Hydrocephalus internus in two patients with 5,10-methylenetetrahydrofolate reductase deficiency

Abstract

Hydrocephalus internus (HCI) of all four ventricles in association with early neurological abnormalities is described as the presenting symptom in two patients with 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency. Decreased activity of MTHFR leads to reduction of 5-methyltetrahydrofolate, the main methyl donor for methionine synthesis necessary for synthesis of S-adenosyl-methionine (SAM). Demyelination in MTHFR deficiency has been attributed to low SAM levels in the brain. The biochemical hallmarks of the disorder are hyperhomocystinemia, homocystinuria and low levels of plasma methionine. Hydrocephalus internus requiring neurosurgical intervention has to our knowledge not been reported as a presenting feature of homocystinuria due to deficiency of MTHFR so far. The surprising finding of HCI of all four ventricles in MTHFR deficiency must be kept in mind when evaluating patients with hydrocephalus of unknown origin.