Prevalence and Mutation Analysis of Short-Chain acyl-CoA Dehydrogenase Deficiency Detected by Newborn Screening in Hefei, China.

Abstract

Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is an autosomal recessive inborn error of mitochondrial fatty acid oxidation with highly variable biochemical and genetic characteristics. The present study aimed to estimate the prevalence and genetic characteristics of SCADD in newborns identified through screening. A total of 782,930 newborns were screened for SCADD in Hefei Neonatal Screening Center from January 2016 to December 2023. The blood samples from newborns were measured by tandem mass spectrometry (MS/MS). The suspected SCADD neonates were rechecked using next-generation gene sequencing for diagnosis. Sanger sequencing was used to verify the mutation site for patients with SCADD and their parents. A total of 21 SCADD cases were confirmed, with an incidence rate of 1/37,282. Genetic mutations were identified in all 21 cases, including 15 cases of compound heterozygous variation and 6 cases of homozygous variation. Twenty-one different mutation types and forty-two mutation sites were discovered, with the most frequent mutation being c.1031A>G, accounting for 21.43% (9/42), followed by c.1130C>T, accounting for 16.67% (7/42). Our findings expand the SCADD mutational spectra. c. 1031A>G and c.1130C>T are the common mutation sites for SCADD genes in newborns. SCADD diagnosed through NBS is primarily a benign condition, and early diagnosis is not necessarily essential.