A Mild Form of Aromatic L-amino Acid Decarboxylase Deficiency

Aromatic L-amino acid decarboxylase deficiency (AADCD) is a rare, autosomal recessive neurometabolic disorder that leads to a severe combined deficiency of serotonin, dopamine, norepinephrine and epinephrine. Most patients have early onset hypotonia, global developmental delay, dystonia, autonomic dysfunction, and oculogyric crisis (Wassenberg et al., 2017), thus presenting with a severe neurometabolic disorder with a poor prognosis. However, much less recognised and typical are the mild forms of AADC deficiency.

We present a clinical case of mild AADC deficiency and review his clinical presentation, molecular findings, and response to symptomatic therapy.

The 3-year-old boy has had hand tremors, progressive muscle weakness and oculogyric crisis since 6 months old and his symptoms were aggravated by fatigue and stress and more pronounced in the evenings. Two variants in the DDC gene were found: c.476CT, p.(Al159Val) – pathogenic, c.1337TC, p.(Leu446Pro) – likely pathogenic. AADC decarboxylase activity was low (6 nmol/min/l) and according to currently available guidelines, the diagnosis of AADC was confirmed. Since the start of therapy with pyridoxine and the dopamine agonist Bromcriptine, the boy started to crawl and walk, now he walks and runs independently, speech development is according to age, and the emergence of language has been observed sometimes in the evenings. Periodically, the boy had severe diarrhoea requiring the pyridoxine therapy to be stopped temporarily.

Analysing our experience so far, patients with a mild form of AADC deficiency have non-specific complaints. This disease may mask the diagnosis of cerebral palsy or epilepsy, as well as psychomotor delay and gastrointestinal diseases. Mild disease in our case had a good response to symptomatic therapy.