A Decade of Neonatal Inherited Metabolic Disorder Screening Experience in Ningbo, China: Screening Performance, Disease Spectrum, and Genetic Characteristics

Expanded newborn screening (NBS) using tandem mass spectrometry (MS/MS) can identify multiple inborn errors of metabolism (IEMs), but regional disease and genetic spectra vary. We retrospectively analyzed 611,080 newborns screened at the Women and Children’s Hospital of Ningbo University from July 2014 to December 2024. Amino acids and acylcarnitines were measured by MS/MS, and 256 newborns with persistently abnormal profiles underwent molecular testing using a 94-gene IEM panel or whole-exome sequencing. The initial screen-positive rate was 1.51% (9204), with a 98.9% recall success rate and a repeat positive rate of 11.0% (1003/9106). Integrated diagnostic assessment identified 137 confirmed IEM cases, giving a screen-detected IEM rate of 1 in 4460. Confirmed cases comprised 44 amino acid, 47 organic acid, and 46 fatty acid oxidation disorders. The three most frequent disorders were phenylketonuria, 3-methylcrotonyl-CoA carboxylase deficiency, and primary carnitine deficiency, with the predominant variants being PAH c.728G>A, MCCC1 c.1679dup, and SLC22A5 c.1400C>G. Additionally, 90 newborns with abnormal results on repeat MS/MS testing had single heterozygous findings, complicating diagnostic interpretation. These data characterize the screen-detected IEM spectrum and recurrent genetic variants in Ningbo and highlight the importance of integrating biochemical and molecular findings for gene- and variant-specific diagnostic interpretation.