Methylenetetrahydrofolate reductase deficiency: Importance of early diagnosis

Methylenetetrahydrofolate reductase deficiency is the most common inborn er ror of folate metabolism and should be suspected when homocystinuria is com bined with hypomethioninemia. The main clinical findings are neurologic sig ns such as severe developmental delay, marked hypotonia, seizures, microcep haly, apnea, and coma. Most patients present in early life. The infantile f orm is severe, with rapid deterioration leading to death usually within 1 y ear. Treatment with betaine has been shown to be efficient in lowering homo cysteine concentrations and returning methionine to normal, but the clinica l response is variable. We report two brothers with methylenetetrahydrofola te reductase deficiency: the first was undiagnosed and died at 8 months of age from neurologic deterioration and apnea, while his brother, who was tre ated with betaine from the age of 4 months, is now 3 years old and has deve lopmental delay.