Errors Of Metabolism In Newborns Research Articles

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

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.

Occurrence of Inborn Errors of Metabolism in Newborns, Diagnosis and Prophylaxis.

Inborn errors of metabolism (IEM) are a heterogeneous group of rare genetic disorders that are generally transmitted as autosomal or X-linked recessive disorders. These defects arise due to mutations associated with specific gene(s), especially the ones associated with key metabolic enzymes. These enzymes or their product(s) are involved in various metabolic pathways, leading to the accumulation of intermediary metabolite(s), reflecting their toxic effects upon mutations. The diagnosis of these metabolic disorders is based on the biochemical analysis of the clinical manifestations produced and their molecular mechanism. Therefore, it is imperative to devise diagnostic tests with high sensitivity and specificity for early detection of IEM. Recent advances in biochemical and polymerase chain reaction-based genetic analysis along with pedigree and prenatal diagnosis can be life-saving in nature. The latest development in exome sequencing for rapid diagnosis and enzyme replacement therapy would facilitate the successful treatment of these metabolic disorders in the future. However, the longterm clinical implications of these genetic manipulations is still a matter of debate among intellectuals and requires further research.