A Comprehensive Meta-Analytical Investigation into the Incidence of Neonatal Amino Acid Metabolic Disorders Across China

Amino acid metabolic disorders (AAMs) are a group of inherited metabolic diseases caused by defects in enzymes or transporters involved in amino acid metabolism. This systematic review and meta-analysis aimed to evaluate the incidence, disease spectrum, and regional distribution of AAMs in China. A comprehensive search of PubMed, Embase, Web of Science, and major Chinese databases identified studies published between January 2002 and December 2025. After rigorous screening and quality assessment, 65 studies were included, encompassing 16,757,850 newborns and 2928 confirmed AAM cases. The most prevalent subtypes included hyperphenylalaninemia (HPA), hypermethioninemia (MET), citrin deficiency (CD), citrullinemia type 1 (CTLN1), maple syrup urine disease (MSUD), ornithine transcarbamylase deficiency (OTCD), and tyrosinemia (HT). The pooled incidence of AAMs was estimated at 184.0 (95% confidence interval 155.0–218.0) per million newborns. Significant regional differences were observed in the overall incidence of AAMs, with a higher incidence in northern China than southern China (287.0 vs. 126.0 per million, p < 0.0001). This difference was largely attributable to the substantially higher prevalence of HPA in northern China, whereas other major AAM subtypes showed no significant north–south differences. In contrast, no significant north–south differences were identified for other major subtypes. Additionally, the proportion of tetrahydrobiopterin deficiency (BH4D) among HPA cases was significantly higher in southern China (p < 0.001). These findings provide comprehensive epidemiological evidence on AAMs in China and highlight the importance of region-specific newborn screening strategies.