一例3-甲基戊烯二酸尿症Ⅶ型患儿的临床和遗传学分析

Clinical and genetic analysis of an infant with 3-methylglutaconic aciduria typeⅦ

目的对一例全面发育落后的婴儿进行临床和遗传学分析,明确其病因。方法采集患儿及其家系成员的病史,应用实验室检查、遗传代谢病筛查和新一代测序技术对该家系进行临床和遗传学分析。结果先证者临床表现为对声音反应不灵敏,竖头不稳,不能翻身、逗笑,不认识母亲。实验室检查血乳酸、血糖等正常,尿有机酸中3-甲基戊烯二酸、3-甲基戊二酸水平增高,提示为"3-甲基戊烯二酸尿症可能"。头颅磁共振扫描显示胼胝体压部T1W信号偏低,髓鞘化落后于月龄。高通量测序发现CLPB基因存在复合杂合变异c.1085G>A和c.1700A>C,分别遗传自父亲和母亲,二者均为新变异。根据美国医学遗传学与基因组学学会标准,两个变异均预测为疑似致病变异。结论该患儿可能为CLPB基因变异引起的3-甲基戊烯二酸尿症Ⅶ型。高通量测序技术为分析该类疾病提供了有力的诊断工具。

Objective To analyze the clinical and genetic characteristics of an infant girl featuring comprehensive developmental backwardness.Methods The patient was subjected to clinical examination,gas chromatography mass spectrometry and next-generation sequencing(NGS).Results The child was insensitive to sound,could not turn over,raise head,laugh,or recognize his mother.Laboratory tests were all normal,but metabolic analysis suggested 3-methylglutaconic aciduria due to elevated 3-methylglutaconic acid and 3-methylglutaric acid.NGS has detected two compound heterozygous CLPB variants in the child,namely c.1085G>A and c.1700A>C,which were respectively inherited from her father and mother.Bioinformatic analysis predicted both variants to be pathogenic.The patient was diagnosed with 3-methylglutaconic aciduria typeⅦ(MGCA7).Conclusion The MGCA7 in the child was probably caused by CLPB gene variants.NGS has provided a powerful diagnostic tool for this rare disorder.