Aromatic amino acid decarboxylase deficiency: Molecular and metabolic basis and therapeutic outlook

Publication date: Available online 27 March 2019Source: Molecular Genetics and MetabolismAuthor(s): Nastassja Himmelreich, Riccardo Montioli, Mariarita Bertoldi, Carla Carducci, Vincenzo Leuzzi, Corinne Gemperle, Todd Berner, Keith Hyland, Beat Thöny, Georg F. Hoffmann, Carla B. Voltattorni, Nenad BlauAbstractAromatic-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. A total of 82 dopa decarboxylase (DDC) variants in the DDC gene leading to AADC deficiency have been identified and catalogued for all known patients (n = 119). Biochemical and bioinformatics studies provided insight into the impact of many variants. c.714 + 4A > T, p.S250F, p.R347Q, and p.G102S are the most frequent variants (cumulative allele frequency = 57%), and c.[714 + 4A > T];[714 + 4A > T], p....
Source: Molecular Genetics and Metabolism - Category: Genetics & Stem Cells Source Type: research