Objective To investigate the clinical phenotypes and genetic characteristics of aromatic L-amino acid decarboxylase deficiency (AADCD). Methods A total of 10 children with AADCD who were admitted to the Department of Neurology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine from January 2020 to December 2024 were retrospectively enrolled. Their clinical data were collected and analyzed. Liquid chromatography-tandem mass spectrometry was used to determine the activity of peripheral blood aromatic L-amino acid decarboxylase (AADC), as well as the levels of cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA). High-throughput
sequencing was applied to detect pathogenic mutations of the DDC gene, and Sanger sequencing was used for site verification. Results Among the 10 children with AADCD, 6 cases were male and 4 cases were female. The onset age ranged from 1 to 8 months, and the median age at first visit was 4 years and 6 months (ranged from 8 months to 5 years and 10 months). One case had mild-to-moderate clinical phenotype, and 9 cases had severe phenotype. All patients presented with varying degrees of developmental delay, dystonia, frequent oculogyric crises and autonomic nervous system symptoms at onset. The levels of 5-HIAA and HVA in cerebrospinal fluid were significantly decreased, and the activity of AADC in peripheral blood was markedly reduced in 7 children. Genetic detection showed that 8 cases carried the c.714+4A>T (p.IVS6+4A>T) variant, including 3 cases of homozygous variant and 5 cases of compound heterozygous variant. The remaining 2 cases were compound heterozygous variants: c.478C>G (p.R160G) combined with c.565G>T (p.D189Y), and c.1021+1G>A (IVS10) combined with c.1234C>T (p.Arg412Trp), respectively. Conclusion AADCD is a rare condition that is prone to misdiagnosis and underdiagnosis. In children with unexplained motor and developmental delay accompanied by oculogyric crisis, this disease should be considered. The c.714+4A> T variant is the most common mutation site in Asian populations. All children in this study carrying either homozygous or heterozygous c.714+4A>T mutations exhibited severe phenotypes.
2026, Vol. 14 
