AADC deficiency from infancy to adulthood: Symptoms and developmental outcome in an international cohort of 63 patients

J Inherit Metab Dis. 2020 Sep;43(5):1121-1130. doi: 10.1002/jimd.12247. Epub 2020 May 14.


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.

Keywords: dystonia-parkinsonism; gene therapy; natural history; neurotransmitter disorders; rare diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Amino Acid Metabolism, Inborn Errors / physiopathology*
  • Amino Acid Metabolism, Inborn Errors / therapy*
  • Aromatic-L-Amino-Acid Decarboxylases / deficiency*
  • Child
  • Child, Preschool
  • Dopamine Agonists / adverse effects
  • Dopamine Agonists / therapeutic use*
  • Dystonic Disorders / etiology*
  • Female
  • Genetic Therapy
  • Humans
  • Infant
  • Internationality
  • Male
  • Ocular Motility Disorders / etiology*
  • Phenotype
  • Retrospective Studies
  • Young Adult


  • Dopamine Agonists
  • Aromatic-L-Amino-Acid Decarboxylases

Supplementary concepts

  • Aromatic amino acid decarboxylase deficiency