Phenylketonuria as a balanced polymorphism: the nature of the heterozygote advantage

Abstract

Mothers of children with phenylketonuria have a significantly lower miscarriage rate than a matched control population in Ireland and west Scotland. This protective effect of the gene against some factor causing foetal death would seem to constitute a heterozygote advantage which might account for the previously observed polymorphism for phenylketonuria. It is suggested that the decrease in foetal mortality is mediated by the higher concentration of phenylalanine in the heterozygous mother's blood, but that this is not a simple nutritional effect of an increased supply of an essential amino acid leading to increased protein deposition.