Vitamin B6 Dependent Xanthurenic Aciduria

Abstract

Two children (siblings) with mental retardation revealed an excessive output of xanthurenic acid, kynurenic acid, 3-hydroxykynu-renine and kynurenine in urine following tryptophan loading. The disturbance was normalized temporarily by treatment with large doses of vitamin B6. The levels of pyridoxal phosphate in sera from both the patients were found to be within normal limits. It was found that the activity of kynureninase in the liver of the patient was markedly reduced without addition of pyridoxal phosphate but the activity was restored to a considerable extent by the addition of an excess of pyridoxal phosphate. These findings suggest that the basic defect in the patients is an inability of apoenzyme (kynureninase) to combine normally with the coenzyme (pyridoxal phosphate). The present studies, in combination with the work of Frimpter et al. on cystathionuria, may give us biochemical understanding for so-called vitamin B6 dependency.