann, G. F., Roschinger, W., Janzen, N., Opladen, T. <strong>Newborn screening for aromatic l-amino acid decarboxylase deficiency--strategies, results, and implication for prevalence calculations.</strong> Molec. Genet. Metab. 141: 108148, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/38302374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">38302374</a>] [<a href="https://doi.org/10.1016/j.ymgme.2024.108148" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="38302374">Reischl-Hajiabadi et al. (2024)</a> evaluated newborn screening for elevated 3-O-methyldopa in bloodspots for the detection of AADC deficiency. Of a total of 766,660 newborns screened, 13 newborns had a positive screen. Of those with a positive screen, 1 infant was confirmed to have AADC deficiency, 1 infant was highly suspected to have AADC deficiency but died before a diagnosis could be confirmed, and 11 infants had false-positive results. The false-positive results were attributed to maternal L-dopa intake in 2 infants, to prematurity in 2 infants, and to unknown reasons in 7 infants. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=38302374" 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="#19" class="mim-tip-reference" title="Pons, R., Ford, B., Chiriboga, C. A., Clayton, P. T., Hinton, V., Hyland, K., Sharma, R., De Vivo, D. C. <strong>Aromatic L-amino acid decarboxylase deficiency: clinical features, treatment, and prognosis.</strong> Neurology 62: 1058-1065, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15079002/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15079002</a>] [<a href="https://doi.org/10.1212/wnl.62.7.1058" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15079002">Pons et al. (2004)</a> noted that clinical management of AADC deficiency usually involves vitamin B6, dopamine agonists, and MAO inhibitors to potentiate monoaminergic transmission. In assessing treatment response among a group of AADC patients, the authors detected 2 main groups: one with 5 males who responded to treatment and made developmental progress, and a second of 5 females and 1 male who responded poorly to treatment and often developed drug-induced dyskinesias. The findings suggested a sex difference in the monoaminergic system, with females being more dependent on the dopamine system. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=15079002" 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>Therapy is aimed at correcting the neurotransmitter abnormalities, especially those of serotonin and the catecholamines. Some may respond to L-DOPA. <a href="#5" class="mim-tip-reference" title="Brun, L., Ngu, L. H., Keng, W. T., Ch'ng, G. S., Choy, Y. S., Hwu, W. L., Lee, W. T., Willemsen, M. A. A. P., Verbeek, M. M., Wassenberg, T., Regal, L., Orcesi, S., and 13 others. <strong>Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency.</strong> Neurology 75: 64-71, 2010. Note: Erratum: Neurology 75: 576 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20505134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20505134</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181e620ae" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20505134">Brun et al. (2010)</a> reported 15 patients with a relatively mild form of the disorder who improved on a combined therapy with pyridoxine (B6)/pyridoxal phosphate, dopamine agonists, and monoamine oxidase B inhibitors. However, the authors remarked that drug treatment options are limited, in many cases not beneficial, and prognosis is uncertain. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20505134" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><strong><em>Gene Therapy</em></strong></p><p>
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<a href="#10" class="mim-tip-reference" title="Hwu, W.-L., Muramatsu, S., Tseng, S.-H., Tzen, K.-Y., Lee, N.-C., Chien, Y.-H., Snyder, R. O., Byrne, B. J., Tai, C.-H., Wu, R.-M. <strong>Gene therapy for aromatic L-amino acid decarboxylase deficiency.</strong> Sci. Transl. Med. 4: 134ra61, 2012. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22593174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22593174</a>] [<a href="https://doi.org/10.1126/scitranslmed.3003640" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22593174">Hwu et al. (2012)</a> performed AAV vector-mediated gene transfer of the human AADC gene (AAV2-hAADC) bilaterally into the putamen of 4 patients from Taiwan aged 4 to 6 years with AADC deficiency. All of the patients were bedridden, without head control and unable to talk. All of the patients showed improvements in motor performance. One patient was able to stand 16 months after gene transfer, and the other 3 patients achieved supported sitting 6 to 15 months after gene transfer. In all patients choreic dyskinesia occurred approximately 1 month after gene transfer; as dyskinesia resolved, motor development started. After 6 months, positron emission tomography (PET) in 3 patients revealed increased uptake of fluorodopa, a tracer for AADC, by the putamen. CSF analysis showed increased dopamine and serotonin levels after gene transfer. <a href="#10" class="mim-tip-reference" title="Hwu, W.-L., Muramatsu, S., Tseng, S.-H., Tzen, K.-Y., Lee, N.-C., Chien, Y.-H., Snyder, R. O., Byrne, B. J., Tai, C.-H., Wu, R.-M. <strong>Gene therapy for aromatic L-amino acid decarboxylase deficiency.</strong> Sci. Transl. Med. 4: 134ra61, 2012. Note: Electronic Article.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/22593174/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">22593174</a>] [<a href="https://doi.org/10.1126/scitranslmed.3003640" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="22593174">Hwu et al. (2012)</a> concluded that gene therapy targeting primary AADC deficiency is well tolerated and leads to improved motor function. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=22593174" 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>To establish the efficacy and safety of intraputaminal injection of AAV2-hAADC in patients with AADC deficiency, <a href="#8" class="mim-tip-reference" title="Chien, Y.-H., Lee, N.-C., Tseng, S.-H., Tai, C.-H., Muramatsu, S., Byrne, B. J., Hwu, W.-L. <strong>Efficacy and safety of AAV2 gene therapy in children with aromatic L-amino acid decarboxylase deficiency: an open-label, phase 1/2 trial.</strong> Lancet Child Adolesc. Health 1: 265-273, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30169182/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30169182</a>] [<a href="https://doi.org/10.1016/S2352-4642(17)30125-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30169182">Chien et al. (2017)</a> performed an open-label phase 1/2 trial of 10 patients (median age at surgery 2.71 years). <a href="#8" class="mim-tip-reference" title="Chien, Y.-H., Lee, N.-C., Tseng, S.-H., Tai, C.-H., Muramatsu, S., Byrne, B. J., Hwu, W.-L. <strong>Efficacy and safety of AAV2 gene therapy in children with aromatic L-amino acid decarboxylase deficiency: an open-label, phase 1/2 trial.</strong> Lancet Child Adolesc. Health 1: 265-273, 2017.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30169182/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30169182</a>] [<a href="https://doi.org/10.1016/S2352-4642(17)30125-6" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30169182">Chien et al. (2017)</a> assessed patients at baseline and at 3, 6, 9, and 12 months after gene therapy, and every 6 months thereafter for 1 further year. All patients tolerated the surgeries and vector injections. Primary efficacy outcomes were an increase in the Peabody Developmental Motor Scales (PDMS-2) score of greater than 10 points and an increase in homovanillic acid (HVA) or 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the cerebrospinal fluid 12 months after gene therapy. All patients met the primary efficacy endpoints: 12 months after gene therapy, PDMS-2 scores were increased by a median of 62 points, and HVA concentrations by a median of 25 nmol/L; however, there was no significant change in 5-HIAA concentrations. In total, 101 adverse events were reported, with the most common being pyrexia (16%) and orofacial dyskinesia (10%). Twelve serious adverse events occurred in 6 patients, including 1 death (treatment-unrelated encephalitis due to influenza B infection), 1 life-threatening pyrexia, and 10 events that led to hospital admission. Transient post-gene therapy dyskinesia occurred in all patients but was resolved with risperidone. Of 31 treatment-related adverse events, only one (patient 1) was severe in intensity, and none led to hospital admission or death. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30169182" 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="Kojima, K., Nakajima, T., Taga, N., Miyauchi, A., Kato, M., Matsumoto, A., Ikeda, T., Nakamura, K., Kubota, T., Mizukami, H., Ono, S., Onuki, Y., Sato, T., Osaka, H., Muramatsu, S., Yamagata, T. <strong>Gene therapy improves motor and mental function of aromatic L-amino acid decarboxylase deficiency.</strong> Brain 142: 322-333, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30689738/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30689738</a>, <a href="https://www.ncbi.nlm.nih.gov/pmc/?term=30689738[PMID]&report=imagesdocsum" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Image', 'domain': 'ncbi.nlm.nih.gov'})">images</a>] [<a href="https://doi.org/10.1093/brain/awy331" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30689738">Kojima et al. (2019)</a> conducted an open-label phase 1/2 study of older patients, including adolescents, with different degrees of severity. Six patients were enrolled: 4 males (ages 4, 10, 15, and 19 years) and 1 female (age 12 years) with a severe phenotype who were not capable of voluntary movement or speech, and 1 female (age 5 years) with a moderate phenotype who could walk with support. The patients were genetically diverse. At up to 2 years after gene therapy, the motor function was remarkably improved in all patients. Three patients with the severe phenotype were able to stand with support, and one patient could walk with a walker. The patient with the moderate phenotype could run and ride a bicycle, and also showed improvement in her mental function, being able to converse fluently and perform simple arithmetic. Dystonia disappeared and oculogyric crisis was markedly decreased in all patients. The patients exhibited transient choreic dyskinesia for several months, but no adverse events caused by vector were observed. PET showed increased uptake of fluoro-L-m-tyrosine (FMT) in the bilateral putamen. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30689738" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p>
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<p><a href="#3" class="mim-tip-reference" title="Blau, N. <strong>Estimating the prevalence of ultra-rare inherited metabolic disorders: Aromatic amino acid decarboxylase (AADC) deficiency.</strong> Molec. Genet. Metab. 141: 108150, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/38302375/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">38302375</a>] [<a href="https://doi.org/10.1016/j.ymgme.2024.108150" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="38302375">Blau (2024)</a> stated that birth rates for AADC deficiency are estimated to be 1:32,000 in Taiwan, 1:42,000 to 1:190,000 in the U.S., 1:116,000 in the European Union, and 1:162,000 in Japan. The disorder is thought to be more prevalent in certain Asian populations, particularly Taiwan, China, and Japan, due to the founder variant c.714+4A-T (<a href="/entry/107930#0007">107930.0007</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=38302375" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>Based on the findings of a newborn screening test for AADC in 766,660 infants in a prospective multicenter study in 3 centers in Germany, <a href="#20" class="mim-tip-reference" title="Reischl-Hajiabadi, A. T., Okun, J. G., Kohlmuller, D., Manukjan, G., Hegert, S., Durner, J., Schuhmann, E., Horster, F., Mutze, U., Feyh, P., Hoffmann, G. F., Roschinger, W., Janzen, N., Opladen, T. <strong>Newborn screening for aromatic l-amino acid decarboxylase deficiency--strategies, results, and implication for prevalence calculations.</strong> Molec. Genet. Metab. 141: 108148, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/38302374/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">38302374</a>] [<a href="https://doi.org/10.1016/j.ymgme.2024.108148" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="38302374">Reischl-Hajiabadi et al. (2024)</a> estimated the birth incidence of the disorder in this population to be between 1:766,600 and 1:383,330. <a href="#3" class="mim-tip-reference" title="Blau, N. <strong>Estimating the prevalence of ultra-rare inherited metabolic disorders: Aromatic amino acid decarboxylase (AADC) deficiency.</strong> Molec. Genet. Metab. 141: 108150, 2024.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/38302375/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">38302375</a>] [<a href="https://doi.org/10.1016/j.ymgme.2024.108150" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="38302375">Blau (2024)</a> noted that a prevalence of 1:766,600 was less common than initially expected. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=38302375+38302374" 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 6 patients with AADC deficiency, <a href="#7" class="mim-tip-reference" title="Chang, Y. T., Mues, G., McPherson, J. D., Bedell, J., Marsh, J. L., Hyland, K., Courtwright, K. H., Summers, J. W. <strong>Mutations in the human aromatic L-amino acid decarboxylase gene. (Abstract)</strong> J. Inherit. Metab. Dis. 21: 4 only, 1998."None>Chang et al. (1998)</a> identified 6 point mutations in the AADC gene (<a href="/entry/107930#0001">107930.0001</a>-<a href="/entry/107930#0006">107930.0006</a>). Four patients were homozygous, and 2 were compound heterozygous.</p><p>In monozygotic twin boys of Arab descent with AADC deficiency, who were first reported by <a href="#12" class="mim-tip-reference" title="Hyland, K., Surtees, R. A. H., Rodeck, C., Clayton, P. T. <strong>Aromatic L-amino acid decarboxylase deficiency: clinical features, diagnosis, and treatment of a new inborn error of neurotransmitter amine synthesis.</strong> Neurology 42: 1980-1988, 1992.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/1357595/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">1357595</a>] [<a href="https://doi.org/10.1212/wnl.42.10.1980" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="1357595">Hyland et al. (1992)</a>, <a href="#19" class="mim-tip-reference" title="Pons, R., Ford, B., Chiriboga, C. A., Clayton, P. T., Hinton, V., Hyland, K., Sharma, R., De Vivo, D. C. <strong>Aromatic L-amino acid decarboxylase deficiency: clinical features, treatment, and prognosis.</strong> Neurology 62: 1058-1065, 2004.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/15079002/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">15079002</a>] [<a href="https://doi.org/10.1212/wnl.62.7.1058" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="15079002">Pons et al. (2004)</a> identified homozygosity for a mutation in the AADC gene (<a href="/entry/107930#0002">107930.0002</a>). <a href="https://pubmed.ncbi.nlm.nih.gov/?term=1357595+15079002" 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>Among 49 patients with genetically confirmed AADC deficiency, <a href="#5" class="mim-tip-reference" title="Brun, L., Ngu, L. H., Keng, W. T., Ch'ng, G. S., Choy, Y. S., Hwu, W. L., Lee, W. T., Willemsen, M. A. A. P., Verbeek, M. M., Wassenberg, T., Regal, L., Orcesi, S., and 13 others. <strong>Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency.</strong> Neurology 75: 64-71, 2010. Note: Erratum: Neurology 75: 576 only, 2010.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20505134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20505134</a>] [<a href="https://doi.org/10.1212/WNL.0b013e3181e620ae" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="20505134">Brun et al. (2010)</a> reported 24 different mutations in the AADC gene, including 8 novel mutations. A splice site mutation (IVS6+4A-T; <a href="/entry/107930#0007">107930.0007</a>) was by far the most common mutation with an allele frequency of 45%. All patients with the IVS6+4A-T mutation were of Chinese or Taiwanese origin or lived in Taiwan. Other common mutations included S250F (<a href="/entry/107930#0002">107930.0002</a>), with an allele frequency of 10%, and G102S (<a href="/entry/107930#0001">107930.0001</a>), with an allele frequency of 8%. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20505134" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p>In a 5-year-old boy with AADC deficiency, <a href="#18" class="mim-tip-reference" title="Montioli, R., Battini, R., Paiardini, A., Tolve, M., Bertoldi, M., Carducci, C., Leuzzi, V., Voltattorni, C. B. <strong>A novel compound heterozygous genotype associated with aromatic amino acid decarboxylase deficiency: clinical aspects and biochemical studies.</strong> Molec. Genet. Metab. 127: 132-137, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31104889/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31104889</a>] [<a href="https://doi.org/10.1016/j.ymgme.2019.05.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31104889">Montioli et al. (2019)</a> identified compound heterozygous mutations in the AADC gene (A91V, <a href="/entry/107930#0005">107930.0005</a> and C410G, <a href="/entry/107930#0008">107930.0008</a>). <a href="#18" class="mim-tip-reference" title="Montioli, R., Battini, R., Paiardini, A., Tolve, M., Bertoldi, M., Carducci, C., Leuzzi, V., Voltattorni, C. B. <strong>A novel compound heterozygous genotype associated with aromatic amino acid decarboxylase deficiency: clinical aspects and biochemical studies.</strong> Molec. Genet. Metab. 127: 132-137, 2019.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/31104889/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">31104889</a>] [<a href="https://doi.org/10.1016/j.ymgme.2019.05.004" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="31104889">Montioli et al. (2019)</a> expressed A91V and C410G AADC homodimers in E. coli, and found that both showed decreased PLP binding affinity. In addition, an A91V/C410G heterodimer constructed via a dual-vector prokaryotic expression strategy showed decreased catalytic activity compared to the catalytic activity of either individual mutant homodimer, indicating a potential negative complementation effect. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=31104889" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})"><span class="glyphicon glyphicon-plus-sign mim-tip-hint" title="Click this 'reference-plus' icon to see articles related to this paragraph in PubMed."></span></a></p><p><a href="#9" class="mim-tip-reference" title="Himmelreich, N., Montioli, R., Bertoldi, M., Carducci, C., Leuzzi, V., Gemperle, C., Berner, T., Hyland, K., Thony, B., Hoffmann, G. F., Voltattorni, C. B., Blau, N. <strong>Aromatic amino acid decarboxylase deficiency: molecular and metabolic basis and therapeutic outlook.</strong> Molec. Genet. Metab. 127: 12-22, 2019. Note: Erratum: Molec. Genet. Metab. 134: 216 only, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/30952622/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">30952622</a>] [<a href="https://doi.org/10.1016/j.ymgme.2019.03.009" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="30952622">Himmelreich et al. (2019)</a> reviewed the 79 disease-causing mutations reported in the DDC locus-specific database (Pediatric Neurotransmitter Diseases database, PNDdb), which included 58 missense, 9 splice site, 6 frameshift, 1 in-frame, 3 complex, and 2 nonsense mutations. Fourteen mutations were predicted to affect the catalytic loop of the DDC protein, 4 were predicted to impair PLP binding, and 2 synonymous mutations were predicted to lead to abnormal splicing. <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=30952622" 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>Using an E. coli expression system, <a href="#15" class="mim-tip-reference" title="Longo, C., Montioli, R., Bisello, G., Palazzi, L., Mastrangelo, M., Brennenstuhl, H., Polverino de Laureto, P., Opladen, T., Leuzzi, V., Bertoldi, M. <strong>Compound heterozygosis in AADC deficiency: a complex phenotype dissected through comparison among heterodimeric and homodimeric AADC proteins.</strong> Molec. Genet. Metab. 134: 147-155, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34479793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34479793</a>] [<a href="https://doi.org/10.1016/j.ymgme.2021.08.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34479793">Longo et al. (2021)</a> examined the effects on enzyme structure and function of mutant AADC homodimers and heterodimers resulting from homozygous (T69M, S147R (107930.0004), M362T) or compound heterozygous (T69M/S147R; C281W/M362T) mutations in the DDC gene. The AADC T69M homodimer had about 11% catalytic efficiency and the AADC S147R homodimer had 0.001% catalytic efficiency. The AADC T69M/S147R heterodimer had 0.18% activity, despite being more stable than either homodimer, suggesting a negative complementation effect. The AADC C281W homodimer could not be assessed as a homodimer due to poor solubility, and the AADC M362T homodimer had 35% catalytic activity compared to wildtype. The C281W/M362T heterodimer was less stable than the M362T heterodimer but had 34% catalytic activity compared to wildtype. <a href="#15" class="mim-tip-reference" title="Longo, C., Montioli, R., Bisello, G., Palazzi, L., Mastrangelo, M., Brennenstuhl, H., Polverino de Laureto, P., Opladen, T., Leuzzi, V., Bertoldi, M. <strong>Compound heterozygosis in AADC deficiency: a complex phenotype dissected through comparison among heterodimeric and homodimeric AADC proteins.</strong> Molec. Genet. Metab. 134: 147-155, 2021.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/34479793/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">34479793</a>] [<a href="https://doi.org/10.1016/j.ymgme.2021.08.011" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="34479793">Longo et al. (2021)</a> concluded that if mutation in the DDC gene directly affects the AADC active site, it will cause more functional damage than does a mutation affecting protein folding. This may explain why a patient (patient 1, previously reported as patient 3 in <a href="#17" class="mim-tip-reference" title="Manegold, C., Hoffmann, G. F., Degen, I., Ikonomidou, H., Knust, A., Laass, M. W., Pritsch, M., Wilichowski, E., Horster, F. <strong>Aromatic L-amino acid decarboxylase deficiency: clinical features, drug therapy and follow-up.</strong> J. Inherit. Metab. Dis. 32: 371-380, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19172410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19172410</a>] [<a href="https://doi.org/10.1007/s10545-009-1076-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19172410">Manegold et al., 2009</a>) with AADC deficiency and a homozygous T69M mutation in the DDC gene had a milder phenotype compared to a patient (patient 2, previously reported as patient 6 in <a href="#17" class="mim-tip-reference" title="Manegold, C., Hoffmann, G. F., Degen, I., Ikonomidou, H., Knust, A., Laass, M. W., Pritsch, M., Wilichowski, E., Horster, F. <strong>Aromatic L-amino acid decarboxylase deficiency: clinical features, drug therapy and follow-up.</strong> J. Inherit. Metab. Dis. 32: 371-380, 2009.[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19172410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19172410</a>] [<a href="https://doi.org/10.1007/s10545-009-1076-1" target="_blank" onclick="gtag('event', 'mim_outbound', {'destination': 'Publisher'})">Full Text</a>]" pmid="19172410">Manegold et al., 2009</a>) with AADC deficiency and compound heterozygous mutations (T69M and S147R) in the DDC gene. <a href="https://pubmed.ncbi.nlm.nih.gov/?term=34479793+19172410" 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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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/9686366/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">9686366</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=9686366" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<strong>Estimating the prevalence of ultra-rare inherited metabolic disorders: Aromatic amino acid decarboxylase (AADC) deficiency.</strong>
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Molec. Genet. Metab. 141: 108150, 2024.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/38302375/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">38302375</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=38302375" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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<strong>Semi-quantitative detection of a vanillactic acid/vanillylmandelic acid ratio in urine is a reliable diagnostic marker for aromatic L-amino acid decarboxylase deficiency.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/32675002/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">32675002</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=32675002" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Brun, L., Ngu, L. H., Keng, W. T., Ch'ng, G. S., Choy, Y. S., Hwu, W. L., Lee, W. T., Willemsen, M. A. A. P., Verbeek, M. M., Wassenberg, T., Regal, L., Orcesi, S., and 13 others.
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<strong>Clinical and biochemical features of aromatic L-amino acid decarboxylase deficiency.</strong>
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Neurology 75: 64-71, 2010. Note: Erratum: Neurology 75: 576 only, 2010.
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/20505134/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">20505134</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=20505134" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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Burlina, A., Giuliani, A., Polo, G., Gueraldi, D., Gragnaniello, V., Cazzorla, C., Opladen, T., Hoffmann, G., Blau, N., Burlina, A. P.
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[<a href="https://doi.org/10.1016/j.ymgme.2021.03.009" target="_blank">Full Text</a>]
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Chang, Y. T., Mues, G., McPherson, J. D., Bedell, J., Marsh, J. L., Hyland, K., Courtwright, K. H., Summers, J. W.
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<strong>Mutations in the human aromatic L-amino acid decarboxylase gene. (Abstract)</strong>
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J. Inherit. Metab. Dis. 21: 4 only, 1998.
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<strong>Efficacy and safety of AAV2 gene therapy in children with aromatic L-amino acid decarboxylase deficiency: an open-label, phase 1/2 trial.</strong>
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[<a href="https://doi.org/10.1016/S2352-4642(17)30125-6" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2019.03.009" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1126/scitranslmed.3003640" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1007/BF01799380" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1212/wnl.42.10.1980" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1093/brain/awy331" target="_blank">Full Text</a>]
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Longo, C., Montioli, R., Bisello, G., Palazzi, L., Mastrangelo, M., Brennenstuhl, H., Polverino de Laureto, P., Opladen, T., Leuzzi, V., Bertoldi, M.
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[<a href="https://doi.org/10.1016/j.ymgme.2021.08.011" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1177/088307389701200602" target="_blank">Full Text</a>]
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/19172410/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">19172410</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=19172410" 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/10.1007/s10545-009-1076-1" target="_blank">Full Text</a>]
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<strong>A novel compound heterozygous genotype associated with aromatic amino acid decarboxylase deficiency: clinical aspects and biochemical studies.</strong>
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[<a href="https://doi.org/10.1016/j.ymgme.2019.05.004" target="_blank">Full Text</a>]
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[<a href="https://doi.org/10.1212/wnl.62.7.1058" target="_blank">Full Text</a>]
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Reischl-Hajiabadi, A. T., Okun, J. G., Kohlmuller, D., Manukjan, G., Hegert, S., Durner, J., Schuhmann, E., Horster, F., Mutze, U., Feyh, P., Hoffmann, G. F., Roschinger, W., Janzen, N., Opladen, T.
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[<a href="https://doi.org/10.1016/j.ymgme.2024.108148" target="_blank">Full Text</a>]
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<strong>Aromatic L-amino acid decarboxylase deficiency: overview of clinical features and outcomes.</strong>
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[<a href="https://doi.org/10.1002/ana.10631" target="_blank">Full Text</a>]
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<strong>Aromatic L-amino acid decarboxylase enzyme activity in deficient patients and heterozygotes.</strong>
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[PubMed: <a href="https://pubmed.ncbi.nlm.nih.gov/17240182/" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">17240182</a>, <a href="https://pubmed.ncbi.nlm.nih.gov/?cmd=link&linkname=pubmed_pubmed&from_uid=17240182" target="_blank" onclick="gtag('event', 'mim_outbound', {'name': 'PubMed Related', 'domain': 'pubmed.ncbi.nlm.nih.gov'})">related citations</a>]
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[<a href="https://doi.org/10.1016/j.ymgme.2006.12.001" target="_blank">Full Text</a>]
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 10/02/2024
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Hilary J. Vernon - updated : 08/10/2022<br>Hilary J. Vernon - updated : 06/03/2021<br>Hilary J. Vernon - updated : 05/28/2021<br>Hilary J. Vernon - updated : 04/06/2021<br>Hilary J. Vernon - updated : 09/01/2020<br>Ada Hamosh - updated : 12/03/2019<br>Cassandra L. Kniffin - updated : 6/20/2011<br>Ada Hamosh - updated : 6/14/2007<br>Cassandra L. Kniffin - updated : 8/27/2004
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Cassandra L. Kniffin : 5/7/2004
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carol : 10/02/2024
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alopez : 12/04/2023<br>alopez : 12/04/2023<br>carol : 08/11/2022<br>carol : 08/10/2022<br>carol : 11/08/2021<br>carol : 08/25/2021<br>carol : 06/24/2021<br>carol : 06/03/2021<br>carol : 05/28/2021<br>carol : 05/19/2021<br>carol : 04/07/2021<br>carol : 04/06/2021<br>carol : 09/01/2020<br>alopez : 12/03/2019<br>alopez : 12/03/2019<br>carol : 11/21/2014<br>mcolton : 2/24/2014<br>alopez : 7/12/2011<br>terry : 7/8/2011<br>wwang : 6/28/2011<br>ckniffin : 6/20/2011<br>alopez : 6/22/2007<br>terry : 6/14/2007<br>ckniffin : 8/27/2004<br>carol : 5/14/2004<br>ckniffin : 5/11/2004<br>ckniffin : 5/11/2004
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<span class="mim-font">
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<strong>#</strong> 608643
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AROMATIC L-AMINO ACID DECARBOXYLASE DEFICIENCY; AADCD
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<em>Alternative titles; symbols</em>
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AADC DEFICIENCY<br />
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DOPA DECARBOXYLASE DEFICIENCY<br />
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DDC DEFICIENCY
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<strong>SNOMEDCT:</strong> 124600004;
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<strong>ICD10CM:</strong> E70.81;
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<strong>ORPHA:</strong> 35708;
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<strong>DO:</strong> 0090123;
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<strong>Phenotype-Gene Relationships</strong>
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Location
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Phenotype
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Phenotype <br /> MIM number
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Inheritance
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Phenotype <br /> mapping key
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Gene/Locus <br /> MIM number
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<span class="mim-font">
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7p12.2-p12.1
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Aromatic L-amino acid decarboxylase deficiency
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608643
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Autosomal recessive
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<span class="mim-font">
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3
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DDC
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107930
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<strong>TEXT</strong>
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<p>A number sign (#) is used with this entry because of evidence that aromatic L-amino acid decarboxylase deficiency (AADCD) is caused by homozygous or compound heterozygous mutation in the AADC gene (DDC; 107930) on chromosome 7p12.</p>
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<strong>Description</strong>
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<p>Aromatic L-amino acid decarboxylase deficiency (AADCD) is an autosomal recessive inborn error in neurotransmitter metabolism that leads to combined serotonin and catecholamine deficiency (Abeling et al., 2000). The disorder is clinically characterized by vegetative symptoms, oculogyric crises, dystonia, and severe neurologic dysfunction, usually beginning in infancy or childhood (summary by Brun et al., 2010). </p>
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<strong>Clinical Features</strong>
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<p>Hyland and Clayton (1990) and Hyland et al. (1992) reported male monozygotic twins born to first-cousin parents who presented at the age of 2 months with severe hypotonia and paroxysmal movements consisting of crying followed by extension of the arms and legs, oculogyric crises, and cyanosis. They also showed occasional choreoathetoid movements of the extremities. Later, defects in temperature regulation and postural hypotension were observed. Laboratory analyses showed a greatly decreased concentration of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the CSF, as well as decreased whole blood serotonin and plasma catecholamines. There was a significant elevation in the urinary excretion of L-DOPA, 5-hydroxytryptophan (5HTP), and 3-methoxytyrosine, all of which precede the AADC step in the biochemical pathway. The findings demonstrated that serotonin and dopamine synthesis were affected in both the central and peripheral nervous systems, consistent with a deficiency of AADC. AADC enzyme activity was severely reduced in plasma and in liver tissue (1% of control). Treatment with a monoamine oxidase inhibitor, a dopamine agonist, and pyridoxine resulted in a striking improvement in tone and movement. The parents were asymptomatic, but had biochemical profiles consistent with their being heterozygous for AADC deficiency. </p><p>Maller et al. (1997) reported an Iranian patient born of consanguineous parents who presented in infancy with hypotonia, paroxysmal episodes of inconsolable crying with eyes 'rolling backwards,' extension of extremities, and temperature instability. At age 5 years, he had severe developmental delay, profound hypotonia, and increased muscle tone in the extremities with brisk tendon reflexes and extensor plantar responses. Spontaneous movements were choreoathetoid, and he had increased sweating. CSF, blood, and urine analyses, as well as low AADC enzyme activity, were consistent with AADC deficiency. Korenke et al. (1997) reported a German patient with AADC born of unrelated parents. The clinical phenotype and laboratory findings were similar to previously reported cases. Korenke et al. (1997) and Maller et al. (1997) noted the clinical similarities between AADC deficiency and dihydropteridine reductase deficiency (261630). </p><p>Abeling et al. (1998) reported a Dutch girl with AADC deficiency who had a milder clinical phenotype, although she still exhibited psychomotor retardation and the characteristic hypertonic episodes with oculogyric crises. CSF showed decreased 5-HIAA and HVA, and urine showed decreased 5-HIAA, vanillylmandelic acid (VMA), and norepinephrine, elevated L-DOPA, but also elevated dopamine and HVA, which should have been decreased on the basis of the enzyme defect. Plasma AADC activity was undetectable. Abeling et al. (1998) suggested that the AADC deficiency was confined to the cerebral compartment. In examining several AADC patients, including the patient reported by Abeling et al. (1998), Abeling et al. (2000) found that all patients had hyperdopaminuria, which was increased after L-DOPA administration. HVA was also increased. The authors noted that dopamine is produced in the kidney by a renal form of AADC which is present in the proximal renal tubules and involved in the renal handling of sodium. In AADC-deficient patients, these renal cells receive increased amounts of the accumulated substrate L-DOPA, which is rapidly converted to dopamine and HVA. </p><p>Swoboda et al. (2003) reviewed the clinical phenotype of 11 patients with AADC deficiency, including 4 previously reported patients. Neonatal symptoms included poor feeding, lethargy, ptosis, hypothermia, and hypotension. All patients demonstrated intermittent eye movement abnormalities, truncal hypotonia, limb hypertonia, and impaired voluntary movements. The majority also showed emotional lability and irritability. Other features included myoclonus, dystonia, paroxysmal sweating, and gastrointestinal problems, such as reflux disease, constipation, and diarrhea. Functional clinical outcomes were poor. </p><p>Brun et al. (2010) reviewed the clinical courses of 78 patients with AADC deficiency, including 32 patients who were reported for the first time. Most (96%) had symptoms evidence in infancy or childhood, including hypotonia (95%), oculogyric crises (86%), and developmental retardation (63%). The disorder became apparent during adolescence or adulthood in 6 patients. Other more variable features included autonomic symptoms, such as excessive sweating or temperature instability, feeding or speech difficulty, and movement disorders, including hypokinesia, dystonia, athetosis, and chorea. Many had insomnia and irritability, and 49 had motor or mental retardation. Laboratory data consistently showed low CSF levels of homovanillic acid, 5-hydroxyindoleacidic acid, and 3-methoxy-4-hydroxyphenolglycole, with increased 3-O-methyl-L-DOPA, L-DOPA, and 5-hydroxytryptophan. Urinary vanillactic acid was found in a few cases. Plasma AADC activity, when measured, was low or absent. About 24% of patients had an abnormal brain MRI, with cerebral atrophy, degenerative changes of the white matter, thinning of the corpus callosum, or a leukodystrophy-like pattern. </p><p>Montioli et al. (2019) reported a 5-year-old boy with a history of fluctuating eyelid ptosis since birth, early-onset hypotonia, fatigue, fluctuation of alertness, mild psychomotor delay, and language impairment. At 2 years of age, he developed oculogyric crises and dystonic upper limb movements. CSF analysis showed low homovanillic acid and 5-hydroxyindoleacetic acid and elevated 3-O-methyldopa and 5-HTP. Ptosis and oculogyric crises improved with levodopa/carbidopa, and fatigue and fluctuation of neurologic symptoms improved with transdermal rotigotine. At age 5 years, he had ptosis, episodic oculogyric crises without other movement abnormalities, mild global development delay, severe expressive language impairment, and behavioral abnormalities. </p>
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<span class="mim-font">
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<strong>Inheritance</strong>
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<p>The transmission pattern of AADCD in the family reported by Hyland et al. (1992) and Pons et al. (2004) was consistent with autosomal recessive inheritance. </p>
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<strong>Biochemical Features</strong>
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<p>Verbeek et al. (2007) described assays for plasma AADC enzyme activity using both of its substrates, 5-hydroxytryptophan (5-HTP) and 3,4-dihydroxyphenylalanine (L-DOPA). They found that AADC enzyme activity in control plasma on average is a factor 8 to 12 higher with L-DOPA as substrate than with 5-HTP. Both substrates of AADC compete for the same active site of the enzyme resulting in equally decreased residual enzyme activities in AADC-deficient patients. In AADC-deficient patients, the enzyme activities towards both substrates are equally decreased, as are the CSF concentrations of HVA, 5-HIAA, and MHPG, whereas heterozygotes have intermediate AADC activity levels. These enzymes and assays can be performed on blood. </p>
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<strong>Diagnosis</strong>
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<p>In a clinical and molecular review of AADC deficiency, Himmelreich et al. (2019) stated that a diagnosis of AADC deficiency should be made based on positive findings in 2 of 3 diagnostic modalities: plasma AADC enzyme activity, molecular testing of the DDC gene, and/or CSF neurotransmitter metabolites. Himmelreich et al. (2019) noted that, if possible, all 3 tests should be performed, but that initiation of therapy should not be delayed if plasma and CSF studies are positive and molecular testing is pending. </p><p>Brennenstuhl et al. (2020) established a gas chromatography-mass spectrometry method to perform semiquantitative measurements of vanillactic acid (VLA) and vanillylmandelic acid (VMA) in urine, and tested the applicability of these measurements in the diagnosis of AADC deficiency. Testing in urine samples from 10,095 controls and 14 patients with AADC deficiency showed that VLA concentration correlated negatively with age, whereas VMA was stable with age. The mean VLA/VMA ratio was 0.07 (range, 0.0-23.24) in controls and 23.16 (range, 0.97-74.1) in patients. The VLA/VMA ratio was found to be age-dependent, and Brennenstuhl et al. (2020) proposed age-related normal cut-off values in 3 age groups: a cut-off value of 8 for individuals between 0-1 years of age, a cut-off value of 6 for individuals between 1-10 years of age, and a cut-off value of 0.8 for individuals over 10 years of age. With these age-related normal values, the VLA/VMA ratio was highly sensitive for the diagnosis of AADC deficiency. Individually, VMA and VLA urinary concentrations were not sufficient to identify individuals with AADC deficiency. Brennenstuhl et al. (2020) concluded that the VLA/VMA ratio was a reliable parameter for the diagnosis of AADC deficiency. </p><p>Burlina et al. (2021) developed a method for newborn screening for AADC deficiency by measurement of 3-O-methyldopa (3-OMD) in dried blood spots (DBS) using flow-injection analysis tandem mass-spectrometry with 13C-labeled tyrosine as an internal standard. The authors stated that because 13C-labeled tyrosine is already used as a standard reagent in newborn screening assays, this represents a simplification of prior proposed methodologies that use a deuterated 3-OMD as an internal standard. For those DBS measurements that fell above the established cutoff on this first-tier 3-OMD measurement, a second-tier test was used to measure 3-OMD by LC-MS/MS. The assay was shown to have a low coefficient of variation (less than 15%) and was validated in dried blood spots from 1,000 healthy newborns, 100 healthy control subjects, 81 patients receiving L-DOPA therapy, and a 25-year-old patient with AADC deficiency. Once validated, this assay was incorporated into an expanded newborn screening program in northeastern regions of Italy. No affected newborns were detected among 21,867 samples in the screening program; however, 1 infant had a false-positive result attributed to maternal L-DOPA therapy. </p><p>In a prospective multicenter study at 3 centers in Germany, Reischl-Hajiabadi et al. (2024) evaluated newborn screening for elevated 3-O-methyldopa in bloodspots for the detection of AADC deficiency. Of a total of 766,660 newborns screened, 13 newborns had a positive screen. Of those with a positive screen, 1 infant was confirmed to have AADC deficiency, 1 infant was highly suspected to have AADC deficiency but died before a diagnosis could be confirmed, and 11 infants had false-positive results. The false-positive results were attributed to maternal L-dopa intake in 2 infants, to prematurity in 2 infants, and to unknown reasons in 7 infants. </p>
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<strong>Clinical Management</strong>
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<p><strong><em>Drug Therapy</em></strong></p><p>
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Pons et al. (2004) noted that clinical management of AADC deficiency usually involves vitamin B6, dopamine agonists, and MAO inhibitors to potentiate monoaminergic transmission. In assessing treatment response among a group of AADC patients, the authors detected 2 main groups: one with 5 males who responded to treatment and made developmental progress, and a second of 5 females and 1 male who responded poorly to treatment and often developed drug-induced dyskinesias. The findings suggested a sex difference in the monoaminergic system, with females being more dependent on the dopamine system. </p><p>Therapy is aimed at correcting the neurotransmitter abnormalities, especially those of serotonin and the catecholamines. Some may respond to L-DOPA. Brun et al. (2010) reported 15 patients with a relatively mild form of the disorder who improved on a combined therapy with pyridoxine (B6)/pyridoxal phosphate, dopamine agonists, and monoamine oxidase B inhibitors. However, the authors remarked that drug treatment options are limited, in many cases not beneficial, and prognosis is uncertain. </p><p><strong><em>Gene Therapy</em></strong></p><p>
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Hwu et al. (2012) performed AAV vector-mediated gene transfer of the human AADC gene (AAV2-hAADC) bilaterally into the putamen of 4 patients from Taiwan aged 4 to 6 years with AADC deficiency. All of the patients were bedridden, without head control and unable to talk. All of the patients showed improvements in motor performance. One patient was able to stand 16 months after gene transfer, and the other 3 patients achieved supported sitting 6 to 15 months after gene transfer. In all patients choreic dyskinesia occurred approximately 1 month after gene transfer; as dyskinesia resolved, motor development started. After 6 months, positron emission tomography (PET) in 3 patients revealed increased uptake of fluorodopa, a tracer for AADC, by the putamen. CSF analysis showed increased dopamine and serotonin levels after gene transfer. Hwu et al. (2012) concluded that gene therapy targeting primary AADC deficiency is well tolerated and leads to improved motor function. </p><p>To establish the efficacy and safety of intraputaminal injection of AAV2-hAADC in patients with AADC deficiency, Chien et al. (2017) performed an open-label phase 1/2 trial of 10 patients (median age at surgery 2.71 years). Chien et al. (2017) assessed patients at baseline and at 3, 6, 9, and 12 months after gene therapy, and every 6 months thereafter for 1 further year. All patients tolerated the surgeries and vector injections. Primary efficacy outcomes were an increase in the Peabody Developmental Motor Scales (PDMS-2) score of greater than 10 points and an increase in homovanillic acid (HVA) or 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the cerebrospinal fluid 12 months after gene therapy. All patients met the primary efficacy endpoints: 12 months after gene therapy, PDMS-2 scores were increased by a median of 62 points, and HVA concentrations by a median of 25 nmol/L; however, there was no significant change in 5-HIAA concentrations. In total, 101 adverse events were reported, with the most common being pyrexia (16%) and orofacial dyskinesia (10%). Twelve serious adverse events occurred in 6 patients, including 1 death (treatment-unrelated encephalitis due to influenza B infection), 1 life-threatening pyrexia, and 10 events that led to hospital admission. Transient post-gene therapy dyskinesia occurred in all patients but was resolved with risperidone. Of 31 treatment-related adverse events, only one (patient 1) was severe in intensity, and none led to hospital admission or death. </p><p>Kojima et al. (2019) conducted an open-label phase 1/2 study of older patients, including adolescents, with different degrees of severity. Six patients were enrolled: 4 males (ages 4, 10, 15, and 19 years) and 1 female (age 12 years) with a severe phenotype who were not capable of voluntary movement or speech, and 1 female (age 5 years) with a moderate phenotype who could walk with support. The patients were genetically diverse. At up to 2 years after gene therapy, the motor function was remarkably improved in all patients. Three patients with the severe phenotype were able to stand with support, and one patient could walk with a walker. The patient with the moderate phenotype could run and ride a bicycle, and also showed improvement in her mental function, being able to converse fluently and perform simple arithmetic. Dystonia disappeared and oculogyric crisis was markedly decreased in all patients. The patients exhibited transient choreic dyskinesia for several months, but no adverse events caused by vector were observed. PET showed increased uptake of fluoro-L-m-tyrosine (FMT) in the bilateral putamen. </p>
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<span class="mim-font">
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<strong>Population Genetics</strong>
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</span>
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</h4>
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<p>Blau (2024) stated that birth rates for AADC deficiency are estimated to be 1:32,000 in Taiwan, 1:42,000 to 1:190,000 in the U.S., 1:116,000 in the European Union, and 1:162,000 in Japan. The disorder is thought to be more prevalent in certain Asian populations, particularly Taiwan, China, and Japan, due to the founder variant c.714+4A-T (107930.0007). </p><p>Based on the findings of a newborn screening test for AADC in 766,660 infants in a prospective multicenter study in 3 centers in Germany, Reischl-Hajiabadi et al. (2024) estimated the birth incidence of the disorder in this population to be between 1:766,600 and 1:383,330. Blau (2024) noted that a prevalence of 1:766,600 was less common than initially expected. </p>
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<h4>
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<span class="mim-font">
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<strong>Molecular Genetics</strong>
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</span>
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</h4>
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<span class="mim-text-font">
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<p>In 6 patients with AADC deficiency, Chang et al. (1998) identified 6 point mutations in the AADC gene (107930.0001-107930.0006). Four patients were homozygous, and 2 were compound heterozygous.</p><p>In monozygotic twin boys of Arab descent with AADC deficiency, who were first reported by Hyland et al. (1992), Pons et al. (2004) identified homozygosity for a mutation in the AADC gene (107930.0002). </p><p>Among 49 patients with genetically confirmed AADC deficiency, Brun et al. (2010) reported 24 different mutations in the AADC gene, including 8 novel mutations. A splice site mutation (IVS6+4A-T; 107930.0007) was by far the most common mutation with an allele frequency of 45%. All patients with the IVS6+4A-T mutation were of Chinese or Taiwanese origin or lived in Taiwan. Other common mutations included S250F (107930.0002), with an allele frequency of 10%, and G102S (107930.0001), with an allele frequency of 8%. </p><p>In a 5-year-old boy with AADC deficiency, Montioli et al. (2019) identified compound heterozygous mutations in the AADC gene (A91V, 107930.0005 and C410G, 107930.0008). Montioli et al. (2019) expressed A91V and C410G AADC homodimers in E. coli, and found that both showed decreased PLP binding affinity. In addition, an A91V/C410G heterodimer constructed via a dual-vector prokaryotic expression strategy showed decreased catalytic activity compared to the catalytic activity of either individual mutant homodimer, indicating a potential negative complementation effect. </p><p>Himmelreich et al. (2019) reviewed the 79 disease-causing mutations reported in the DDC locus-specific database (Pediatric Neurotransmitter Diseases database, PNDdb), which included 58 missense, 9 splice site, 6 frameshift, 1 in-frame, 3 complex, and 2 nonsense mutations. Fourteen mutations were predicted to affect the catalytic loop of the DDC protein, 4 were predicted to impair PLP binding, and 2 synonymous mutations were predicted to lead to abnormal splicing. </p><p>Using an E. coli expression system, Longo et al. (2021) examined the effects on enzyme structure and function of mutant AADC homodimers and heterodimers resulting from homozygous (T69M, S147R (107930.0004), M362T) or compound heterozygous (T69M/S147R; C281W/M362T) mutations in the DDC gene. The AADC T69M homodimer had about 11% catalytic efficiency and the AADC S147R homodimer had 0.001% catalytic efficiency. The AADC T69M/S147R heterodimer had 0.18% activity, despite being more stable than either homodimer, suggesting a negative complementation effect. The AADC C281W homodimer could not be assessed as a homodimer due to poor solubility, and the AADC M362T homodimer had 35% catalytic activity compared to wildtype. The C281W/M362T heterodimer was less stable than the M362T heterodimer but had 34% catalytic activity compared to wildtype. Longo et al. (2021) concluded that if mutation in the DDC gene directly affects the AADC active site, it will cause more functional damage than does a mutation affecting protein folding. This may explain why a patient (patient 1, previously reported as patient 3 in Manegold et al., 2009) with AADC deficiency and a homozygous T69M mutation in the DDC gene had a milder phenotype compared to a patient (patient 2, previously reported as patient 6 in Manegold et al., 2009) with AADC deficiency and compound heterozygous mutations (T69M and S147R) in the DDC gene. </p>
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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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Burlina, A., Giuliani, A., Polo, G., Gueraldi, D., Gragnaniello, V., Cazzorla, C., Opladen, T., Hoffmann, G., Blau, N., Burlina, A. P.
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Chien, Y.-H., Lee, N.-C., Tseng, S.-H., Tai, C.-H., Muramatsu, S., Byrne, B. J., Hwu, W.-L.
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<strong>Efficacy and safety of AAV2 gene therapy in children with aromatic L-amino acid decarboxylase deficiency: an open-label, phase 1/2 trial.</strong>
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Himmelreich, N., Montioli, R., Bertoldi, M., Carducci, C., Leuzzi, V., Gemperle, C., Berner, T., Hyland, K., Thony, B., Hoffmann, G. F., Voltattorni, C. B., Blau, N.
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Hwu, W.-L., Muramatsu, S., Tseng, S.-H., Tzen, K.-Y., Lee, N.-C., Chien, Y.-H., Snyder, R. O., Byrne, B. J., Tai, C.-H., Wu, R.-M.
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Hyland, K., Surtees, R. A. H., Rodeck, C., Clayton, P. T.
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<strong>Aromatic L-amino acid decarboxylase deficiency: clinical features, diagnosis, and treatment of a new inborn error of neurotransmitter amine synthesis.</strong>
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Kojima, K., Nakajima, T., Taga, N., Miyauchi, A., Kato, M., Matsumoto, A., Ikeda, T., Nakamura, K., Kubota, T., Mizukami, H., Ono, S., Onuki, Y., Sato, T., Osaka, H., Muramatsu, S., Yamagata, T.
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<strong>Gene therapy improves motor and mental function of aromatic L-amino acid decarboxylase deficiency.</strong>
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Korenke, G. C., Christen, H.-J., Hyland, K., Hunneman, D. H., Hanefeld, F.
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<strong>Aromatic L-amino acid decarboxylase deficiency: an extrapyramidal movement disorder with oculogyric crises.</strong>
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Longo, C., Montioli, R., Bisello, G., Palazzi, L., Mastrangelo, M., Brennenstuhl, H., Polverino de Laureto, P., Opladen, T., Leuzzi, V., Bertoldi, M.
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<strong>Compound heterozygosis in AADC deficiency: a complex phenotype dissected through comparison among heterodimeric and homodimeric AADC proteins.</strong>
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Maller, A., Hyland, K., Milstien, S., Biaggioni, I., Butler, I. J.
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<li>
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<p class="mim-text-font">
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Manegold, C., Hoffmann, G. F., Degen, I., Ikonomidou, H., Knust, A., Laass, M. W., Pritsch, M., Wilichowski, E., Horster, F.
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<strong>Aromatic L-amino acid decarboxylase deficiency: clinical features, drug therapy and follow-up.</strong>
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[PubMed: 19172410]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Montioli, R., Battini, R., Paiardini, A., Tolve, M., Bertoldi, M., Carducci, C., Leuzzi, V., Voltattorni, C. B.
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<strong>A novel compound heterozygous genotype associated with aromatic amino acid decarboxylase deficiency: clinical aspects and biochemical studies.</strong>
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Molec. Genet. Metab. 127: 132-137, 2019.
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[PubMed: 31104889]
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[Full Text: https://doi.org/10.1016/j.ymgme.2019.05.004]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Pons, R., Ford, B., Chiriboga, C. A., Clayton, P. T., Hinton, V., Hyland, K., Sharma, R., De Vivo, D. C.
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<strong>Aromatic L-amino acid decarboxylase deficiency: clinical features, treatment, and prognosis.</strong>
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Neurology 62: 1058-1065, 2004.
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[PubMed: 15079002]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Reischl-Hajiabadi, A. T., Okun, J. G., Kohlmuller, D., Manukjan, G., Hegert, S., Durner, J., Schuhmann, E., Horster, F., Mutze, U., Feyh, P., Hoffmann, G. F., Roschinger, W., Janzen, N., Opladen, T.
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<strong>Newborn screening for aromatic l-amino acid decarboxylase deficiency--strategies, results, and implication for prevalence calculations.</strong>
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Molec. Genet. Metab. 141: 108148, 2024.
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[PubMed: 38302374]
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[Full Text: https://doi.org/10.1016/j.ymgme.2024.108148]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Swoboda, K. J., Saul, J. P., McKenna, C. E., Speller, N. B., Hyland, K.
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<strong>Aromatic L-amino acid decarboxylase deficiency: overview of clinical features and outcomes.</strong>
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Ann. Neurol. 54: S49-S55, 2003.
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[PubMed: 12891654]
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</p>
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</li>
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<li>
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<p class="mim-text-font">
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Verbeek, M. M., Geurtz, P. B. H., Willemsen, M. A. A. P., Wevers, R. A.
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<strong>Aromatic L-amino acid decarboxylase enzyme activity in deficient patients and heterozygotes.</strong>
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Molec. Genet. Metab. 90: 363-369, 2007.
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[PubMed: 17240182]
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[Full Text: https://doi.org/10.1016/j.ymgme.2006.12.001]
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</li>
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<div class="col-lg-1 col-md-1 col-sm-2 col-xs-2">
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<span class="text-nowrap mim-text-font">
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Contributors:
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</span>
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</div>
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<div class="col-lg-6 col-md-6 col-sm-6 col-xs-6">
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<span class="mim-text-font">
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Hilary J. Vernon - updated : 10/02/2024<br>Hilary J. Vernon - updated : 08/10/2022<br>Hilary J. Vernon - updated : 06/03/2021<br>Hilary J. Vernon - updated : 05/28/2021<br>Hilary J. Vernon - updated : 04/06/2021<br>Hilary J. Vernon - updated : 09/01/2020<br>Ada Hamosh - updated : 12/03/2019<br>Cassandra L. Kniffin - updated : 6/20/2011<br>Ada Hamosh - updated : 6/14/2007<br>Cassandra L. Kniffin - updated : 8/27/2004
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<span class="text-nowrap mim-text-font">
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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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Cassandra L. Kniffin : 5/7/2004
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carol : 10/02/2024<br>alopez : 12/04/2023<br>alopez : 12/04/2023<br>carol : 08/11/2022<br>carol : 08/10/2022<br>carol : 11/08/2021<br>carol : 08/25/2021<br>carol : 06/24/2021<br>carol : 06/03/2021<br>carol : 05/28/2021<br>carol : 05/19/2021<br>carol : 04/07/2021<br>carol : 04/06/2021<br>carol : 09/01/2020<br>alopez : 12/03/2019<br>alopez : 12/03/2019<br>carol : 11/21/2014<br>mcolton : 2/24/2014<br>alopez : 7/12/2011<br>terry : 7/8/2011<br>wwang : 6/28/2011<br>ckniffin : 6/20/2011<br>alopez : 6/22/2007<br>terry : 6/14/2007<br>ckniffin : 8/27/2004<br>carol : 5/14/2004<br>ckniffin : 5/11/2004<br>ckniffin : 5/11/2004
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