浙江省新生儿多酰基辅酶A脱氢酶缺乏症筛查及随访分析  

Screening of multiple acyl-CoA dehydrogenase deficiency in newborns and follow-up of patients

作　　者：周朵[1] 叶梅玲 胡真真[1] 张玉 朱琳 杨茹莱[1] 黄新文[1] ZHOU Duo;YE Meiling;HU Zhenzhen;ZHANG Yu;ZHU Lin;YANG Rulai;HUANG Xinwen(Department of Genetics and Metabolism,Children’s Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,National Children’s Regional Medical Center,Hangzhou 310052,China;Taizhou Hospital of Zhejiang Province,Taizhou Enze Medical Center(Group),Taizhou 317000,Zhejiang Province,China;Zhejiang Biosan Biochemical Technology Co.,Ltd.,Hangzhou 310012,China)

机构地区：[1]浙江大学医学院附属儿童医院遗传与代谢科国家儿童健康与疾病临床医学研究中心国家儿童区域医疗中心,浙江杭州310052 [2]浙江省台州医院台州恩泽医疗中心(集团),浙江台州317000 [3]浙江博圣生物技术股份有限公司,浙江杭州310012

出　　处：《浙江大学学报（医学版）》2021年第4期454-462,共9页Journal of Zhejiang University(Medical Sciences)

基　　金：国家重点研发计划(2018YFC1002204);国家自然科学基金(82073560);浙江省公益技术研究计划(LGC19B050013)。

摘　　要：目的:了解浙江省新生儿多酰基辅酶A脱氢酶缺乏症(MADD)的发病率、临床特征及基因突变特点。方法:采用串联质谱法对2009年1月至2020年12月浙江省新生儿疾病筛查中心3896789名新生儿进行遗传代谢病筛查,结合尿有机酸分析及电子转移黄素蛋白(ETF)或电子转移黄素蛋白脱氢酶(ETFDH)基因检测确诊。确诊患儿进行饮食和生活管理,补充左卡尼汀、核黄素、辅酶Q10治疗,长期随访并评估患儿的生长和智力发育情况。结果:确诊MADD患儿13例,除1例为Ⅱ型,其余均为Ⅲ型(迟发型),发病率为1/299753。13例患儿中,1例死亡,4例因感染诱发以低血糖为主要表现的急性代谢失调,1例出现肌张力降低,其余患儿随访发育良好(随访时间3~45个月)。患儿初筛血C4~C18:1不同程度升高。13例患儿进行基因检测,其中ETFA基因复合杂合突变1例,ETFA基因纯合突变1例,ETFB基因复合杂合突变1例,ETFDH基因复合杂合突变8例,ETFDH基因纯合突变1例,仅检测出一个ETFDH基因突变位点1例。c.250G>A为热点突变。结论:MADD临床表现高度异质,新生儿期发病较为严重,迟发型常无明显临床症状,初筛血C4~C18:1不同程度升高,最常见基因突变为c.250G>A。Objective:To investigate the incidence rate,clinical and gene mutation characteristics of multiple acyl-CoA dehydrogenase deficiency(MADD) in newborns in Zhejiang province.Methods:A total of 3 896 789 newborns were screened for MADD using tandem mass spectrometry in Zhejiang Neonatal Screening Center during January 2009 and December 2020.Patients of MADD were confirmed by urine organic acid and electron transferring flavoprotein(ETF) or electron transferring flavoprotein dehydrogenase(ETFDH) gene detection.MADD patients were given diet and life management,supplemented with L-carnitine,riboflavin and coenzyme Q 10 treatment,and their growth and intellectual development were evaluated during the followed up.Results:Thirteen patients with MADD were diagnosed,with an incidence of 1/299 753.One patient was type Ⅱ,and the rest were type Ⅲ.Patients were followed up for 3-45 months,1 case died,4 cases had acute metabolic disorders with hypoglycemia as the main manifestation due to infection,1 case had hypotonia,and the rest 7 cases developed well.Patients had raised levels of C4-C18:1 acylcarnitines in the initial screening.Thirteen children were genetically tested,1 case with compound heterozygous mutation in the ETFA gene,1 case with homozygous mutation in the ETFA gene,1 case with compound heterozygous mutation in the ETFB gene,8 cases with compound heterozygous mutation and 1 case with homozygous mutation in the ETFDH gene,1 case that only 1 locus of ETFDH gene was detected.The c.250 G>A was the hotspot mutation in this study.Conclusion:The clinical manifestations of MADD are highly heterogeneous.The neonatal-onset form is serious,and late onset form usually has no obvious clinical symptoms.C4-C18:1 acylcarnitines usually increased in the initial screening,and the hotspot gene mutation is c.250 G>A.

关 键 词：新生儿筛查 多酰基辅酶A脱氢酶缺乏症 电子转移黄素蛋白 电子转移黄素蛋白脱氢酶 串联质谱法 

分 类 号：R722.11[医药卫生—儿科] R596[医药卫生—临床医学]