Tohoku J. Exp. Med., 1967, 93

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

TSUNEO ARAKAWA, KUNIAKI NARISAWA, KANEO TANNO, KAZUO OHARA, OTOTAKA HIGASHI, YOSHIYUKI HONDA, TSUNENOBU TAMURA, YOSHIRO WADA, TAKASHI MIZUNO, TADASHI HAYASHI, YUTAKA HIROOKA,^* TADASHI OHNO^* and MORIJI IKEDA^*

Department of Pediatrics (Prof. Ts. Arakawa), Faculty of Medicine, Tohoku University, Sendai
^*Pediatric Clinic (Chief: Dr. Y. Hirooka), Akita Prefectural Central Hospital, Akita

A probably new entity of metabolic error of folic acid was described of an infant whose clinical and biochemical characteristics were: 1) mental retardation 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 methyltetrahydrofolate and its precursor in tissues due to a decreased activity of N⁵ methyltetrahydrofolate transferase led to an abnormal accumulation of N⁵ methyltetrahydrofolate 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.

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Tohoku J. Exp. Med., 1967, 93, 1-22