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

Toni S. Pearson, Laura Gilbert, Thomas Opladen, Angeles Garcia-Cazorla, Mario Mastrangelo, Vincenzo Leuzzi, Stacy K.H. Tay, Jolanta Sykut-Cegielska, Roser Pons, Saadet Mercimek-Andrews, Mitsuhiro Kato, Thomas Lücke, Mari Oppebøen, Manju A. Kurian, Dora Steel, Filippo Manti, Kathleen D. Meeks, Kathrin Jeltsch, Lisa Flint

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1121-1130
Number of pages10
JournalJournal of Inherited Metabolic Disease
Volume43
Issue number5
DOIs
StatePublished - Sep 1 2020

Keywords

  • dystonia-parkinsonism
  • gene therapy
  • natural history
  • neurotransmitter disorders
  • rare diseases

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