Abstract:

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.

Key words: hydrocephalus, methylenetetrahydrofolate reductase, homocysteinemia, MTHFR gene