Comparison of Untargeted Metabolomic Profiling vs Traditional Metabolic Screening to Identify Inborn Errors of Metabolism

Key Points Question Is untargeted metabolomic profiling associated with a significant increase in the diagnostic rate of screening for inborn errors of metabolism (IEMs) compared with the traditional metabolic screening approach? Findings This cross-sectional analysis of 4464 traditional metabolic screening samples and 2000 plasma metabolomic screening samples received at a clinical biochemical laboratory between July 2014 and February 2019 found a 1.3% diagnostic rate for traditional metabolic screening, whereas clinical metabolomics supported diagnosis in 7.1% of cases, providing an approximately 6-fold higher diagnostic rate in screening for IEMs and identifying more disorders and more disease types compared with the traditional screening approach. Meaning With expanded newborn screening available in all states in the US, a broader approach to primary screening for IEMs is needed, and these data support the application of untargeted clinical metabolomics to serve as a primary screening approach.