Background: Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive disorder of neurotransmitter synthesis. It has unique clinical presentations.
Aims: The purpose of this study is to delineate the clinical features and molecular spectrum of AADC deficiency in Taiwanese infants and children.
Methods: We report eight patients with characteristic clinical manifestations of AADC deficiency. Clinical presentations, treatment response, outcome and mutations of DOPA decarboxylase (DDC) gene were analyzed.
Results: The clinical manifestations were similar to those previously reported, including symptoms onset before age 1 year with features of severe floppiness, oculogyric crises, athetoid movement, prominent startle response, tongue thrusting, ptosis, paroxysmal diaphoresis, nasal congestion, diarrhea, irritability and sleep disorders. In addition, we observed that all patients (100.0%) had small hands and feet. During the period of follow-up, all of them (100.0%) presented severe floppiness in spite of therapeutic trials with vitamin B6, dopamine agonist, MAO inhibitor and/or anticholinergics. Three different mutations were identified in the DDC gene, including two novel mutations 1303 C>T and 1367ins A and one IVS 6+4 A>T mutation. The IVS 6+4 A>T was a splicing mutation, which inserted an additional 37nt of intron 6 into the DDC mRNA. Thirteen out of 16 alleles (81.3%) carried IVS 6+4 A>T mutation and the IVS 6+4 A>T alleles shared a conserved haplotype.
Conclusions: Patients with AADC deficiency in Taiwan have particular clinical manifestations of small hands and feet, which have rarely been mentioned in the literature. The prevalence of IVS 6+4 A>T splicing mutation is high in our study group and the IVS 6+4 A>T mutation might have a founder effect.