Newborn screening and genetic variation of medium chain acyl-CoA dehydrogenase deficiency in the Chinese population.

Abstract

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is an autosomal recessive disorder of thefatty acid oxidative metabolism. This study aimed toinvestigate the epidemiological characteristics, the spectrum of variation, clinical phenotype, and prognosis ofMCADD in Chinese newborns. We retrospectively analysed newborn screening (NBS) data in the Zibo area from January 2016 to March 2022 and summarized 42 cases recently reported in Chinese neonates. High-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) and next-generation sequencing (NGS) were used to detect the concentrations ofcarnitine in the blood spots and for diagnosis. A total of 183,082 newborns were detected, andsix patients were diagnosed with MCADD (1/3,0514). The primary octanoylcarnitine (C8) and the octanoylcarnitine/decanoylcarnitine ratio (C8/C10) were elevated in allpatients. Gene analysis revealed four known and four novel variants of the ACADM gene. Five patients were asymptomatic and developed normally under dietary guidance. One child died of vaccination-induced MCADD, presenting with hypoglycemia and elevated acylcarnitines. The incidence of MCADD in Chinese newborns varies geographically from 1/222,903 to 1/30,514, andthe most common pathogenic variant isc.449_452 delCTGA (p. T150Rfs∗4) in ACADM gene with a frequency of 27.7%. HPLC-MS/MS and genetic analysis are beneficial for early prevention and good prognosis of MCADD.