徐州地区异丁酰辅酶A脱氢酶缺乏症筛查临床特征及基因分析

Clinical characteristics and genetic analysis of isobutyryl CoA dehydrogenase deficiency in Xuzhou:population screening results

目的总结分析徐州地区异丁酰辅酶A脱氢酶缺乏症(isobutyryl-CoA dehydrogenase deficiency, IBDD)筛查临床特征及基因变异特点。方法回顾性选择徐州地区2016年10月至2021 年10月完成串联质谱技术检测、诊断为IBDD的新生儿为研究对象, 分析患儿临床表型、基因变异类型及临床诊疗和随访情况。结果研究期间徐州地区共510 057名新生儿参与筛查, 确诊IBDD 10例。10例患儿筛查及随访均呈现丁酰基肉碱及其相关比值增高;1例出现短暂转氨酶升高, 1例出现语言发育落后, 其余8例无特异性临床表现。共发现酰基辅酶A脱氢酶家族成员8基因变异位点16个, 其中10个未报道过的变异位点为c.567+8C>T、c.213G>T、c.553C>T、c.1190T>C、c.1060G>A、c.494G>A、c.771C>A、c.962A>T、c.715A>G和c.731G>A。基因变异见于Exon3、Exon4、Exon5、Intron5、Exon7、Exon9、Exon10。热点变异为c.1176G>T、c.286G>A、c.1000C>T。结论 IBDD为罕见病, 临床表现无特异性, 新生儿遗传代谢病筛查联合尿有机酸检测及基因检测技术可对IBDD实现早发现、早诊断, 短期随访IBDD患儿未见明显不良结局, 建议长期随访。

Objective To study the clinical features and genetic characteristics of isobutyryl-CoA dehydrogenase deficiency(IBDD)of neonates in Xuzhou area.Methods From October 2016 to October 2021,neonates diagnosed with IBDD using tandem mass spectrometry in Xuzhou area were retrospectively studied.Their clinical phenotypes and genotypes,clinical diagnosis,treatment and follow-up were analyzed.Results A total of 510057 neonates were screened and 10 cases of IBDD were diagnosed.The 10 IBDD cases showed increased butyryl carnitine(C4),C4/C2 and C4/C3 during screening and follow-up tests.One case had transient elevated transaminase and one case showed delayed language development.The other 8 cases were otherwise normal.A total of 16 mutation loci of acyl-CoA dehydrogenase 8(ACAD8)gene were found,including 10 unreported loci:c.567+8C>T,c.213G>T,c.553C>T,c.1190T>C,c.1060G>A,c.494G>A,c.771C>A,c.962A>T,c.715A>G and c.731G>A.Genetic mutations were found in Exon 3,Exon 4,Exon 5,Intron 5,Exon 7,Exon 9 and Exon 10.The hot spots of mutations were c.1176G>T,c.286G>A and c.1000C>T.Conclusions IBDD is a rare disease without specific clinical manifestations.Neonatal metabolic disease screening combined with urinary organic acid tests and genetic sequencing can be used for early detection and diagnosis of IBDD.No serious adverse outcome is found in IBDD patients during short-term follow-up,however,long-term follow-up is recommended.