Clinical and therapeutic observations in aromatic L-amino acid decarboxylase deficiency

Objectives: To elucidate the phenotype in aromatic L-amino acid decarboxyla se (AADC) deficiency, a rare autosomal recessive disorder of neurotransmitt er synthesis, and report preliminary treatment observations with directed t herapy of the associated neurotransmitter deficiencies. Background: AADC is a required enzyme in dopamine, norepinephrine, epinephrine, and serotonin biosynthesis. Five patients have been previously reported. Responses to tre atment interventions in these patients have been mixed. Methods: Clinical a nd biochemical evaluation and therapeutic trials were performed in two chil dren over a 26-month period. Results: Characteristic features included axia l hypotonia, hypokinesia, and athetosis, with superimposed episodes of ocul ar convergence spasm, oculogyric crises, dystonia, and limb rigidity. Catec holamine deficiency was manifest by ptosis, nasal congestion, paroxysmal di aphoresis, temperature instability, and blood pressure lability. Abnormal s leep, feeding difficulties, and esophageal reflux were typical. Significant therapeutic benefit was observed in one child with a combination of pergol ide, trihexyphenidyl, and tranylcypromine. Preliminary trials using seroton in receptor agonists or reuptake inhibitors resulted in adverse effects. Co nclusions: The movement disorder in AADC deficiency, particularly the chara cteristic eye movement abnormalities, should facilitate the identification of patients with this rare but possibly underrecognized disorder. Directed therapy of the underlying dopamine and norepinephrine deficiency may be ben eficial in some cases.