Neonatal World Conference 2026

Abstract

Newborn screening (NBS) is essential for the early identification of rare but treatable inborn errors of metabolism (IEMs), enabling timely intervention and improved clinical outcomes. Tandem mass spectrometry (MS/MS) is currently the cornerstone of expanded NBS programs due to its high throughput and capacity to simultaneously detect multiple metabolic disorders. More recently, next-generation sequencing (NGS) has emerged as a complementary tool, particularly valuable for confirmatory diagnosis and genetic characterization.

This study presents a comparative analysis of two national NBS programs: a large-scale cohort from Suzhou, China, and a pilot study from Slovenia. The Chinese program screened 401,660 newborns using MS/MS, identifying 153 confirmed IEM cases, with 138 individuals undergoing subsequent genetic analysis using NGS. The Slovenian study included 10,048 newborns, with 85 participants undergoing metabolic follow-up and 80 receiving NGS-based analysis. In both settings, MS/MS was used as the primary screening method, while NGS served as a second-line or confirmatory approach.

Results :

from both cohorts showed that amino acid metabolism disorders, particularly phenylketonuria (PKU), were the most frequently detected conditions, followed by fatty acid oxidation disorders such as primary carnitine deficiency (PCUD). Recurrent pathogenic variants in genes including PAH, SLC22A5, and MAT1A highlight the importance of molecular confirmation in improving diagnostic accuracy and guiding clinical management.

Overall, the integration of NGS with MS/MS significantly enhances diagnostic precision, reduces false-positive results, and supports early and accurate identification of IEMs. While MS/MS remains indispensable for large-scale population screening, NGS provides essential genetic resolution that strengthens confirmatory workflows and personalized care strategies.

Keywords :

Newborn screening, inborn errors of metabolism, tandem mass spectrometry, next-generation sequencing, phenylketonuria.