甲基丙二酸血症患者临床特征及基因突变分析  

Clinical features and genetic mutation analysis of methylmalonic acidemia patients

作　　者：李璐 张改秀[2] 阎亚琼[3] 陈欢 韩蕊 LI Lu;ZHANG Gaixiu;YAN Yaqiong;CHEN Huan;HAN Rui(Department of Pediatric Internal Medicine,Shanxi Medical University,Taiyuan 030001,China;Department of Endocrinology and Genetic Metabolism,Children’s Hospital of Shanxi Pro-vince;Department of Child Health Division,Children’s Hospital of Shanxi Province)

机构地区：[1]山西医科大学儿科医学系小儿内科教研室,太原030001 [2]山西省儿童医院内分泌与遗传代谢科 [3]山西省儿童医院儿保科

出　　处：《山西医科大学学报》2020年第9期986-994,共9页Journal of Shanxi Medical University

摘　　要：目的总结甲基丙二酸血症(MMA)患儿的临床特征并分析患者基因突变类型,为其临床诊断与治疗提供参考,以提高对该病的认识。方法收集2013年1月至2019年12月于山西省儿童医院就诊的43例甲基丙二酸血症病人,回顾性分析其临床资料(起病年龄、首发症状、辅助检查、基因结果等),随访其治疗效果。结果MMA患儿首发症状为纳差、反应及精神差9例、智力及运动发育迟滞14例、面色苍白2例、反复呕吐6例、呼吸困难3例、抽搐2例,无明显临床症状7例(新筛发现),可合并嗜睡、营养不良、癫痫、代谢性酸中毒等。化验检查结果示,7例高氨血症、11例高乳酸血症、17例贫血、12例代谢性酸中毒、4例血小板减少、7例高丙酮酸血症、13例心肌酶谱异常、9例肝功能异常、2例肾功能异常和14例电解质异常。22例行头颅影像检查,其中9例额顶叶白质缺血灶、10例脑外间隙增宽、9例脑池扩张、3例苍白球异常信号、5例双侧脑沟增宽、4例脑室旁白质软化可能、髓鞘化落后6例、硬膜下积液3例、脑积水3例、弥漫性脑萎缩2例。19例行基因检测,共检测出20种突变;已见报道17种,分别为c.567dupT、c.609G>A、14号染色体q11.2处缺失0.32Mb区域、c.440-441delGT、c.658-660delAAG、c.656-658delAGA、c.467A>T、c.466C>T、c.323G>A、c.483G>A、c.481C>T、c.16771G>A、c.914T>C、c.682C>T、c.1663G>A、c.*41G>A、c.665C>T,其中c.609G>A是最常见突变;未见报道3种,分别为c.699-700insT、c.1084-10(IVS5)A>G和c.485-487del。大部分患儿被确诊后接受了维生素B12、左卡尼汀、甜菜碱或特殊饮食等治疗。43例患儿中4例失访,3例死亡,34例遗留轻-重度运动及智力发育落后,2例生长发育基本正常。结论甲基丙二酸血症临床表现多样化,以神经系统损伤为著。其化验检查及头颅影像结果无特异性,易出现代谢性酸中毒、高血氨等代谢紊乱及电解质紊乱。基因检测是诊断Objective To summarize the clinical characteristics of children with methylmalonic acidemia(MMA)and analyze the types of genetic mutations in patients for providing a reference in their clinical diagnosis and treatment and improving the understanding of the disease.Methods A total of 43 patients with methylmalonic acid who were treated in the Children’s Hospital of Shanxi Province from January 2013 to December 2019 were collected to retrospectively analyze their clinical data(age of onset,first symptoms,auxiliary examination,genetic results,etc.)and follow-up data.Results The first symptoms of children with MMA were anorexia,poor response and mental retardation in 9 cases,mental and motor retardation in 14 cases,pale complexion in 2 cases,repeated vomiting in 6 cases,dyspnea in 3 cases,and convulsions in 2 cases.There were seven patients without obvious clinical symptoms,and were combined with drowsiness,malnutrition,epilepsy,metabolic acidosis,etc.Laboratory test results showed hyperammonemia in 7 cases,hyperlactic acidemia in 11 cases,anemia in 17 cases,metabolic acidosis in 12 cases,thrombocytopenia in 4 cases,hyperpyruvemia in 7 cases,abnormal myocardial enzymes in 13 cases,abnormal liver function in 9 cases,renal dysfunction in 2 cases,and electrolyte abnormality in 14 cases.There were 22 cases of methylmalonic acidemia undergoing cranial imaging examination,including 9 cases of frontal parietal lobe white matter ischemia,10 cases of extrabrain space widening,9 cases of cistern dilation,3 cases of abnormal globus pallidus,5 cases of bilateral sulcus widening,4 cases of possible ventricular white matter softening,6 cases of myelination lag,3 cases of subdural effusion,3 cases of hydrocephalus,and 2 cases of diffuse cerebral atrophy.There were 19 patients with methylmalonic acidemia undergoing genetic testing,and a total of 20 mutations were detected.Of them,17 types had been reported,including c.567dupT,c.609G>A,0.32Mb region deleted at chromosome 14 q11.2,c.440-441delGT,c.658-660delAAG,c.656-658delAGA,c.46

关 键 词：甲基丙二酸血症 儿童 基因突变 诊治 

分 类 号：R725.8[医药卫生—儿科]