甲基丙二酸血症MMACHC基因c.482G>A突变患者临床资料及随访分析  

Clinical analysis and outcome of patients with c.482G>A variant of MMACHC gene in cblC type methylmalonic acidemia

作　　者：鄂慧姝 韩连书[1] 叶军[1] 邱文娟[1] 张惠文[1] 梁黎黎[1] 王瑜[1] 王建国 季文君[1] 陈婷[1] 顾学范[1] E Huishu;Han Lianshu;Ye Jun;Qiu Wenjuan;Zhang Huiwen;Liang Lili;Wang Yu;Wang Jianguo;Ji Wenjun;Chen Ting;Gu Xuefan(Department of Pediatric Endocrinology and Genetic Metabolism,Shanghai Institute for Pediatric Research,Xinhua Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200092,China)

机构地区：[1]上海交通大学医学院附属新华医院,上海市儿科医学研究所,小儿内分泌遗传科,200092

出　　处：《中华内分泌代谢杂志》2019年第7期581-585,共5页Chinese Journal of Endocrinology and Metabolism

基　　金：国家重点研发计划(2016YFC-0901505);上海市体育局科研项目(15Z028).

摘　　要：目的了解甲基丙二酸血症(methylmalonic acidemia,MMA)MMACHC基因c.482G>A(p.R161Q)突变患者临床表现、治疗效果及预后。方法回顾性分析75例携带MMACHC基因c.482G>A(p.R161Q)突变的MMA患者的临床表现、质谱检测结果、基因突变类型、治疗效果及预后。结果75例患者中57例(76%)来自新生儿筛查,仅1例发病;18例未筛查患者中2例因同胞确诊而检测后诊断本病,未发病,余16例均为临床病例。17例发病患者中,发病年龄中位数为12岁(10 d^26岁)。其中迟发型患者12例(70.6%),主要表现为学习成绩下降、记忆减退、表达不畅、运动能力倒退;早发型患者5例(29.4%)以抽搐、发育落后多见。全部患者均为维生素B12有效型。治疗后患者血中丙酰肉碱、丙酰肉碱与乙酰肉碱比值、尿中甲基丙二酸、甲基枸橼酸及血同型半胱氨酸水平均下降(P<0.01)。经新生儿筛查确诊患者均发育正常。发病患者中3例经治疗发育正常,其余患者遗有不同程度的智力和(或)运动能力障碍。结论MMACHC基因c.482G>A(p.R161Q)突变与迟发型MMA相关,对羟钴胺的反应优于其他突变类型。来自新生儿筛查确诊的患者预后良好,一旦发病,致残率较高,故新生儿筛查是预防此病的较好方法。Objective To explore the clinical manifestations, treatment and outcomes of patients with c. 482G>A(p.R161Q)variant of MMACHC gene in cblC type methylmalonic acidemia(MMA). Methods The clinical manifestations, mass spectrometry results, genotypes, treatment and outcomes of 75 patients with cblC type MMA carrying c. 482G>A(p.R161Q)variant were retrospectively analyzed. Results Of the 75 patients, 57(76%)were from newborn screening and one of them had an onset. Among the rest 18 unscreened patients, 2 were diagnosed after their full sisters′ or brothers′ diagnosis, the others were clinical patients. There were 17 clinical patients, with the medium age of onset 12 years old(10 days^26 years old). 12 late onset patients(70.6%)presented with poor academic performance, memory loss, poor expression, and decreased exercise capacity, while 5 early onset patients(29.4%)presented with convulsion and delay of development. All patients were vitamin B12-responsive. The levels of blood propionylcarnitine, the ratio of propionylcarnitine to acetylcarnitine, urinary methylmalonic acid and methyldecanoic acid, and plasma homocysteine were significantly decreased after treatment(P< 0.01). All patients diagnosed from newborn screening had normal development. However, only 3 clinical patients had a rather normal outcomes and the others remained different levels of intelligence and(or)motor dysfunction after treatment. Conclusion The c. 482G>A(p.R161Q)variant of MMACHC gene is associated with late onset cblC type MMA. Patients with this variant have a better response to hydroxycobalamin than other variants. The outcome of patients diagnosed from the newborn screening is good. When symptoms occur, the disability rate is often high. Therefore, newborn screening is a recommended method to prevent this disease.

关 键 词：甲基丙二酸血症 MMACHC基因 甲基丙二酸 丙酰肉碱 

分 类 号：R722[医药卫生—儿科]