Organic acidurias, a subgroup of inborn errors of metabolism (IEMs), are characterized by the accumulation of non-amine-containing, low-molecular-weight organic acids (OAs) in urine and/or plasma due to defects in specific metabolic pathways. Early diagnosis can be critical to enable timely intervention to prevent irreversible neurological injury or death. Therefore, urine organic acid (UOA) testing plays an indispensable role in the differential diagnosis of symptomatic individuals and the follow-up of abnormal newborn screen results. Historically, gas chromatography-mass spectrometry (GC-MS) has been the gold standard method, with well-established protocols for sample preparation and result interpretation. Recent advances in liquid chromatography-mass spectrometry (LC-MS), including both triple quadrupole and high-resolution Quadrupole Time-of-Flight (QTOF) platforms, have enabled UOA analysis with simplified workflows and improved coverage to diagnose a broader array of IEMs. This review summarizes the evolution of UOA testing from manual colorimetric assays to mass spectrometry-based platforms, highlights the analytical and interpretative considerations of GC-MS, and explores emerging LC-MS technologies and bioinformatics tools that offer enhanced diagnostic capabilities and efficiency for the future of IEM testing.
Xiao et al. (2025) studied this question.