Megaloblastic Anemia and Mental Retardation Associated with Hyperfolic-acidemia: Probably due to N5 Methyltetrahydrofolate Transferase Deficiency

A probably new entity of metabolic error of folic acid was described of an infant whose clinical and biochemical characteristics were: 1) mental retarda-tion and a marked dilatation of cerebral ventricles, 2) abnormally high serum L. casei folate activity, 3) abnormally high levels of folate precursor in erythrocytes, and 4) a marked rise in reticulocyte count by an exogenous folate supplementation. The results of investigation on tetrahydrofolate-dependent enzymes of liver specimens revealed a decreased activity of N5 methyltetrahydrofolate transferase of our own patient. It seems therefore likely that an impaired utilization of N5 methyltetrahy-drofolate and its precursor in tissues due to a decreased activity of N5 methyl-tetrahydrofolate transferase led to an abnormal accumulation of N5 methyl-tetrahydrofolate and its precursor in serum and erythrocytes, and that trapping of folate compounds at an N5 methyltetrahydrofolate level caused a functional deficiency of folates with sequence of development of a megaloblastic change in the bone marrow and of an impaired purine biosynthesis of the brain with a marked dilatation of cerebral ventricles.