Birth weight and pathogenesis in phenylketonuria.

The birthweights of an ethnically homogeneous sample of infants with phenylketonuria, their unaffected siblings, and control infants were compared after adjusting for the effects of: mother's age, mother's date of birth, mother's height and obstetric history, the length of gestation, the infant's sex, the place and date of birth. There were no significant differences between the infants with phenylketonuria and their unaffected siblings either in adjusted or unadjusted birthweights. Control infants had slightly, but statistically significant, greater adjusted and unadjusted birthweights than the combined phenylketonuria and unaffected sibling groups. This effect of the phenylketonuria gene is a previously unreported finding but unlikely to be related to the pathogenesis of phenylketonuria. Our results do not provide support for the "justification" hypothesis that the mental and neurological defects in phenylketonuria result from prenatal tyrosine deprivation which would be reflected in lower birthweights.

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

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.