论文部分内容阅读
目的:探讨n SERAC1基因变异所致MEGDHEL综合征的临床特征及遗传学特点。n 方法:回顾性总结1例2016年8月转入复旦大学附属儿科医院并诊断为MEGDHEL综合征患儿的临床和分子生物学特征，并通过文献复习，分析和总结国内外已报道的MEGDHEL综合征病例的临床特征及遗传学特点。结果:（1）病例：患儿男，生后2 d因高乳酸血症转入本院。体格检查发现皮肤散在瘀斑。实验室检查示凝血功能障碍；头颅MRI示双侧基底节异常信号；检测到n SERAC1基因c.442C>T(p.Arg148*)纯合变异，为人类基因突变数据库收录的致病变异位点，父母均为杂合携带者，诊断为MEGDHEL综合征。随访至3岁11月龄，患儿存在精神运动发育迟缓、肢体痉挛、肌张力障碍、感音性耳聋、丧失语言能力。（2）文献复习：共检索到87例病例，合并本例共88例，共涉及57种不同变异位点。临床表现具有同质性，多在新生儿期起病（72%，62/86），以严重可逆性肝功能异常（49%，38/77）、新生儿低血糖（44%，35/80）为主；婴幼儿期开始出现一系列神经系统受累表现，常见肌张力低下（86%，68/79）、肢体进行性痉挛（82%，67/82）、肌张力障碍（80%，66/82）、智力障碍（88%，58/66）和感音性耳聋（74%，59/80）；头颅MRI提示双侧基底节受累（93%，70/75）；3-甲基戊烯二酸尿（98%，80/82）。目前主要采取支持治疗，预后极差。n 结论:新生儿期表现为不明原因可逆性肝功能异常或低血糖等异常，婴幼儿期逐渐出现进行性耳聋-肌张力障碍综合征的患儿，应高度怀疑MEGDHEL综合征，此类患儿多数预后不良，新生儿期经基因检测可早期诊断。“,”Objective:To investigate the clinical and genetic features of 3-methylglutaconic aciduria, dystonia-deafness, hepatopathy, encephalopathy, Leigh-like syndrome(MEGDHEL syndrome) caused by n SERAC1 gene variation.n Methods:This study retrospectively described the clinical and molecular features and prognosis of a baby boy who was transferred to Children's Hospital of Fudan University and later diagnosed with MEGDHEL syndrome in August 2016. A summary of the clinical and genetic manifestations of MEGDHEL syndrome cases reported in China and foreign areas was conducted through a literature review.Results:(1) Case report: The 2-day-old patient was transferred to Children's Hospital of Fudan University due to hyperlactic acidemia after birth. Physical examination revealed scattered petechiae and ecchymoses of the skin. Laboratory examination showed coagulation disorders and cranial MRI revealed abnormal signals in both basal ganglia. A homozygous variation of c.442C>T(p.Arg148*) in then SERAC1 gene was detected in the patient, which is a pathogenic variant included in the Human Gene Mutation Database. Both of his parents were heterozygous carriers, thereby the diagnosis of MEGDHEL syndrome was confirmed. Followed up to the age of three years and 11 months, he was found to have psychomotor retardation, spasticity, dystonia, deafness, and loss of language ability. (2)Literature review: Together with the case reported in this study, a total of 88 cases were retrieved, involving 57 different variants. The clinical features were homogenous, with onset mostly in the neonatal period (72%, 62/86), and severe reversible liver dysfunction (49%, 38/77) and neonatal hypoglycemia (44%, 35/80) were the main features. Nervous system was affected since infancy and common symptoms, included hypotonia (86%, 68/79), progressive spasticity (82%, 67/82), dystonia (80%, 66/82), intellectual disability (88%, 58/66) and sensorineural hearing impairment (74%, 59/80). Furthermore, bilateral basal ganglia involvement on cranial MRI (93%,70/75) and 3-methylglutaconic aciduria (98%,80/82) were also seen. Supportive care is currently the main management, however, the prognosis is extremely poor.n Conclusions:MEGDHEL syndrome should be highly suspected when reversible neonatal liver dysfunction or hypoglycemia of unknown reasons in neonatal period, followed by progressive deafness-dystonia syndrome in infancy. As the prognosis of these patients is usually poor, genetic testing may provide an early diagnosis in neonatal period.