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The genetic and clinical characteristics of aromatic L-amino acid decarboxylase deficiency in mainland China

Abstract

Aromatic L-amino acid decarboxylase deficiency (AADCD) is a rare neurotransmitter metabolic disorder caused by DDC gene mutations, which leads to the metabolic disturbance of dopamine and serotonin. Most of the reported cases came from Taiwan China, but patients from mainland China were seldomly reported. The current study was the largest AADCD patient cohort from mainland China. Twenty-three patients with clinical features of AADCD and DDC gene variants were recruited. A total of 16 DDC variants were identified in this study, of which four variants (c.2T>C, c.277A>G, c.1021+1G>A, c.565G>T) were never reported previously. The intronic variant c.714+4A>T was the most common one, with an allele frequency of 45.7%. And patients carried this intronic variant presented with severe clinical manifestations, all of whom were bedridden. In this study, the average onset age was 3.61 ± 1.28 months and the average age of diagnosis was 12.91 ± 5.62 months. Early onset hypotonia, oculogyric crises, and autonomic symptoms such as excessive sweating, nasal congestion and profuse nasal, and oropharyngeal secretions, were common in our patients. Eighteen patients (78.3%) got various degree of improvement after using pyridoxine monotherapy or different combination of pyridoxine, dopamine agonists, and monoamine oxidase (MAO) inhibitors.

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Acknowledgements

We would like to thank the reported families for their cooperation in this study. Financial support has been provided by clinical research special fund of Wu Jieping Medical Foundation (grant No. 320.6750.17091, receiptor: Xinhua Bao), the Youth foundation of the National Natural Science Foundation of China (grant No. 81801128, receiptor: Qingping Zhang), and the Peking University First Hospital Scientific Research Seed Fund (grant No. 2018SF013, receiptor: Qingping Zhang).

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Correspondence to Xinhua Bao.

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Wen, Y., Wang, J., Zhang, Q. et al. The genetic and clinical characteristics of aromatic L-amino acid decarboxylase deficiency in mainland China. J Hum Genet 65, 759–769 (2020). https://doi.org/10.1038/s10038-020-0770-6

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