甲基丙二酸尿症cblB型1例及其MMAB基因新突变  

A Chinese boy with methylmalonic aciduria cblB type and a novel mutation in the MMAB gene

作　　者：刘玉鹏[1] 王海军[2] 吴桐菲[3] 李溪远[1] 宋金青[1] 丁圆[1] 张尧[1] 王峤[1] 杨艳玲[1] 

机构地区：[1]北京大学第一医院儿科,北京100034 [2]郑州市儿童医院,河南郑州450000 [3]首都医科大学右安门临床检验中心,北京100069

出　　处：《中国当代儿科杂志》2015年第2期172-175,共4页Chinese Journal of Contemporary Pediatrics

基　　金："十二五"国家科技支撑计划项目(2012BAI09B04)

摘　　要：cblB缺陷是甲基丙二酸尿症中的罕见类型,该文首次报道1例中国cblB型甲基丙二酸尿症患儿,就其临床经过、血液酯酰肉碱谱、尿液有机酸分析、基因缺陷进行研究。该患儿以代谢性脑病形式起病,液相串联质谱分析显示患儿血液丙酰肉碱显著增高（22.43μmol/L,参考值1.0~5.0μmol/L）,丙酰肉碱/乙酰肉碱比值轻度增高（0.51,参考值0.03~0.50）,尿液甲基丙二酸（195.41 mmol/mol肌酐,正常值0.2~3.6 mmol/mol肌酐）及其代谢产物浓度增高,血清总同型半胱氨酸浓度正常,符合单纯型甲基丙二酸血症。患儿MUT基因分析未见突变,MMAB基因存在c.562G〉A（p.V188M）和c.577G〉A（p.E193K）杂合突变,确诊为cblB型甲基丙二酸尿症。其中,c.562G〉A为新突变。经羟钴铵肌肉注射、口服左卡尼汀、低蛋白饮食及特殊配方奶粉治疗后,患儿病情逐渐好转。随访至患儿3岁11个月,智力运动明显进步。cblB缺陷患者缺乏特异性症状,临床表型为单纯型甲基丙二酸尿症,可通过代谢筛查及MMAB基因分析获得确诊。cblB defect is a rare type of methylmalonic aciduria. In this study, a Chinese boy was diagnosed with methylmalonic aciduria cblB type and a novel mutation in the MMAB gene. The clinical presentations, blood acylcarnitines profiles, urine organic acids and genetic features of the patient were reported. The boy presented with fever, feeding difficulty and lethargy at the age of 2 months. Seven days later, he had coma, cold limb, thrombocytopenia, metabolic acidosis and liver damage. His blood propionylcarnitine and urinary methylmalonic acid levels increased significantly, but the plasma total homocysteine level was in the normal range, which supported the diagnosis of isolated methylmalonic aciduria. Gene analysis was performed by direct sequencing. No mutation in the MUT gene was found. However, a reported mutation c.577G〉A（p.E193K） and a novel mutation c.562G〉A（p.V188M） in the MMAB gene were identified, which confirmed the diagnosis of methylmalonic aciduria cbl B type. Progressive clinical and biochemical improvement has been observed after hydroxylcobalamin injection, protein-restricted diet with the supplements of special formula and L-carnitine. He is currently 3 years and 11 months old and has a normal development condition. The phenotypes of the patients with cbl B defect are nonspecific. Metabolic analysis and MMAB gene analysis are keys for the diagnosis of the disorder.

关 键 词：甲基丙二酸尿症 cblB型 MMAB基因 新突变 代谢性脑病 

分 类 号：R725.8[医药卫生—儿科]