Selective Serotonin Reuptake Inhibitor Treatment Post Gene Therapy for an Ultrarare Neurometabolic Disorder (AADC Deficiency)

Abstract

A 7-year-old girl presented with persistent anxiety symptoms for several years following gene therapy for an ultrarare neurometabolic disorder (aromatic L-amino acid decarboxylase [AADC] deficiency). AADC is the final enzyme in the monoamine synthesis pathway (Figure 1).¹ Its absence results in a severe combined deficiency in serotonin, dopamine, epinephrine, and norepinephrine, causing significant developmental delays, hypotonia, and dystonia. The incidence of AADC deficiency is estimated at ∼1 in 500,000,² and ∼200 cases have been described.¹ Recently available disease-modifying gene therapy for this condition dramatically improves motor symptoms, and received regulatory approval in some regions in 2022.² There are no data to guide psychiatric care post gene therapy for AADC or other neurologic disorders to date.³.