Eight cases of hereditary hyperhomocysteinemia with neurological involvement: clinical and genetic analysis
10.3760/cma.j.cn113694-20240811-00542
- VernacularTitle: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
- Author:
Xianru CHENG
1
;
Xinghua LUAN
;
Jingjiong CHEN
;
Bo XUE
;
Wenzheng WANG
;
Hui WEN
;
Xiuzhe WANG
;
Li CAO
;
Wotu TIAN
Author Information
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
- Publication Type:Journal Article
- Keywords:
Hyperhomocysteinemia;
Folic acid;
Vitamin B12;
Carnitine;
Methylmalonic acid
- From:
Chinese Journal of Neurology
2025;58(1):64-75
- CountryChina
- Language:Chinese
-
Abstract:
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 (38.4-190.6 μmol/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.
