Expanded newborn screening for inherited metabolic disorders and genetic characteristics in a southern Chinese population

摘要

To evaluate the incidence, disease spectrum, and genetic characteristics of inherited metabolic disorders (IMDs) of newborns in Quanzhou area, China. We analyze the expanded newborn screening results of IMDs detected by tandem mass spectrometry (MS/MS) during 5 years. Suspected positive patients were diagnosed through next-generation sequencing and validated by Sanger sequencing. In addition, multiplex ligation-dependent probe amplification technology has also been applied to assist in diagnosis of diseases with deletion or duplication mutations. A total of 364,545 newborns were screened, 130 IMDs were identified yielding an incidence of 1:2804. In addition, 9 cases of maternal disorders were also identified by our MS/MS newborn screening program. There were 42 newborns with amino acid disorders (1:8680), 39 with organic acid disorders (1:9347), and 49 with fatty acid oxidation disorders (1:7440). Unlike other studies, our study indicated that fatty acid oxidation disorder has the highest proportion (37.7%), particularly primary carnitine deficiency (PCD) with incidence up to 1:10,126 was the most common disorder in the region. The recurrent mutations of relatively common diseases like PCD, phenylalanine hydroxylase deficiency, short-chain acyl-CoA dehydrogenase deficiency, citrin deficiency, glutaric acidemia type I, isobutyryl-CoA dehydrogenase deficiency, and multiple acyl-CoA dehydrogenase deficiency in this region were also clearly elucidated. Therefore, our data indicated that IMDs are never uncommon in Quanzhou, the disease spectrum and genetic backgrounds were clearly elucidated, contributing to the treatment and prenatal genetic counseling of these disorders in this region.