MT-ATP6基因9176T>C变异致晚发型Leigh综合征一家系报道并文献复习

MT-ATP6gene9176T>C mutation leading to late-onset leigh syndrome:a family report and literature review

目的探讨晚发型Leigh综合征(leigh syndrome,LS)的临床、头部MRI和MT-ATP6基因变异特点。方法详细收集一家系中2例晚发型Leigh综合征患者的临床资料、脑影像以及基因检测结果,并结合文献进行讨论。结果先证者,男,9岁,以“双侧眼睑下垂、步态不稳半年,精神行为异常4个月”为主诉,于2020年4月10日就诊于河南省焦作市人民医院。患儿出生正常,自幼体质和智力均较同龄人差。半年前出现双侧眼睑下垂,视物有重影,并逐渐出现步态不稳,跑步困难,头部MRI检查提示双侧基底节区和脑干异常信号。4个月前无诱因出现间断性恶心呕吐,精神行为异常。2个月前感冒发热后突发昏迷抽搐,在当地医院抢救治疗,生命体征平稳后转入河南省焦作市人民医院。查体:身材矮小,体型消瘦,呈睁眼昏迷状。双侧眼睑下垂遮盖瞳孔大于1/2,双眼球居中固定,吞咽障碍,鼻饲管饮食。四肢肌张力高,腱反射活跃,肢体呈屈曲状,双侧病理征阳性。家族史:患儿父母非近亲结婚,父亲身体健康,母亲身材矮小,有精神行为异常病史。先证者的哥哥,14岁,发育均较同龄人差。7岁出现眼睑下垂,步态不稳,无昏迷抽搐病史。先证者和其哥哥行骨骼肌病理活检未见破碎红边纤维,线粒体基因组检测均发现有MT-ATP6基因9176T>C变异。结论晚发型Leigh综合征临床表型具有较大的异质性,可伴有精神行为异常和认知障碍。头部MRI以双侧基底节和中脑导水管周围异常信号为其影像特点,基因检测是诊断Leigh综合征的重要依据。

Objective To investigate the clinical,brain MRI and MT-ATP6 gene variation characteristics of late-onset Leigh syndrome(LS).Methods The clinical data,brain imaging and genetic test results of two patients with late-onset Leigh syndrome in a family were collected in detail,and discussed in combination with the literature.Results The proband,male,9 years old,complained of"bilateral ptosis,unstable walking for half a year,abnormal mental behavior for 4 months".He was admitted to our hospital on April 10,2020.Patient was born normally,his physique and intelligence was worse that of his peers since childhood.Six months ago,the patient had bilateral ptosis and double vision,and he gradually developed unstable walking and difficulty in running.Brain MRI examination showed abnormal signals in bilateral basal ganglia and brain stem.4 months ago,he had intermittent nausea and vomiting,abnormal mental behavior without any inducement.Two months ago,he suddenly fell into a coma and twitched after catching a cold and fever.He was rescued and treated in a local hospital.His vital signs were stable and transferred to our hospital.Physical examination:short stature,thin physique,coma with eyes open.Bilateral ptosis covers more than half of the pupil,bilateral eyeball center fixation,dysphagia,nasal feeding diet.Muscle tension in the limbs was high,tendon reflex was active,and the limbs were flexing,Bilateral pathological signs were positive.Family history:the child’s parents are not consanguineous marriage,the father is in good health,the mother is short and has a history of mental and behavioral abnormalities.The proband’s brother,14 years old,was less developed than his peers.At the age of 7,he developed ptosis,unstable walking and no history of coma and convulsions.No ragged red fibers were found in skeletal muscle pathological biopsies of the proband and his brother.The mutation of MT-ATP6 gene 9176T>C was found by mitochondrial genome detection.Conclusions The clinical phenotype of late-onset Leigh syndrome is heterogeneous,which may be accompanied by mental and behavioral abnormalities and cognitive impairment.Brain MRI is characterized by abnormal signals in bilateral basal ganglia and midbrain periaqueductal region.Gene detection is an important basis for the diagnosis of Leigh syndrome.