Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare autosomal recessive genetic disorder caused by mutations in the MTHFR gene, leading to a variety of clinical manifestations. In October 2022, the Second Xiangya Hospital of Central South University admitted a 21-year-old male patient with neuropsychiatric disorders, presenting primarily with cognitive decline, limb tremors, abnormal mental and behavioral symptoms, seizures, and gait disturbances. These symptoms had gradually developed over 5 years, worsening significantly in the past year. The patient's plasma homocysteine levels were 10 times higher than normal, and brain MRI revealed brain atrophy and significant abnormal signals in the bilateral paraventricular nuclei and heads of the bilateral caudate nuclei. Further genetic testing identified a paternal mutation c.1604G>A (p.R535Q) and a maternal mutation c.227T>G (p.L76R) of the MTHFR gene. After betaine supplementation, the plasma homocysteine levels decreased within a week, and the symptoms improved. The patient was ultimately diagnosed with severe hyperhomocysteinemia due to MTHFR deficiency. The c.227T>G (p.L76R) mutation represents a novel missense mutation in the MTHFR gene associated with MTHFR deficiency, but further research is needed to confirm its potential pathogenicity. Early treatment with betaine can fully reverse the symptoms.
亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase，MTHFR)缺乏症是一种罕见的常染色体隐性遗传疾病，由MTHFR基因突变引起，具有多种临床表现。中南大学湘雅二医院于2022年10月收治1例21岁男性患者，患有神经精神障碍，主要表现为认知能力下降、肢体震颤、精神和行为异常、癫痫发作、步态障碍，这些症状在5年内逐渐发展，并在最近1年中恶化。患者的血浆同型半胱氨酸(homocysteine，HCY)明显高于正常水平的10倍，脑MRI显示脑萎缩，双侧室旁核和双侧尾状核头部有明显异常信号，通过进一步的基因检测鉴定出MTHFR基因的父系突变c.1604G>A(p.R535Q)和母系突变c.227T>G(p.L76R)。补充甜菜碱1周后，患者血浆HCY下降，症状改善。患者最终诊断为MTHFR缺乏引起的严重高同型半胱氨酸血症。c.227T>G(p.L76R)是MTHFR基因相关MTHFR缺乏症的一种新的错义突变，但需要更多的研究来证实其可能的致病性。经过早期甜菜碱治疗后该病可完全逆转。.
亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase，MTHFR)缺乏症是一种罕见的常染色体隐性遗传疾病，由MTHFR基因突变引起，具有多种临床表现。中南大学湘雅二医院于2022年10月收治1例21岁男性患者，患有神经精神障碍，主要表现为认知能力下降、肢体震颤、精神和行为异常、癫痫发作、步态障碍，这些症状在5年内逐渐发展，并在最近1年中恶化。患者的血浆同型半胱氨酸(homocysteine，HCY)明显高于正常水平的10倍，脑MRI显示脑萎缩，双侧室旁核和双侧尾状核头部有明显异常信号，通过进一步的基因检测鉴定出MTHFR基因的父系突变c.1604G>A(p.R535Q)和母系突变c.227T>G(p.L76R)。补充甜菜碱1周后，患者血浆HCY下降，症状改善。患者最终诊断为MTHFR缺乏引起的严重高同型半胱氨酸血症。c.227T>G(p.L76R)是MTHFR基因相关MTHFR缺乏症的一种新的错义突变，但需要更多的研究来证实其可能的致病性。经过早期甜菜碱治疗后该病可完全逆转。
Keywords: MTHFR gene; genetic metabolism; hyperhomocysteinemia; methylenetetrahydrofolate reductase deficiency; neuropsychiatric disorders; new mutation.