摘要目的 分析线粒体DNA耗竭综合征(MDS)患儿的临床表型及基因型特点.方法 回顾性总结分析2010年10月至2018年4月首都医科大学附属北京儿童医院神经内科确诊的12例MDS患儿(男8例,女4例)的临床表现及基因检查结果.结果 12例MDS患儿起病前发育正常或落后,起病年龄为0～2.9岁,多为生后发病或感染后起病,首发症状为喂养困难、抽搐、肌无力、发育倒退或肝功能损害,所有患儿均出现发育迟缓、喂养困难、肌无力、吞咽困难,部分患儿逐渐出现消瘦(9例)、听力损害(7例)、眼睑下垂(6例)、抽搐(5例)、呼吸困难(4例)、视力损害(1例)、多毛(1例)、血乳酸升高(7例)、肝酶升高(4例)、心肌酶升高(2例)、脑脊液蛋白升高(3例)、血尿代谢筛查异常(10例)、头颅磁共振成像异常(10例)、肌电图示神经源性或肌源性损害(5例).至2018年4月末次随访5例患儿因感染、全身器官功能衰竭死亡.脑肌病型6例,SUCLG1基因变异3例(其中c.916G＞T,c.619T＞C和c.980dupT为新变异);SUCLA2基因变异2例(其中c.851G＞A,c.971G＞A为新变异);RRM2B基因变异1例(其中c.456-2A＞G,c.212T＞C为新变异).肝性脑病型3例均为POLG基因变异(其中c.3151G＞A,c.2294C＞T,c.2858G＞C,c.680G＞A,c.150_158delGCAGCAGCA为新变异),婴儿起病的脊髓小脑共济失调型2例,均为TWNK基因变异(其中c.1163C＞T,c.1319T＞C,c.257_258delAG,c.1388G＞A为新变异),肌病型1例为TK2基因变异(其中c.557C＞G,c.341A＞T为新变异).结论 儿童MDS临床表型及基因变异谱异质性强,本组共发现MDS 6种致病基因的18个新变异,丰富了中国儿童MDS的临床表型及基因型.

abstractsObjective To explore the phenotype and genotype of mitochondrial DNA depletion syndromes (MDS) in Chinese children.Methods The clinical and genetic data of 12 MDS patients (8 were boys and 4 were girls) diagnosed in the Department of Neurology in Beijing Children's Hospital,Capital Medical University from October 2010 to April 2018 were retrospectively collected and analyzed.Results The developmental milestones were normal or mildly retardated before disease onset.The age of onset ranged from 0 to 2.9-year-old.Most cases developed postnatal or after infection.The most common initial symptoms were feeding difficulty,seizure,muscle weakness,psychomotor regression and hepatic dysfunction.At the last evaluation,all the patients had developmental retardation,failure to thrive,muscle weakness,and dysphagia.Other clinical features were weight loss (9 cases),hearing impairment (7 cases),ptosis (6 cases),seizure (5 cases),dyspnea (4 cases),visual impairment (1 case),hirsutism (1 case),lactic acidosis (7 cases),elevated hepatic enzymes (4 cases) and creatine kinase (2 cases),elevated protein in cerebrospinal fluid (3 cases),abnormalities on screening for inborn error of metabolism (10 cases) and brain magnetic resonance imaging (MRI) (10 cases),abnormal electromyogram (including neurogenic or myogenic injury) (5 cases).Five patients died of infection or multiple organ failure.A total of 18 novel mutations presented below were detected in these patients.Among the 6 cases of encephalomyopathy,there were 3 with SUCLG1 mutation (c.916G＞T,c.619T＞C,c.980dupT were novel),2 with SUCLA2 mutation (c.851G＞A,c.971G＞A were novel),and one with RRM2B mutation (c.456-2A＞G,c.212T＞C were novel).All the cases of hepatic encephalopathy all had POLG mutations (c.3151G＞A,c.2294C＞T,c.2858G＞C,c.680G＞A and c.150_158delGCAGCAGCA were novel).Two cases of infantile-onset spinocerebellar ataxia had TWNK mutations (c.1163C＞T,c.1319T＞C,c.1388G＞A and e.257_258delAG were novel).One case of myopathy had TK2 mutations (c.557C＞G and c.341A＞T were novel).Conclusions The clinical and genetic features of MDS were heterogeneous.Eighteen novel mutations in six MDS related genes were reported,which expanded the genetic spectrum of MDS in Chinese children.