Classic phenylketonuria: diagnosis through heterozygote detection.

Fifty-nine male and female (pregnant and nonpregnant) normal control subjects were differentiated from 18 male and female obligate heterozygotes for classic PKU. The method of genotyping utilized midday semifasting blood P and T quantitated by ion-exchange chromatography, an empiric determinant, P-2/T, and a discriminant function (sigma), in which sigma = a(1)(P)+a(2)(T);a(1) and a(2) were computed by multivariate analysis, This method of genotyping was applied in three clinical settings. In one family hyperphenylalaninemia was differentiated from classic PKU in two sisters with elevated blood P. In a second family maternal PKU was related to microcephaly in two retarded siblings, one of whom was also homozygous for classic PKU. In a third family a diagnosis of classic PKU was established in a normal-appearing infant whose blood P concentration was elevated.