单纯型甲基丙二酸血症患者诊治分析  

Diagnosis and treatment of isolated methylmalonic acidemia

作　　者：韩连书[1] 毋盛楠[1] 叶军[1] 邱文娟[1] 张惠文[1] 高晓岚[1] 王瑜[1] 李筱燕[1] 许浩[1] 顾学范[1] 

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、遗传代谢病研究室,200092

出　　处：《中华医学遗传学杂志》2013年第5期589-593,共5页Chinese Journal of Medical Genetics

基　　金：上海市卫生局科研课题（2009210）;上海市科委重大课题（11dzl950300）

摘　　要：目的探讨单纯型甲基丙二酸血症患者临床和遗传特点及治疗效果。方法对40例单纯型甲基丙二酸血症患者临床和遗传学特点、诊治及转归进行分析。治疗方法包括限制天然蛋白质摄人量，补充特殊奶粉、左旋肉碱及维生素B。随访内容包括发育情况、血丙酰肉碱及尿甲基丙二酸水平。结果40例确诊患者中，33例患者接受MUT基因分析，30例检出突变，占90．9％；随访30例，随访时间1个月至8年，死亡8例，存活22例中8例智力正常（其中4例来自新生儿筛查者治疗前后均无临床症状），14例遗留不同程度运动、语言发育迟缓及智力低下。治疗后患者血丙酰肉碱、丙酰肉碱：乙酰肉碱比值、尿甲基丙二酸及甲基枸橼酸水平中位数分别由24．15μmol／L 1．08、705．34和7．71降至10．50μmol／L、0.63、166．23及3．96，差异有统计学意义（均P〈0．05）。结论单纯型甲基丙二酸血症患者预后与患病类型、发病年龄及对维生素B12治疗的反应性等因素有关，新生儿期发病、维生素B12治疗无效者预后差。Objective To explore the clinical feature, therapeutic effect and prognosis of isolated methylmalonic acidemia. Methods The clinical characteristics, laboratory findings, treatment and outcome of 40 patients were restrospectively analyzed. The main treatment was a low-protein diet supplemented with L-carnitine and special milk free of leucine, valine, threonine and methionine. Vitamin B12 was also given to cobalamin responders. The patients were followed up every 1-3 months. Results Mutations in the MUT gene were identified in 30 of 33 patients who had accepted detection of DNA sequencing. Thirty cases were treated and followed up regularly for 1 month to 8 years. Eight cases had died, 8 had developed normal intelligence, of which 4 from newborn screening were asymptomatic. Psychomotor developmental delay and mental retardation were present in 14 cases. The propionylcarnitine level, ratio of propionylearnitine/ acetylcarnitine in blood, methylmalonic acid and methylcitric acid levels in urine have decreased significantly, with the median values respectively reduced from 24. 15（7.92-81.02）μmol/L, 1. 08（0. 38-6. 01）, 705. 34 （113.79-3078.60） and 7. 71（0. 52-128. 21） to 10. 50（3. 00-30. 92） μmol/L, 0. 63（0. 25-2.89）, 166. 23 （22.40-3322.21） and 3.96（0.94-119.13） （P〈0.05）. Conclusion The prognosis of isolated methylmalonic acidemia may be predicted with the enzymatic subgroup, age at onset and cobalamin responsiveness. Outcome is unfavorable in neonatal patients and those who were non-responsive to cohalamin.

关 键 词：甲基丙二酸血症 甲基丙二酸 丙酰肉碱 治疗 

分 类 号：R725.8[医药卫生—儿科]