@article{3077671,
    title = "AADC deficiency from infancy to adulthood: Symptoms and developmental outcome in an international cohort of 63 patients",
    author = "Pearson, T.S. and Gilbert, L. and Opladen, T. and Garcia-Cazorla, A. and Mastrangelo, M. and Leuzzi, V. and Tay, S.K.H. and Sykut-Cegielska, J. and Pons, R. and Mercimek-Andrews, S. and Kato, M. and Lücke, T. and Oppebøen, M. and Kurian, M.A. and Steel, D. and Manti, F. and Meeks, K.D. and Jeltsch, K. and Flint, L.",
    journal = "Journal of Inherited Metabolic Disease",
    year = "2020",
    volume = "43",
    number = "5",
    pages = "1121-1130",
    publisher = "John Wiley and Sons Inc",
    issn = "0141-8955",
    doi = "10.1002/jimd.12247",
    keywords = "bromocriptine;  pramipexole;  pyridoxine;  ropinirole;  rotigotine;  aromatic levo amino acid decarboxylase;  dopamine receptor stimulating agent, adolescent;  adult;  adulthood;  aromatic amino acid decarboxylase deficiency;  aromatic amino acid decarboxylase deficiency;  Article;  autosomal recessive disorder;  child;  clinical outcome;  cohort analysis;  developmental delay;  disease severity;  drug withdrawal;  dyskinesia;  feeding difficulty;  female;  human;  hyperhidrosis;  infancy;  infant;  insomnia;  irritability;  major clinical study;  male;  molecular genetics;  mortality risk;  motor dysfunction;  muscle hypotonia;  nose obstruction;  oculogyric crisis;  onset age;  phenotype;  preschool child;  questionnaire;  retrospective study;  school child;  side effect;  sleep disorder;  treatment response;  vomiting;  young adult;  age;  disorders of amino acid and protein metabolism;  dystonic disorder;  eye movement disorder;  gene therapy;  international cooperation;  pathophysiology, Adolescent;  Adult;  Age Factors;  Amino Acid Metabolism, Inborn Errors;  Aromatic-L-Amino-Acid Decarboxylases;  Child;  Child, Preschool;  Dopamine Agonists;  Dystonic Disorders;  Female;  Genetic Therapy;  Humans;  Infant;  Internationality;  Male;  Ocular Motility Disorders;  Phenotype;  Retrospective Studies;  Young Adult",
    abstract = "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. © 2020 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM"
}