Τίτλος:
AADC deficiency from infancy to adulthood: Symptoms and developmental outcome in an international cohort of 63 patients
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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
Συγγραφείς:
Pearson, T.S.
Gilbert, L.
Opladen, T.
Garcia-Cazorla, A.
Mastrangelo, M.
Leuzzi, V.
Tay, S.K.H.
Sykut-Cegielska, J.
Pons, R.
Mercimek-Andrews, S.
Kato, M.
Lücke, T.
Oppebøen, M.
Kurian, M.A.
Steel, D.
Manti, F.
Meeks, K.D.
Jeltsch, K.
Flint, L.
Περιοδικό:
Journal of Inherited Metabolic Disease
Εκδότης:
John Wiley and Sons Inc
Λέξεις-κλειδιά:
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
