A new variant form of phenylketonuria

We report a family (parents and two sets of twin girls) in which the propositus presented as a case of phenylketonuria with a somewhat less severe degree of phenylalanine intolerance than occurs in patients with classical phenylketonuria and whose phenylalanine tolerance was further impaired by giving cotrimoxazole. The trimethoprim component of cotrimoxazole reduces the phenylalanine tolerance of normal subjects but does not augment the degree of phenylalanine intolerance in patients with classical phenylketonuria. The results of the present study of the phenylalanine tolerance and the way in which cotrimoxazole modifies it in the members of this family are compatible with the segregation of an abnormal gene which causes a previously unrecognized type of phenylketonuria when it is present in the homozygous state. The possible relationship of this to other inherited biochemical lesions of the phenylalanine hydroxylase system is briefly discussed.