摘要
目的探讨电子转移黄素蛋白脱氢酶(electron transfer flavoprotein dehydrogenase,ETFDH)基因变异致晚发型戊二酸血症Ⅱ型(glutaric acidemia typeⅡ,GAⅡ)的临床表现及遗传学特点。方法回顾性分析2020年1月首都医科大学附属首都儿童医学中心收治的1例晚发型GAⅡ患者的临床表现及遗传学检测结果,在PubMed、中国知网和万方数据库检索2019—2024年间发表的相关文献,关键词包括“glutaric acidemia typeⅡ”“ETFDH gene”及“戊二酸血症Ⅱ型”“ETFDH基因”,检索策略结合MeSH词汇及自由词进行筛选。总结临床表现。结果患儿男,4月龄,表现为竖头不稳,嗜睡8 d。生后母乳喂养,发育落后,家长体健,否认家族性遗传病及传染病史。患儿对治疗反应差,出现脏器功能障碍、呼吸衰竭。遗传学检测结果提示该患儿ETFDH基因(NM_004453.2)存在Ex.1-Ex.6del以及c.1531G>C(p.D511H)复合杂合变异。根据美国医学遗传学与基因组学学会(American college of medical genetics and genomics,ACMG)指南判断该患者变异位点为疑似致病性变异。文献回顾共检索到11篇文献,共25例18岁以内起病的患者,其中早发型患者6例,4例(66.7%)表现为低血糖或代谢性酸中毒;晚发型患者19例,加上本文报道病例共20例,其中13例(65.0%)表现为肌痛、运动耐力下降或恶心呕吐等症状,5例(25.0%)仅表现为代谢筛查异常,无明显临床表现。包括本例在内的14例中国患者中,共检测到16个ETFDH基因变异位点,c.250G>A为最常见的变异位点,本例患者c.1531G>C突变为首次报道。结论GAⅡ缺乏典型的临床表现,患儿出现不明原因发育迟滞、肌痛、运动障碍、恶心呕吐、代谢异常时,需考虑GAⅡ,遗传学检测可明确诊断。
Objective To explore the clinical and genetic features of late-onset glutaric acidemia typeⅡ(GAⅡ)caused by electron transfer flavoprotein dehydrogenase(ETFDH)gene mutations.Methods A retrospective analysis was conducted on a late-onset GAⅡpatient admitted to the affiliated Capital Center for Children's Health,Capital Medical University.Clinical features and genetic testing results were reviewed.Additionally,related literatures published between 2019 and 2024 were retrieved from PubMed,China National Knowledge Infrastructure(CNKI),and Wanfang databases using keywords such as“glutaric acidemia typeⅡ”“ETFDH gene”.The search strategy combined MeSH terms and free-text words to filter relevant studies.Clinical presentations were then summarized.Results The patient was a 4-month-old male,presenting with upright head instability and drowsiness for 8 days.Breastfeeding after birth,developmental lag,healthy parents,denial of family genetic disease and infectious history.The child had poor response to treatment and developed organ dysfunction and respiratory failure.The results of genetic testing indicated that the ETFDH gene(NM_004453.2)had Ex.1-Ex.6del and c.1531G>C(p.D511H)complex heterozygous variation.The American college of medical genetics and genomics,(ACMG)guidelines determined that the mutation site in this patient was a suspected pathogenic mutation.A total of 11 literatures were reviewed,including 25 patients under 18 years old with onset of the disease,including 6 patients with early-onset,and 4 patients(66.7%)showed hypoglycemia or metabolic acidosis.There were 19 late-onset patients,and including the case reported in this article,there were a total of 20 cases,13 patients(65.0%)showed myalgia,decreased exercise endurance or nausea and vomiting,and 5 patients(25.0%)showed only abnormal metabolic screening without obvious clinical manifestations.In 14 Chinese patients,including this case,a total of 16 ETFDH gene mutation sites were detected,c.250G>A was the most common mutation site,and c.1531G>C mutation in this case was reported for the first time.Conclusions GAⅡlacks typical clinical features.When children present with unexplained developmental delay,myalgia,motor disorders,nausea,vomiting,or metabolic abnormalities,GAⅡshould be considered.Genetic testing can be a clear diagnosis.
作者
程沛迪
吴凡
申梦瑶
沈梦晓
郑萍
吴欢欢
谢丽娜
陈倩
Cheng Peidi;Wu Fan;Shen Mengyao;Shen Mengxiao;Zheng Ping;Wu Huanhuan;Xie Lina;Chen Qian(Department of Neurology,Capital Center for Children's Health,Capital Medical University,Beijing 100020,China;Graduate School of Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100005,China)
出处
《中国医学前沿杂志(电子版)》
北大核心
2025年第6期63-69,共7页
Chinese Journal of the Frontiers of Medical Science(Electronic Version)
基金
国家重点研发项目(2022YFC2703903)
吴阶平医学基金会临床科研专项(320.6750.2021-04-33)
北京亦城合作发展基金会科研项目罕见病相关课题资助公益项目(YCXJ-JZ-2023-017)。
