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.

Keywords: Aromatic L-amino acid decarboxylase; Body weight; Development; Natural history; Neurotransmitter; Taiwan.

Fig. 1

Body weight of 37 patients with AADC deficiency. Body weight at each visit was plotted according to age, in comparison with the body weight distribution of normal Taiwanese female children (Chen and Chang 2010). Each line represents one patient. One outlier (patient No. 37), who had significantly greater growth than other patients, is indicated by the red arrow

Fig. 2

AIMS scores of 22 patients with AADC deficiency. Data from patients (blue diamond) are depicted according to the age at the time of measurement. The red diamonds indicate the fifth percentile and the green diamonds indicate the 50th percentile of normal children (Darrah et al. 2014)