55例青春期起病的甲基丙二酸血症患儿临床特点及随访  

Clinical features and follow-up study on 55 patients with adolescence-onset methylmalonic acidemia

作　　者：马雪 陈哲晖 张会婷 贺薷萱[3] 王峤[4] 丁圆 宋金青[1] 金颖[1] 李梦秋 董慧[1] 张尧[1] 陆妹 陆相朋 曹会茜 王欲琦[7] 陈永兴 郑宏[6] 杨艳玲[1] Ma Xue;Chen Zhehui;Zhang Huiting;He Ruxuan;Wang Qiao;Ding Yuan;Song Jinqing;Jin Ying;Li Mengqiu;Dong Hui;Zhang Yao;Lu Mei;Lu Xiangpeng;Cao Huiqian;Wang Yuqi;Chen Yongxing;Zheng Hong;Yang Yanling(Children′s Medical Center,Peking University First Hospital,Beijing 102600,China;Scientific Research and Innovation Center,Women and Children′s Hospital,Xiamen University,Xiamen 361000,China;DepartmentⅡof Respiratory Medicine,National Clinical Research Center for Respiratory Diseases,Beijing Children′s Hospital,Capital Medical University,Beijing 100045,China;Department of Endocrinology,Genetics and Metabolism,Beijing Children′s Hospital,Capital Medical University,Beijing 100045,China;Department of Pediatrics,Women and Children′s Hospital,Xiamen University,Xiamen 361000,China;Department of Pediatrics,the First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,China;Department of Pediatrics,Baoding Maternal and Child Health Hospital,Baoding 071023,China;Department of Endocrinology,Genetics and Metabolism,Henan Children′s Hospital,Zhengzhou 451161,China)

机构地区：[1]北京大学第一医院儿童医学中心,北京102600 [2]福建省厦门市妇幼保健院(厦门大学附属妇女儿童医院)科研创新中心,厦门361000 [3]首都医科大学附属北京儿童医院国家呼吸疾病临床研究中心临床部二病区,北京100045 [4]首都医科大学附属北京儿童医院内分泌遗传代谢科,北京100045 [5]福建省厦门市妇幼保健院(厦门大学附属妇女儿童医院)儿内科,厦门361000 [6]河南中医药大学第一附属医院儿科,郑州450000 [7]河北省保定市妇幼保健院儿科,保定071023 [8]河南省儿童医院内分泌遗传代谢科,郑州451161

出　　处：《中华儿科杂志》2024年第6期520-525,共6页Chinese Journal of Pediatrics

基　　金：国家重点研发计划(2021YFC2700903,2022YFC2703401)。

摘　　要：目的探讨青春期起病的迟发型甲基丙二酸血症患儿的临床特点、诊断治疗及随访。方法回顾性病例分析。选择2002年1月至2023年6月于北京大学第一医院确诊的青春期起病的55例甲基丙二酸血症患儿为研究对象,收集患儿症状、体征、检验结果、基因变异等临床资料,每3或6个月通过微信、电话或门诊进行随访(截至2023年12月),对患儿的临床表型、基因型及转归进行总结。结果55例患儿中男31例、女24例,于10~18岁发病,中位发病年龄为12岁,第二性征发育均正常,就诊时Tanner 2~5期。9例(16%)在感染后起病,5例(9%)在剧烈运动后起病,从发病到确诊的时间历经2个月至6年。45例(82%)主要表现为神经精神疾病,12例(22%)出现心血管损伤,7例(13%)出现肾脏损伤,12例(22%)合并眼病。54例(98%)患甲基丙二酸血症合并同型半胱氨酸血症,1例患单纯型甲基丙二酸血症(2%)。54例获得了基因诊断,发现20种MMACHC基因变异和2种MMUT基因变异。53例MMACHC基因变异患儿中,1例为PRDX1和MMACHC双基因变异,共105个等位基因变异,前5位高频度变异为39个(37%)c.482G>A、17个(16%)c.609G>A、11个(10%)c.658_660delAAG、10个(10%)c.80A>G、4个(4%)c.567dupT和4个(4%)c.394C>T。所有患儿经过钴胺素、左卡尼汀、甜菜碱和对症治疗后逐渐康复,54例(98%)恢复正常就学和工作。结论青春期起病的甲基丙二酸血症患儿多为合并型,发病隐匿,部分因疲劳或感染诱发疾病,临床识别困难,容易被延误诊断。生化代谢和基因检测是获得正确诊断的关键,通过钴胺素、左卡尼汀和甜菜碱治疗可以显著改善病情。Objective To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia(MMA)and explore preventive strategies.Methods This was a retrospective case analysis of the phenotypes,genotypes and prognoses of adolescence-onset MMA patients.There were 55 patients diagnosed in Peking University First Hospital from January 2002 to June 2023,the data of symptoms,signs,laboratory results,gene variations,and outcomes was collected.The follow-ups were done through WeChat,telephone,or clinic visits every 3 to 6 months.Results Among the 55 patients,31 were males and 24 were females.The age of onset was 12 years old(range 10-18 years old).They visited clinics at Tanner stages 2 to 5 with typical secondary sexual characteristics.Nine cases(16%)were trigged by infection and 5 cases(9%)were triggered by insidious exercises.The period from onset to diagnosis was between 2 months and 6 years.Forty-five cases(82%)had neuropsychiatric symptoms as the main symptoms,followed by cardiovascular symptoms in 12 cases(22%),kidney damage in 7 cases(13%),and eye disease in 12 cases(22%).Fifty-four cases(98%)had the biochemical characteristics of methylmalonic acidemia combined with homocysteinemia,and 1 case(2%)had the isolated methylmalonic acidemia.Genetic diagnosis was obtained in 54 cases,with 20 variants identified in MMACHC gene and 2 in MMUT gene.In 53 children with MMACHC gene mutation,1 case had dual gene variants of PRDX1 and MMACHC,with 105 alleles.The top 5 frequent variants in MMACHC were c.482G>A in 39 alleles(37%),c.609G>A in 17 alleles(16%),c.658_660delAAG in 11 alleles(10%),c.80A>G in 10 alleles(10%),c.567dupT and c.394C>T both are 4 alleles(4%).All patients recovered using cobalamin,L-carnitine,betaine,and symptomatic therapy,and 54 patients(98%)returned to school or work.Conclusions Patients with adolescence-onset MMA may triggered by fatigue or infection.The diagnosis is often delayed due to non-specific symptoms.Metabolic and genetic tests are crucial for a definite diagnosis.Treatment with co

关 键 词：青春期 精神障碍 运动障碍 甲基丙二酸 高同种半胱氨酸血症 

分 类 号：R725[医药卫生—儿科]