Determination of 3-O-methyldopa levels in dried blood spots of patients with associated pathologies to AADC deficiency from Gran Canaria Island

Abstract Introduction Aromatic L-amino acid decarboxylase deficiency (AADC) is likely underdiagnosed due to its non-specific signs and broad phenotypic spectrum. Its diagnosis requires analysis of neurotransmitter metabolites in cerebrospinal fluid, AADC enzyme activity, or genetic study of the DDC gene. Affected patients with very early and severe clinical manifestations have very high levels of 3-O-methyldopa (3-OMD). However, the normal ranges and exact cut-off levels of 3-OMD are not well-defined in the general population or among patients with a mild clinical phenotype. Objective To evaluate 3-OMD levels in dried blood spots and other characteristics in various subgroups of patients with clinical signs compatible with AADC deficiency, residents in Gran Canaria (Canary Islands, Spain). Methods 3-OMD values in dried blood spots (DBS) were retrospectively analysed in 358 patients. Patients were classified into four subgroups, according to the clinical presentation (epilepsy, oculogyric crisis, autism spectrum disorder [ASD], and hypotonia), and were compared by age, sex, municipality, and rehabilitation attendance. The variation of 3-OMD levels was examined with linear models. Results Median 3-OMD concentration was 113 nmol/L (range 34.1 nmol/L to 339.0 nmol/L). Age correlated negatively with the biomarker 3-OMD in the overall patient population and the epilepsy and ASD subgroups. The different subgroups presented different biomarker profiles. Conclusions 3-OMD levels in DBS were negatively associated with age. This fact should be considered when using the marker to diagnose AADC deficiency in cases of mild phenotype and late onset after birth. The 3-OMD concentrations suggested no patients with AADC deficiency in our study population, which was confirmed genetically.