Abstract: Objective　To explore the clinical characteristics, treatment and prognosis of methylenetetrahydrofolate reductase deficiency caused by MTHFR gene mutation. Methods　The clinical data and MTHFR gene test results in one child with epilepsy and hydrocephalus caused by MTHFR deficiency were retrospectively analyzed, and the related literature were reviewed. Results　Convulsions, irregular breathing, feeding difficulties, hypotonia and elevated homocysteine levels (147.9 μmol/L) were observed on the 10th day after birth in a female infant. Gene sequencing showed that there were compound heterozygous mutations in MTHFR gene (c.1319_c.1320 insTT and c.1262G>A) and the mutation c.1319_c.1320 insTT was first reported. After 2 weeks of treatment with betaine, calcium folate, vitamin B6 and vitamin B12, the serum total homocysteine level was decreased and the clinical symptoms were improved, but apparent hydrocephalus and mental retardation happened within the next one month. Conclusion　Early onset methylenetetrahydrofolate reductase deficiency can be manifested in the early postnatal period. Blood homocysteine determination and gene detection are helpful for early diagnosis and intervention.