目的 探讨以婴儿期脑积水为突出表现的亚甲基四氢叶酸还原酶缺乏症患儿的临床特点、治疗及预后。方法 2例患儿因脑积水于北京大学第一医院儿科就诊，经血清总同型半胱氨酸、血液氨基酸及酰基肉碱谱、尿有机酸和基因分析确诊，对患儿的临床特点、代谢异常、MTHFR基因变异、诊断、治疗及预后等进行回顾性研究。结果 2例患儿为男童，分别于2月龄及4月龄起病，以脑积水及癫痫发作为主要表现，血清总同型半胱氨酸显著增高，血甲硫氨酸降低或处于正常低值，尿有机酸正常，头颅影像检查发现严重脑积水。两患儿服用甜菜碱、亚叶酸钙、钴胺素等治疗后血清总同型半胱氨酸下降，侧脑室腹腔分流手术后颅压改善，但智力运动发育明显迟缓，仍有癫痫发作。两患儿MTHFR基因均存在复合杂合变异，确诊为亚甲基四氢叶酸还原酶缺乏症所致同型半胱氨酸血症2型。4种变异中1种为已知致病变异，3种为未报道的新变异。结论 亚甲基四氢叶酸还原酶缺乏症患儿可于婴儿早期发生脑积水及癫痫等严重神经系统疾病，血清总同型半胱氨酸及基因检测是早期诊断的关键。

Objective To investigate the clinical characteristics, treatment, and prognosis of hydrocephalus due to methylenetetrahydrofolate reductase (MTHFR) deficiency caused by MTHFR gene variations. Methods Two boys admitted to the Department of Pediatrics of Peking University First Hospital with hydrocephalus were diagnosed by serum total homocysteine, blood amino acid and acylcarnitine profile, urinary organic acid, and genetic analysis. The clinical manifestations, biochemical features, MTHFR gene variants, diagnosis, therapy, and prognosis were retrospectively analyzed. Results Two children presented with hydrocephalus and seizures at 2 and 4 months of age, respectively, with significantly increased serum total homocysteine, reduced or low normal blood methionine, normal urinary organic acids, and severe hydrocephalus on cranial imaging. Serum total homocysteine decreased after treatment with betaine, calcium folinic acid, and cobalamin in both children, and intracranial pressure improved after lateral ventriculoperitoneal shunt surgery, but intellectual and motor development was delayed and seizures were still present. The diagnosis of homocysteinemia type 2 due to MTHFR deficiency was confirmed by the presence of compound heterozygous variants in the MTHFR gene in both children. One of the 4 variants was a known pathogenic variant and 3 were unreported novel variants. Conclusion Children with MTHFR deficiency may develop severe neurological symptoms such as hydrocephalus and epilepsy in early infancy, and serum total homocysteine and gene analysis are keys for the diagnosis.