Urine Organic Acid (UOA) Analysis for the Diagnosis of Aromatic L-Amino Acid Decarboxylase (AADC) Deficiency

We describe the use of urine organic acid (UOA) analysis for the diagnosis of a CSF neurotransmitter defect, aromatic L-amino acid decarboxylase (AADC) deficiency in a 3-month-old boy. The patient presented with upper limbs spasm and abnormal eye movement. UOA was initiated for possible inborn errors of metabolism (IEM). Hyper-excretion of urine vanillactic acid (VLA) and N-acetyl-vanilalanine was detected in UOA which the pattern is pathognomonic to AADC deficiency. The diagnosis was subsequently confirmed by analysing the hotspot pathogenic variant in the DDC gene, i.e., IVS6+4A>T in <2 days. A CSF neurotransmitter profile was requested by the clinician and showed a classical pattern of AADC deficiency with markedly elevated 3-O-methyldopa of 2895 nmol/L (RI <300) and very low levels of 5-HIAA (<17 nmol/L; RI 114–335) and HVA (<67 nmol/L; RI 295–932). Because CSF sampling can be technically challenging and is also invasive, our case illustrates the potential of using non-invasive UOA to replace CSF neurotransmitter for the diagnosis of AADC. This is particularly useful clinically if sampling of CSF is practically infeasible. In conclusion, UOA is a simple and non-invasive test for AADC deficiency, and substantiate the previous work reported by Lee et al.1 Reference1.Lee HC, Lai CK, Yau KC, et al. Non-invasive urinary screening for aromatic L-amino acid decarboxylase deficiency in high-prevalence areas: a pilot study. Clin Chim Acta 2012; 413: 126–30.