琥珀酰辅酶A连接酶缺陷导致继发性甲基丙二酸尿症四例的临床与实验室研究  

Clinical and laboratory studies on four Chinese patients with succinate-CoA ligase deficiency noticed by mild methylmalonic aciduria

作　　者：刘玉鹏[1] 李溪远[1] 丁圆[1] 王峤[1] 宋金青[1] 张尧[1] 李东晓[1] 秦亚萍 杨艳玲[1] 

机构地区：[1]北京大学第一医院儿科,100034 [2]北京福佑龙惠遗传病专科门诊部

出　　处：《中华儿科杂志》2016年第5期365-369,共5页Chinese Journal of Pediatrics

基　　金：国家自然科学基金（81471097）;“十二五”国家科技支撑计划（2012BA109804）

摘　　要：【摘要】目的探讨因琥珀酰辅酶A连接酶缺陷导致的继发性甲基丙二酸尿症患儿的临床与基因特点。方法对2011年2月至2014年4月北京大学第一医院儿科确诊的琥珀酰辅酶A连接酶缺陷导致的甲基丙二酸尿症中国患儿4例的临床经过、生化异常、脑影像特点及基因突变进行研究。结果4例患儿于生后1d至6个月发病，于6个月至2岁8个月就诊，均有智力运动落后，喂养困难，肌张力低下，3例合并难治性癫痫，听力障碍。血清乳酸、丙酮酸均增高。尿甲基丙二酸9．21～9．97mmol／mol肌酐（正常值0．2～3．6mmol／mol肌酐），血液丙酰肉碱5．07～8．15μmol／L（正常值0．5～4．0μmol／L），琥珀酰肉碱1．98～4．49txmol／L（正常值0．15～1．0μmol／L）。外周血白细胞线粒体呼吸链酶复合物存在单一或复合缺陷。头颅MRI显示基底节损害或脑萎缩。3例为SUCLGl基因缺陷，共检出5种突变（c．809A〉C、c．826—2A〉G、c．550G〉A、c．751C〉T和c．961C〉G突变）。1例为SUCLA2c．970C〉T纯合突变，为新突变。经治疗后，4例患儿智力运动缓慢进步。结论琥珀酰辅酶A连接酶缺陷患儿起病早，临床表现缺乏特异性，预后不良。对于轻度甲基丙二酸尿症伴严重神经系统损害及高乳酸血症的患者需注意鉴别琥珀酰辅酶A连接酶缺陷症尿症，基因诊断是关键方法。Objective To study the clinical and genetic features of the patients with secondary methylmalonic aciduria due to succinate-CoA ligase deficiency. Method From February 2011 to April 2014, 4 Chinese patients with succinate-CoA ligase deficiency and mild methylmalonic aciduria were enrolled in this study. The clinical course, biochemical features, brain MRI findings, and mutations were analyzed. Result Four patients presented with severe psychomotor retardation, hypotonia, seizures, feeding problems and failure to thrive from the age of one day to 6 months. Three of them had intractable epilepsies. One had hearing defect. Mild methylmalonic aciduria was detected by elevated urine methylmalonie acid and blood propionylcarnitine at the age of 6 months to 2 years and 8 months. Five mutations, c. 550G 〉 A, c. 751C 〉 T, c. 809A 〉 C, c. 961C 〉 G and c. 826-2A 〉 G in SUCLG1 of three patients were identified. On SUCLA2, one novel mutation, c. 970C 〉 T, was found in one patient. After treatment, the disease in all four patients was improved. Conclusion Four Chinese patients with succinyl-CoA ligase deficiency caused by SUCLG1 and SUCLA2 mutations were noticed by mild methylmalonic aeiduria and diagnosed using high-throughput genomic sequencing. Succinate-CoA ligase deficiency is a rare cause of methylmalonie aciduria. Biochemical and gene studies are necessary for the differential diagnoses.

关 键 词：甲基丙二酸 琥珀酰CoA连接酶类 DNA 线粒体 SUCLG1 SUCLA2 

分 类 号：R725.8[医药卫生—儿科]