Comparative analysis of inherited metabolic diseases in normal newborns and high-risk children: Insights from a 10-year study in Shanghai

Compare the differences between normal newborns and high-risk children with inherited metabolic diseases. The disease profile includes amino acidemias, fatty acid oxidation disorders, and organic acidemias. Data was collected on newborns and children from high-risk populations in Shanghai from December 2010 to December 2020. 232,561 newborns were screened for disorders of organic, amino acid, and fatty acid metabolism. The initial positive rate was 0.66 % (1,526/232,561) and the positive recall rate was 77.85 %. The positive predictive value is 4.71 %. Among them, 56 cases were diagnosed as metabolic abnormalities. The total incidence rate is 1:4153. Hyperphenylalaninemia and short-chain acyl-CoA dehydrogenase are the most common diseases in newborns. In addition, in 56 children, 39 (69.42 %) were diagnosed by genetic sequencing. Some hotspot mutations in 14 IEMs have been observed, including PAH gene c.728G > A, c.611A > G, and ACADS gene c. 1031A > G, c.164C > T. A total of 49,860 symptomatic patients were screened, of which 185 were diagnosed with IEM, with a detection rate of 0.37 %. The most commonly diagnosed diseases in high-risk infants aremethylmalonic acidemia and hyperphenylalaninemia. There are more clinical cases of congenital metabolic errors diagnosed by tandem mass spectrometry than newborn screening. The spectrum of diseases, prevalence, and genetic characteristics of normal newborns and high-risk children are quite different.