极长链酰基辅酶A脱氢酶缺乏症的筛查、基因变异分析及随访研究

Newborn screening,gene variation analysis and follow-up study of very long chain acyl CoA dehydrogenase deficiency

目的了解河南省新生儿极长链酰基辅酶A脱氢酶缺乏症(VLCADD)的患病率、基因变异特点及预后。方法采用串联质谱分析技术对2013年1月至2019年12月河南省867103例新生儿行遗传代谢病筛查,对确诊VLCADD患儿及家系进行二代测序技术靶向测序及Sanger测序验证,分析其临床、生化改变及基因变异特点,进行饮食指导,随访观察其生长发育情况。结果共确诊VLCADD新生儿6例,河南省新生儿VLCADD患病率为1/144517。发现ACADVL基因变异11种,包括5种新发变异c.692-2_692-1delAG、c.753-23_753-22del、c.960delG、c.1361A>G、c.1955C>T。对确诊新生儿给予高碳水化合物、低脂饮食,随访8~56个月,除2例患儿死亡外,其余患儿预后良好。结论河南省新生儿VLCADD患病率为1/144517。本研究结果丰富了ACADVL基因突变谱,为VLCADD筛查和诊断提供了重要依据。

Objective To investigate the prevalence,gene variation and prognosis of very long chain acyl CoA dehydrogenase deficiency(VLCADD)in newborns in Henan Province.Methods From January 2013 to December 2019,867103 newborns were investigated for VLCADD by tandem mass spectrometry.Children who diagnosed as VLCADD and their families were subjected to next-generation sequencing and Sanger sequencing.Clinical data,biochemical changes and gene variation characteristics of the confirmed cases of VLCADD were analyzed.Dietary guidance was given,and their growth and development were followed up.Results Six neonates were diagnosed as VLCADD,and the prevalence of VLCADD in the Henan Province was 1/144517.A total of 11 mutations in the ACADVL gene were found,including 5 new variants c.692-2_692-1delAG,c.753-23_753-22del,c.960delG,c.1361A>G,and c.1955C>T.The newborns were given a high-carbohydrate,low-fat diet,and followed up for 8-56 months.Except for two deaths,all patients had a good outcome.Conclusions The prevalence of neonatal VLCADD in Henan Province is 1/144517.This results has enriched the ACADVL gene mutation spectrum and provided an important basis for the screening and diagnosis of VLCADD.