Tandem Mass Spectrometry Screening for Inborn Errors of Metabolism in Newborns and High-Risk Infants in Southern China: Disease Spectrum and Genetic Characteristics in a Chinese Population

Abstract

Inborn errors of metabolism (IEMs) often causing progressive and irreversible neurological damage, physical and intellectual development lag or even death, and serious harm to the family and society. The screening of neonatal IEMs by tandem mass spectrometry (MS/MS) is an effective method for early diagnosis and presymptomatic treatment to prevent severe permanent sequelae and death. A total of 111,986 healthy newborns and 7,461 hospitalized high-risk infants were screened for IEMs using MS/MS to understand the characteristics of IEMs and related gene mutations in newborns and high-risk infants in Liuzhou. Positive samples were analyzed by Sanger sequencing or next-generation sequencing. The results showed that the incidence of IEMs in newborns in the Liuzhou area was 1/3,733, and the incidence of IEMs in high-risk infants was 1/393. Primary carnitine deficiency (1/9,332), phenylketonuria (1/18,664), and isovaleric acidemia (1/37,329) ranked the highest in neonates, while citrullinemia type II ranked the highest in high-risk infants (1/1,865). Further, 56 mutations of 17 IEMs-related genes were found in 49 diagnosed children. Among these, HPD c.941T > C, CBS c.1465C > T, ACADS c.337G > A, c.1195C > T, ETFA c.737G > T, MMACHC 1076bp deletion, PCCB c.132-134delGACinsAT, IVD c.548C > T, c.757A > G, GCDH c.1060G > T, and HMGCL c.501C > G were all unreported variants. Some related hotspot mutations were found, including SLC22A5 c.51C > G, PAH c.1223G > A, IVD c.1208A > G, ACADS c.625G > A, and GCDH c.532G > A. These results show that the overall incidence of IEMs in the Liuzhou area is high. Hence, the scope of IEMs screening and publicity and education should be expanded for a clear diagnosis in the early stage of the disease.