AADC deficiency from infancy to adulthood: Symptoms and developmental outcome in an international cohort of 63 patients.
J Inherit Metab Dis
; 43(5): 1121-1130, 2020 09.
Article
em En
| MEDLINE
| ID: mdl-32369189
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Descarboxilases de Aminoácido-L-Aromático
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Transtornos da Motilidade Ocular
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Agonistas de Dopamina
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Distúrbios Distônicos
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Erros Inatos do Metabolismo dos Aminoácidos
Tipo de estudo:
Diagnostic_studies
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Observational_studies
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Risk_factors_studies
Limite:
Adolescent
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Adult
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Child
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Child, preschool
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Female
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Humans
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Infant
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Male
Idioma:
En
Revista:
J Inherit Metab Dis
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos