TY - JOUR
T1 - AADC deficiency from infancy to adulthood
T2 - Symptoms and developmental outcome in an international cohort of 63 patients
AU - Pearson, Toni S.
AU - Gilbert, Laura
AU - Opladen, Thomas
AU - Garcia-Cazorla, Angeles
AU - Mastrangelo, Mario
AU - Leuzzi, Vincenzo
AU - Tay, Stacy K.H.
AU - Sykut-Cegielska, Jolanta
AU - Pons, Roser
AU - Mercimek-Andrews, Saadet
AU - Kato, Mitsuhiro
AU - Lücke, Thomas
AU - Oppebøen, Mari
AU - Kurian, Manju A.
AU - Steel, Dora
AU - Manti, Filippo
AU - Meeks, Kathleen D.
AU - Jeltsch, Kathrin
AU - Flint, Lisa
N1 - Funding Information:
This study was supported by the Pediatric Neurotransmitter Disease Association and NIH/NINDS (5 R01-NS094292). AGC is funded by FIS: PI18/0111 (Instituto de Salud Carlos III: ISCIII and Fondo Europeo de desarrollo regional, FEDER).
Funding Information:
This study was supported by the Pediatric Neurotransmitter Disease Association and NIH/NINDS (5 R01‐NS094292). AGC is funded by FIS: PI18/0111 (Instituto de Salud Carlos III: ISCIII and Fondo Europeo de desarrollo regional, FEDER).
Funding Information:
Dr. Pearson reports that she is an investigator on a NIH‐funded gene therapy clinical trial for AADC deficiency. Dr. Opladen reports grants from Dietmar Hopp Foundation, during the conduct of the study. Dr. Garcia‐Cazorla reports personal fees from PTC Therapeutics, outside the submitted work. Dr. Kato reports grants from Nobelpharma Co., Ltd., outside the submitted work. Dr. Gilbert, Dr. Mastrangelo, Dr. Leuzzi, Dr. Tay, Dr. Sykut‐Cegielska, Dr. Pons, Dr. Mercimek‐Andrews, Dr. Lücke, Dr. Oppebøen, Dr. Kurian, Dr. Steel, Dr. Manti, Dr. Jeltsch, Ms. Black, and Ms. Flint declare that they have no conflict of interest.
Publisher Copyright:
© 2020 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM
PY - 2020/9/1
Y1 - 2020/9/1
N2 - 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.
AB - 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.
KW - dystonia-parkinsonism
KW - gene therapy
KW - natural history
KW - neurotransmitter disorders
KW - rare diseases
UR - http://www.scopus.com/inward/record.url?scp=85084612707&partnerID=8YFLogxK
U2 - 10.1002/jimd.12247
DO - 10.1002/jimd.12247
M3 - Article
C2 - 32369189
AN - SCOPUS:85084612707
VL - 43
SP - 1121
EP - 1130
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
SN - 0141-8955
IS - 5
ER -