Objective: To explore the diagnosis and treatment of adolescence-onset methylenetetrahydrofolate reductase (MTHFR) deficiency. Methods: This was a retrospective case study. Nine patients with adolescence-onset MTHFR deficiency were diagnosed at Peking University First Hospital from January 2016 to December 2022, and followed up for more than 1 year. Their general information, clinical manifestations, laboratory tests, cranial images, MTHFR gene variants, diagnosis, treatment, and outcome were analyzed retrospectively. Results: The 9 patients came from 8 families. They had symptoms at age of 8.0 years to 17.0 years and diagnosed at 9.0 years to 17.5 years. Eight were male and 1 was female. Two patients were brothers, the elder brother developed abnormal gait at 17.0 years; and the younger brother was then diagnosed at 15.0 years of age and treated at the asymptomatic stage, who was 18.0 years old with normal condition during this study. The main manifestations of the 8 symptomatic patients included progressive dyskinesia and spastic paralysis of the lower limbs, with or without intellectual decline, cognitive impairment and behavioral abnormalities. Totally, 15 variants of MTHFR gene were identified in the 9 patients, including 8 novel variants. Five patients had brain image abnormalities. Increased plasma total homocysteine level (65-221 μmol/L) was found in all patients, and decreased to 20-70 μmol/L after treatment with betaine and calcium folinate. Besides, the 8 symptomatic patients had their behavior and cognitive problems significantly improved, with a legacy of lower limb motor disorders. Conclusions: Late-onset MTHFR deficiency can occur in adolescence. The diagnosis is usually delayed because of non-specific clinical symptoms. The test of blood total homocysteine could be used as a selective screening test. Eight novel varients of MTHFR gene were identified. Timely treatment can improve clinical condition significantly, and pre-symptomatic treatment may prevent brain damage.
目的： 探讨青春期发病的亚甲基四氢叶酸还原酶（MTHFR）缺乏症的诊断和治疗策略。 方法： 回顾性病例分析。以2016年1月至2022年12月于北京大学第一医院确诊并随访1年以上的9例青春期发病的MTHFR缺乏症患儿为研究对象，总结患儿的临床表现、生化代谢特点、头颅影像学异常、MTHFR基因变异、诊断、治疗及转归。 结果： 9例患儿来自8个家庭，男8例、女1例，发病年龄8.0~17.0岁，确诊年龄9.0~17.5岁。其中2例为同胞兄弟，兄长17.0岁时出现步态异常，弟弟15.0岁时诊断并开始治疗，截至18.0岁尚无症状。8例有症状患儿的主要表现为进行性运动障碍，下肢痉挛性瘫痪，伴或不伴智力倒退、认知障碍及行为异常。9例患儿共检出15种MTHFR基因变异，其中8种为新变异。5例患儿存在头颅影像学异常。所有患儿血清总同型半胱氨酸中重度升高（65~221 μmol/L），予甜菜碱、亚叶酸钙治疗后明显下降（20~70 μmol/L），精神行为及认知问题均显著好转，8例患儿遗留下肢运动障碍。 结论： 晚发型MTHFR缺乏症可在青春期发病，临床缺乏特异性，易被延误诊断，血清总同型半胱氨酸测定经济方便，应作为筛查技术。发现8种MTHFR基因新变异，患儿治疗后病情显著改善，症状前治疗可预防脑损伤。.