Newborn screening for inherited metabolic disorders in central China: a retrospective study of 153,956 infants using non-derivatized tandem mass spectrometry

Inherited metabolic disorders (IMDs) are genetic conditions characterized by toxic metabolite accumulation or deficiencies in essential products, often leading to severe clinical symptoms. Neonatal screening using advanced methods, such as tandem mass spectrometry (MS/MS), facilitates early detection and intervention, significantly expanding the range of detectable disorders. However, IMD incidence varies considerably across and within different regions globally. This study examined the incidence, spectrum, and genetic features of IMDs detectable by the regional MS/MS screening panel in a cohort of 153,956 newborns in Changzhi, central China, over the period from May 2015 to April 2020. MS/MS served as the primary screening tool, while GC/MS and next-generation sequencing (NGS) provided confirmatory analyses. Of the screened population, 129 infants received a diagnosis of IMDs, resulting in an incidence rate of 1 in 1,193 neonates. Confirmed cases comprised amino acid disorders (87 cases, 1:1,770), organic acidemias (23 cases, 1:6,694), and fatty acid oxidation disorders (18 cases, 1:8,553), with phenylalanine hydroxylase deficiency (PAHD) being the most prevalent disorder (64.4%, 1:1,855). Genetic analysis revealed particular mutations associated with specific IMDs. These findings provide region-specific epidemiological and genetic data on screened IMDs in central China, which may help inform future refinement of newborn screening panels and counselling strategies.