Objectives: Aromatic L aminoacid decarboxylase (AADC) deficiency is a rare disorder due to pathogenic variant of the dopa-decarboxylase (DCC) gene, resulting in decreased synthesis of dopamine and serotonin. Clinical spectrum include early-onset developmental delay, hypotonia, oculogyric crisis, dyautonomic features, mood and sleep disturbances We report the results of bilateral intraputaminal delivery of a gene vector expressing the DDC gene in two patients with AADC. 

Methods: 2 patients aged 10 and 11 received convective bilateral  intraputaminal injections of the viral vector (eladocagene exuparvovec, 1.8 x 10¹¹ vector genomes, infusion volume 2x80microlitres per putamen). Patients were assessed at base line, and prospectively after gene therapy with a follow-up of 15 months (patient 001) and 12 months (patient 002).

Results. Sleep disturbances, irritability and wakefulness improved by week 4. At last follow-up, both patients exhibited improvement of axial tonus, voluntary movements and motor function. Oral feeding was possible for the patient who was exclusively fed by a stomy before gene delivery. Brain imaging did not show any complication. Transient dyskinesias were noticed from week 5-6 after gene therapy. No serious adverse event has been reported.

Conclusion. Intraputaminal gene delivery in the 2 patients with AADC deficiency has been safe and well-tolerated, and resulted in significant improvement in motor and non-motor symptoms of the disease. Longer follow-up is necessary. Dedicated team for adequate perioperative management and specialized skills for close monitoring of gene therapy are recommended.