Clinical Domain Working Groups

Aromatic-L-amino acid decarboxylase (AADC) deficiency is an ultra-rare inherited autosomal recessive disorder characterized by sharply reduced synthesis of dopamine as well as other neurotransmitters. Symptoms, including hypotonia and movement disorders (especially oculogyric crisis and dystonia) as well as autonomic dysfunction and behavioral disorders, vary extensively and typically emerge in the first months of life. However, diagnosis is difficult, requiring analysis of metabolites in cerebrospinal fluid, assessment of plasma AADC activity, and/or DNA sequence analysis, and is frequently delayed for years. New metabolomics techniques promise early diagnosis of AADC deficiency by detection of 3-O-methyl-dopa in serum or dried blood spots.

In pursuit of providing high quality and systematic curation of DDC variants, we have assembled a panel of clinical, academic, and industry experts in the fields of genetics, pediatric neurology, functional genetics, and biochemistry. With research progressing and gene therapy emerging, determining the pathogenicity of variants is critical to ongoing efforts towards diagnosis and patient care. Curation efforts will synergize with ongoing functional studies, analyses of function/ genotype/phenotype correlations, and efforts to identify effective precision medications.