Detection by Phenylalanine Tolerance Tests of Heterozygous Carriers of Phenylketonuria

Abstract

PAULING introduced the term ‘molecular disease’ for the hereditary condition of sickle cell anæmia, in which the clinical signs in both the heterozygous carriers with the sickling trait, and the homozygous patients with the anæmia, are explained by the fraction of abnormal hæmoglobin molecules present¹. Only a part of the total hæmoglobin is the abnormal type in the heterozygote with one abnormal gene, whereas nearly all the hæmoglobin is the abnormal type in the homozygote with two abnormal genes. An extension of this concept of molecular disease leads to the prediction that in hereditary diseases associated with the loss of activity of an enzyme, the asymptomatic heterozygotes should be identifiable by having less than the normal amount of the enzyme primarily involved in the disease².