Medical Genetics, Zibo Maternal and Child Health Hospital, Zibo, Shandong Province, P.R. China.
J Pediatr Endocrinol Metab. 2022 Sep 8;35(10):1264-1271. doi: 10.1515/jpem-2022-0394. Print 2022 Oct 26.
Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is an autosomal recessive disorder of the fatty acid oxidative metabolism. This study aimed to investigate the epidemiological characteristics, the spectrum of variation, clinical phenotype, and prognosis of MCADD 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 of carnitine in the blood spots and for diagnosis.
A total of 183,082 newborns were detected, and six patients were diagnosed with MCADD (1/3,0514). The primary octanoylcarnitine (C8) and the octanoylcarnitine/decanoylcarnitine ratio (C8/C10) were elevated in all patients. 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, and the most common pathogenic variant is c.449_452 del CTGA (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.
中链酰基辅酶 A 脱氢酶缺乏症（MCADD）是脂肪酸氧化代谢的常染色体隐性遗传病。本研究旨在调查中国新生儿 MCADD 的流行病学特征、变异谱、临床表型和预后。
我们回顾性分析了 2016 年 1 月至 2022 年 3 月淄博地区的新生儿筛查（NBS）数据，并总结了最近在中国新生儿中报告的 42 例病例。采用高效液相色谱-串联质谱（HPLC-MS/MS）和下一代测序（NGS）检测血斑中肉碱浓度并进行诊断。
共检测了 183082 例新生儿，诊断出 6 例 MCADD 患者（1/30514）。所有患者的原发性辛酰肉碱（C8）和辛酰肉碱/癸酰肉碱比值（C8/C10）均升高。基因分析显示 ACADM 基因有 4 个已知和 4 个新的变异。5 例患者无症状，在饮食指导下正常发育。1 例患儿因接种疫苗诱发 MCADD 死亡，表现为低血糖和酰基肉碱升高。
中国新生儿 MCADD 的发病率存在地域差异，为 1/222903 至 1/30514，最常见的致病变异是 ACADM 基因中的 c.449_452delCTGA（p.T150Rfs*4），频率为 27.7%。HPLC-MS/MS 和遗传分析有助于 MCADD 的早期预防和良好预后。
