AADC deficiency from infancy to adulthood: Symptoms and developmental outcome in an international cohort of 63 patients.
Aromatic l-amino acid decarboxylase deficiency (AADCD) is a rare, autosomal recessive neurodevelopmental disorder characterized by impaired synthesis of dopamine, noradrenaline, adrenaline and serotonin, leading to a complex syndrome of motor, behavioral, and autonomic symptoms. This retrospective study assessed the symptoms and developmental outcome of a large international cohort of patients with AADCD via physician and/or caregiver responses to a detailed, standardized questionnaire. Sixty-three patients (60% female; ages 6 months-36 years, median 7 years; 58 living) from 23 individual countries participated. Common symptoms at onset (median age 3 months, range 0-12 months) were hypotonia, developmental delay, and/or oculogyric crises. Oculogyric crises were present in 97% of patients aged 2 to 12 years, occurred in the majority of patients in all age groups, and tended to be most severe during early childhood. Prominent non-motor symptoms were sleep disturbance, irritable mood, and feeding difficulties. The majority of subjects (70%) had profound motor impairment characterized by absent head control and minimal voluntary movement, while 17% had mild motor impairment and were able to walk independently. Dopamine agonists were the medications most likely to produce some symptomatic benefit, but were associated with dose-limiting side effects (dyskinesia, insomnia, irritability, vomiting) that led to discontinuation 25% of the time. The age distribution of our cohort (70% of subjects under age 13 years) and the observation of a greater proportion of patients with a more severe disease phenotype in the younger compared to the older patients, both suggest a significant mortality risk during childhood for patients with severe disease.
['Pearson|Toni S|TS|0000-0002-3679-7707', 'Gilbert|Laura|L|', 'Opladen|Thomas|T|', 'Garcia-Cazorla|Angeles|A|', 'Mastrangelo|Mario|M|', 'Leuzzi|Vincenzo|V|', 'Tay|Stacy K H|SKH|', 'Sykut-Cegielska|Jolanta|J|', 'Pons|Roser|R|', 'Mercimek-Andrews|Saadet|S|', 'Kato|Mitsuhiro|M|', 'Lücke|Thomas|T|', 'Oppebøen|Mari|M|', 'Kurian|Manju A|MA|', 'Steel|Dora|D|', 'Manti|Filippo|F|', 'Meeks|Kathleen D|KD|', 'Jeltsch|Kathrin|K|', 'Flint|Lisa|L|']
D000293:Adolescent D000328:Adult D000367:Age Factors D000592:Amino Acid Metabolism, Inborn Errors D001142:Aromatic-L-Amino-Acid Decarboxylases D002648:Child D002675:Child, Preschool D018491:Dopamine Agonists D020821:Dystonic Disorders D005260:Female D015316:Genetic Therapy D006801:Humans D007223:Infant D038622:Internationality D008297:Male D015835:Ocular Motility Disorders D010641:Phenotype D012189:Retrospective Studies D055815:Young Adult
dystonia-parkinsonism gene therapy natural history neurotransmitter disorders rare diseases