A novel DDC gene deletion mutation in two Chinese mainland siblings with aromatic l-amino acid decarboxylase deficiency

Background Aromatic l -amino acid decarboxylase (AADC) deficiency (OMIM # 608643 ) is a rare and severe disorder of biogenic amine synthesis caused by mutations in the DDC gene. The phenomenology of the movement disorder includes intermittent oculogyric crises and limb dystonia, generalized athetosis, and impaired voluntary movement. Objective To identify clinical manifestations and DDC gene mutations in two Chinese mainland children who are siblings with AADC deficiency. Methods We used targeted next-generation sequencing and quantitative polymerase chain reaction (qPCR) to reveal DDC mutations in these children. Results Two DDC gene mutations were found: one missense mutation, c.1040G > A (p.Arg347Gln), is a reported mutation derived from the mother; the other mutation, a whole-exon 11 and 12 deletion, is a novel mutation derived from the father. The index patient and her brother both had poor sucking power and feeding difficulty at birth and episodes of oculogyric crises, truncal hypotonia, limb hypertonia, sleep disturbances, irritability, and motor delay. The siblings both died at 1 year and 10 months due to asphyxia and pneumonia during gaze and hypertonia episodes. Conclusion This study identified a novel DDC gene deletion mutation in two siblings with AADC deficiency disease in the Chinese mainland population.