以神经系统受累为主的8例遗传性高同型半胱氨酸血症患者临床与遗传学分析  

Eight cases of hereditary hyperhomocysteinemia with neurological involvement:clinical and genetic analysis

作　　者：程先茹 栾兴华 陈静炯 薛波 王文政[3] 闻晖[3] 王修哲 曹立 田沃土 Cheng Xianru;Luan Xinghua;Chen Jingjiong;Xue Bo;Wang Wenzheng;Wen Hui;Wang Xiuzhe;Cao Li;Tian Wotu(Department of Neurology,Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,Shanghai Neurological Rare Disease Biobank and Precision Diagnostic Technical Service Platform,Shanghai 200233,China;Suzhou Hospital of Anhui Medical University,Suzhou 234000,China;Department of Psychiatry,Shanghai Mental Health Center,Shanghai 200030,China)

机构地区：[1]上海交通大学医学院附属第六人民医院神经内科,上海市神经系统罕见疾病生物样本库和精准诊断专业技术服务平台(筹),上海200233 [2]安徽医科大学附属宿州医院神经内科,宿州234000 [3]上海市精神卫生中心精神科,上海200030

出　　处：《中华神经科杂志》2025年第1期64-75,共12页Chinese Journal of Neurology

基　　金：国家自然科学基金(82201398,82071258);上海市优秀学术带头人(23XD1402500);上海浦江人才计划(22PJD052);上海市第六人民医院基础科研青年学者培育项目(YNQN202224)。

摘　　要：目的探讨以神经系统症状为主要临床特点的遗传性高同型半胱氨酸血症的临床特征及表型与基因型特点。方法收集2020年9月至2023年12月上海交通大学医学院附属第六人民医院神经内科收治的8例高同型半胱氨酸血症患者的临床资料、体格检查、影像学检查、血-尿串联质谱分析和基因检测结果等,对其临床、遗传、发病机制进行总结分析。结果在8例患者中,男女比例为5∶3,发病年龄7~74(40.4±7.4)岁。7例为成年期起病,1例为儿童期起病,起病症状各异,如进行性双下肢僵硬行走困难、肢体麻木、震颤、精神行为异常、脑血管事件等。初诊时,8例患者均存在中-重度的高同型半胱氨酸血症(达38.4~190.6μmol/L)。接受头颅影像学检查的5例患者均存在脑白质病变。基因检测结果提示其中7例患者为MTHFR基因致病性变异(1例为c.416C>T、6例为c.665C>T)、1例为MMACHC基因致病性变异(c.482G>A)。结论遗传性高同型半胱氨酸血症属于代谢性疾病,其临床表型复杂、轻重不一、致病基因多样,以神经系统受累为主要临床特点的病例并不少见,如痉挛性截瘫样表现、震颤、周围神经病、精神行为异常、脑血管病。Objective To investigate the clinical,phenotypic and genotypic features of hereditary hyperhomocysteinemia mainly involving the nervous system.Methods The clinical data,physical examination,imaging results,blood-urine tandem mass spectrometry analysis and genetic results of 8 patients with hyperhomocysteinemia from the Department of Neurology of the Shanghai Sixth People′s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from September 2020 to December 2023 were collected,and the clinical,genetic features and pathogenic mechanisms of these patients were summarized and analyzed.Results Among all the 8 patients(male∶female=5∶3),the age of onset was 7 to 74(40.4±7.4)years.Seven had adult-onset and 1 had juvenile-onset,with various types of onset symptoms,including progressive stiffness in lower limbs and walking difficulty,limb numbness,tremor,mental and behavioral abnormalities,cerebrovascular events,etc.Moderate to severe hyperhomocysteine(38.4-190.6μmol/L)was present in all patients at first diagnosis.Among the 5 patients with cranial imaging examinations,all had white matter lesions.The genetic testing showed 7 patients with MTHFR gene pathogenic mutations(1 case with c.416C>T,and 6 cases with c.665C>T),and 1 patient with MMACHC gene pathogenic mutation(c.482G>A).Conclusions Hereditary hyperhomocysteinemia is a metabolic disease,with complicated manifestations,varying degrees of severity,and diverse pathogenic genes.The cases with neurological involvement are not rare,such as spastic paraplegia-like manifestations,tremor,peripheral neuropathy,mental and behavioral abnormalities,cerebrovascular events.

关 键 词：高同种半胱氨酸血症 叶酸 维生素B12 肉碱 甲基丙二酸 

分 类 号：R741[医药卫生—神经病学与精神病学]