Population-based newborn screening for inherited metabolic diseases in Beijing, China: findings from 404,990 infants

This study analyzed tandem mass spectrometry (MS/MS) screening results from 404,990 newborns in Beijing (2022-2025) to determine the incidence, outcomes, genetic findings, and follow-up of inherited metabolic diseases (IMDs).

Dried blood spot samples were screened by MS/MS for amino acid (AAs), organic acid (OAs), and fatty acid β-oxidation disorders (FAs). Positive cases were recalled for confirmatory and genetic testing.

A total of 243 cases of IMDs were diagnosed, including 123 cases of AAs (1:3293), 76 cases of OAs (1:5329), and 44 cases of FAs (1:9204). The regional specific incidence rate was 1:1667. PAH deficiency was the most prevalent AAs, with 99 cases (incidence 1:4091). MMA was the most common OAs, with 55 cases (incidence 1:7363). PCD was the predominant FAs, with 19 cases (incidence 1:21,315). In total, 22 types of IMDs were identified, including nine AAs, eight OAs, and five FAs. Genetic analysis identified hotspot variant s in PAH (c.728G>A [p.Arg243Gln] and c.158G>A [p.Arg53His]) and MMACHC (c.609G>A [p.Trp203*], c.482G>A [p.Arg161Gln], and c.658_660delAAG [p.Lys220del]). Three novel variants were identified. Of 243 confirmed patients, 236 received continuous treatment; 7 died.

This first large-scale MS/MS newborn screening in Beijing identified 22 IMDs types with a relatively high overall incidence. Three novel variants expand the variant spectrum. Early detection through MS/MS is critical for improving prognosis and represents a vital public health strategy. To further promote public health, future efforts will prioritize second-tier biochemical testing to improve PPV and diagnostic speed, and expand the panel only to clinically validated disorders. Genetic testing remains adjunctive for subtype confirmation; population-level application would require rigorous prospective evaluation.