Work

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

Year: 2026

Type: article

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.

Source: npj Genomic Medicine

DOI: 10.1038/s41525-026-00623-7