Exploring the technical possibilities of metabolomic versus genomic tests for diagnosis of inborn errors of metabolism in NICU

Abstract

Abstract Inborn errors of metabolism (IEMs) exhibit substantial biochemical and genetic heterogeneity and cause severe, life-threatening conditions in neonatal intensive care unit (NICU) newborns with high morbidity and mortality. Early diagnosis via high-throughput technology is crucial for optimizing neonatal IEM prognosis. To evaluate the feasibility of mass spectrometry and next-generation sequencing in IEM diagnosis, we retrospectively analyzed the diagnosis of IEMs from 1003 full-term newborns in NICU underwent metabolomic testing by tandem mass spectrometry‌ (MS/MS) and genomic sequencing by targeted next-generation sequencing (tNGS) on identical dried blood spots (DBS). The abnormal detection rates for metabolomic and genomic testing were 1.5% (15 out of 1003) and 15.6% (156 out of 1003) according to their respective reporting principles. Integrative analysis of MS, genetic sequencing and clinical features confirmed IEMs in seven patients, with suspected cases requiring long-term follow-up. Metabolomics enables rapid detection of metabolic abnormalities to guide immediate clinical management, while tNGS improves diagnostic accuracy and supports pre-symptomatic intervention in the NICU. Collectively, our study establishes an efficient dual-test diagnostic workflow for critically ill neonates, providing practical evidence for combined metabolomic and genomic IEM testing in future screening of large neonatal populations.

The authors' abstract, as published at the source. npj Genomic Medicine, 2026 · DOI ↗