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Natural History of Aromatic L-Amino Acid Decarboxylase Deficiency in Taiwan.

ABSTRACT: OBJECTIVES:Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare inherited disorder of monoamine neurotransmitter synthesis; this deficiency leads to psychomotor delay, hypotonia, oculogyric crises, dystonia, and extraneurological symptoms. This study aimed to provide further insight into the clinical course of AADC deficiency in Taiwan. PATIENTS AND METHODS:We present a retrospective, descriptive, single-center study of 37 children with a confirmed diagnosis of AADC deficiency. Their medical histories were reviewed for motor milestones, motor development, DDC mutation, and body weight. The termination point for each patient in this study was defined as no further follow-up, death, or enrollment in a gene therapy trial. RESULTS:The median age of the study patients at the end of the study was 4.39 years (1.28-11.30). Of the 37 patients, 36 did not develop full head control, sitting ability, standing ability, or speech at any time point from birth to the termination points. Motor scales were administered to 22 patients. Their Alberta Infant Motor Scale scores were below the fifth percentile, and their Peabody Developmental Motor Scales, Second Edition, scores were below the first percentile. Their body weights were normal in the first few months of life, but severe growth retardation occurred at later ages. The mutation c.714+4A>T (IVS6+4A>T) accounted for 76% of all their DDC mutations. CONCLUSION:In this chapter, we report the clinical course of AADC deficiency in Taiwan. Our data will help guide the development of treatment strategies for the disease.

SUBMITTER: Hwu WL

PROVIDER: S-EPMC6122029 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Natural History of Aromatic L-Amino Acid Decarboxylase Deficiency in Taiwan.

Hwu Wuh-Liang WL Chien Yin-Hsiu YH Lee Ni-Chung NC Li Mei-Hsin MH

JIMD reports 20170831

<h4>Objectives</h4>Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare inherited disorder of monoamine neurotransmitter synthesis; this deficiency leads to psychomotor delay, hypotonia, oculogyric crises, dystonia, and extraneurological symptoms. This study aimed to provide further insight into the clinical course of AADC deficiency in Taiwan.<h4>Patients and methods</h4>We present a retrospective, descriptive, single-center study of 37 children with a confirmed diagnosis of AADC def ...[more]

PMID: 28856607

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Project description:In patients with aromatic l-amino acid decarboxylase (AADC) deficiency, a decrease in catecholamines and serotonin levels in the brain leads to developmental delay and movement disorders. The beneficial effects of gene therapy in patients from 1 to 8 years of age with homogeneous severity of disease have been reported from Taiwan. We conducted an open-label phase 1/2 study of population including adolescent patients with different degrees of severity. Six patients were enrolled: four males (ages 4, 10, 15 and 19 years) and one female (age 12 years) with a severe phenotype who were not capable of voluntary movement or speech, and one female (age 5 years) with a moderate phenotype who could walk with support. The patients received a total of 2 × 1011 vector genomes of adeno-associated virus vector harbouring DDC via bilateral intraputaminal infusions. At up to 2 years after gene therapy, the motor function was remarkably improved in all patients. Three patients with the severe phenotype were able to stand with support, and one patient could walk with a walker, while the patient with the moderate phenotype could run and ride a bicycle. This moderate-phenotype patient also showed improvement in her mental function, being able to converse fluently and perform simple arithmetic. Dystonia disappeared and oculogyric crisis was markedly decreased in all patients. The patients exhibited transient choreic dyskinesia for a couple of months, but no adverse events caused by vector were observed. PET with 6-[18F]fluoro-l-m-tyrosine, a specific tracer for AADC, showed a persistently increased uptake in the broad areas of the putamen. In our study, older patients (>8 years of age) also showed improvement, although treatment was more effective in younger patients. The genetic background of our patients was heterogeneous, and some patients suspected of having remnant enzyme activity showed better improvement than the Taiwanese patients. In addition to the alleviation of motor symptoms, the cognitive and verbal functions were improved in a patient with the moderate phenotype. The restoration of dopamine synthesis in the putamen via gene transfer provides transformative medical benefit across all patient ages, genotypes, and disease severities included in this study, with the most pronounced improvements noted in moderate patients.10.1093/brain/awy331_video1awy331media15991361892001.

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Natural History of Aromatic L-Amino Acid Decarboxylase Deficiency in Taiwan.

Publications

Natural History of Aromatic L-Amino Acid Decarboxylase Deficiency in Taiwan.

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