单纯型甲基丙二酸尿症126例的临床表型与基因型研究  

Phenotypes and genotypes of 126 patients with isolated methylmalonic aciduria

作　　者：刘玉鹏[1] 丁圆[1] 李溪远[1] 宋金青[1] 吴桐菲[2] 王立文[3] 李梦秋 秦亚萍 黄昱[5] 杨艳玲[1] 

机构地区：[1]北京大学第一医院儿科,100034 [2]首都医科大学右安门临床检验中心 [3]首都儿科研究所附属儿童医院神经科 [4]北京福佑龙惠遗传专科诊所 [5]北京大学医学部医学遗传系

出　　处：《中华实用儿科临床杂志》2015年第20期1538-1541,共4页Chinese Journal of Applied Clinical Pediatrics

基　　金：“十二五”国家科技支撑计划项目（2012BAl03802）;国家自然科学基金（81471097）;儿科遗传性疾病分子诊断与研究北京市重点实验室

摘　　要：目的：探讨单纯型甲基丙二酸尿症患者的临床、生化及基因特点。方法选取2001年1月至2014年12月北京大学第一医院诊断的126例单纯型甲基丙二酸尿症患者，男81例，女45例。其中60例行基因分析。对患儿的临床经过、生化特点、影像学异常、基因型及预后等进行研究。结果126例患儿中仅3例（2.4％）为新生儿筛查发现，于1个月左右开始饮食与维生素 B12、左卡尼汀支持治疗，无症状；123例（97.6％）患儿为临床高危筛查发现，于出生后数小时~7岁11个月发病，主要表现为反复呕吐、喂养困难、发育落后、嗜睡、呼吸困难、昏迷、抽搐、皮肤损害、黄疸等。27例（21.4％）有异常家族史，有同胞不明原因死亡或残障。一般辅助检查常见异常为代谢性酸中毒、贫血。头颅 MRI 异常以双侧基底核对称性损害及白质改变为主。60例接受基因分析的患者中，MUT 缺陷58例，MMAA 缺陷、MMAB 缺陷各1例。MUT 基因缺陷中共检出46种突变，其中12种为新突变。112例患儿经治疗后临床症状改善，但仍遗留不同程度的智力运动障碍及多脏器损伤。11例（8.73％）患儿死亡。仅3例智力运动发育正常。结论单纯型甲基丙二酸尿症患者临床表现复杂，易出现代谢危象，MUT 基因缺陷是主要病因，早期诊断、合理治疗至关重要。新生儿筛查是早期发现甲基丙二酸尿症的关键。Objective To investigate the clinical,biochemical and genetic findings in patients with isolated methylmalonic aciduria. Methods From January 2001 to December 2014,a total of 126 patients with isolated methyl-malonic aciduria from Peking University First Hospital were enrolled in this study. In 60 patients,gene analysis was per-formed. The clinical characteristics,laboratory findings,treatment and outcomes were retrospectively analyzed. Results Among the 126 patients,only 3 cases（2. 4% ）were detected through newborn screening and treated with dietary in-tervention,cobalamin and L - camitine. The age at onset of 123 cases（97. 6% ）varied from a few hours after birth to 7 years and 11 months old. The common presentations were recurrent vomiting,mental retardation,poor feeding,lethargy, respiratory distress,coma,seizures,cutaneous lesion and jaundice with 11 patients（8. 73% ）dead. Abnormal family his-tory was found in 27（21. 4% ）patients. Metabolic acidosis and anemia were frequent laboratory findings. Basal ganglia damage and white matter changes were observed in most patients. Sixty patients got genetic analysis,and 58 cases of them had MUT gene mutations. One case had MMAA defect. One case had MMAB defect. In MUT gene,12 novel muta-tions were identified. After treatment,mild to severe psychomotor retardation was observed in 112 patients with isolated methylmalonic aciduria. Conclusions The clinical manifestation of patients with isolated methylmalonic aciduria is complex,and prone to appear metabolic crisis. MUT defect is the main cause. Early metabolic investigation is very im-portant to reach diagnosis. Newborn screening,early diagnosis and adequate therapy are key points to reduce the morta-lity and handicap.

关 键 词：有机酸尿症 甲基丙二酸尿症 MUT MMAA MMAB 遗传代谢病 

分 类 号：R725.8[医药卫生—儿科]