NDUFAF5基因变异致线粒体复合物Ⅰ缺陷2例并文献复习

Mitochondrial complex Ⅰ deficiency due to NDUFAF5 gene mutations: report of 2 cases and literature review

目的探讨NDUFAF5基因变异所致线粒体复合物Ⅰ缺陷临床表型特点及基因型。方法回顾并随访2015年2月至2018年7月北京大学第一医院儿科就诊的2例NDUFAF5基因变异患儿临床资料。以"NDUFAF5"为检索词检索PubMed数据库、万方、中国期刊全文和中国维普数据库(1975年1月至2020年2月)文献报道病例,总结临床表型及基因型。结果病例1于1岁4个月感染后出现智力运动倒退,末次随访至5岁6个月病情未再反复。头颅磁共振成像(MRI)示额顶颞叶白质、基底核区、丘脑、小脑、脑干、胼胝体多发病变。例2于7岁4个月以急性视神经病起病,末次随访至8岁8个月,视力好转,无其他症状。头颅MRI示中脑大脑脚、导水管周围、延髓、壳核病变,脊髓MRI示颈1-4椎体水平长节段脊髓病变。2例患儿均检测到NDUFAF5基因双等位基因变异,例1为c.764C>T(p.Ala255Val)/c.508C>T(p.Arg170Trp),例2为c.836T>G(p.Met279Arg)纯合变异。符合检索条件的6篇文献共报道14例患者,常见临床表型为Leigh综合征。新生儿期起病2例,病情进展迅速,1岁内死亡。婴幼儿期起病11例,72.7%(8/11例)起病前智力、运动发育正常,常见首发症状为发育倒退、喂养困难、肌张力障碍,72.7%(8/11例)为感染后急性/亚急性起病,发作性加重,幼儿期或儿童期死亡。儿童期1例以肌张力障碍起病,至成年期出现双眼视力障碍。结论NDUFAF5基因变异发病年龄范围广,临床表型存在较大差异,临床表型主要为Leigh综合征。常见婴幼儿期起病,多呈感染后发作性加重病程。少见儿童期起病。

Objective To analyze the clinical features and genotypes of mitochondrial complexⅠdeficiency due to NDUFAF5 gene mutations.Methods Clinical data of 2 cases with mitochondrial complexⅠdeficiency due to NDUFAF5 gene mutations admitted in the Department of Pediatrics,Peking University First Hospital from February 2015 to July 2018 were retrospectively reviewed and followed up.Reported cases of mitochondrial complexⅠdeficiency due to NDUFAF5 gene mutations were searched in online databases,including the PubMed,Wanfang,Chinese Journal Full-Text Database and VIP database from January 1975 to February 2020 with"NDUFAF5"as the key word.Through literature review,clinical features and genotypes of mitochondrial complexⅠdeficiency due to NDUFAF5 gene mutations were summarized.Results Case 1 showed mentor and mental regression after infection at the age of 1 year and 4 months.The condition of case 1 remained stable at the age of 5 year and 6 months at the last follow-up.Brain magnetic resonance imaging(MRI)showed multiple lesions in the white matter of the frontal and parieto-occipital lobes,basal ganglia,thalamus,cerebellum,brain stem and corpus callosum.Case 2 showed rapidly bilateral visual impairment at the age of 7 years and 4 months.The patient′s vision moderately recovered at the age of 8 years and 8 months.Brain MRI showed midbrain,periaqueductal gray,medulla oblongata and putamen lesions.Spinal MRI showed continuous lesions in the cervical cord 1-4.Genetic test showed NDUFAF5 gene c.764C>T(p.Ala255Val)and c.508C>T(p.Arg170Trp),homozygous c.836T>G(p.Met279Arg)mutations in case 1 and case 2 respectively.Through online searching,6 reports involving 14 cases were retrieved.The most common clinical phenotype was Leigh syndrome.Two cases had disease onset during the neonatal period,and their disease progressed rapidly and died within 1 year old.Eleven cases had onset during the infantile period,and 72.7%(8/11 cases)of them had a normal development.The common initial symptoms were mental or motor regression,feeding difficulty and dystonia.Seventy-two point seven percent(8/11 cases)had acute/subacute onset after infection,showing paroxysmal deterioration,and died in infancy or childhood.One patient developed dystonia in childhood and visual impairment in adulthood.Conclusions The onset age ranged from neonatal period to childhood in patients with NDUFAF5 gene mutations,and their clinical phenotypes vary a lot.The main clinical phenotype is Leigh syndrome.Disease onset during the infantile period is frequent,and mostly presents paroxysmal deterioration after infection,while disease onset in childhood is rare.