Starch block electrophoresis of the hemoglobin has been performed for a group of adults who are the parents of children with thalassemia major. The hemoglobin electrophoretic pattern was found to be constantly abnormal in this group, in that the minor component with E-like mobility (designsated the A2 component) constituted a greater than normal proportion of the total hemoglobin. Reduced mean cell (erythrocyte) volume was likewise found to be present in all members of the patient group.
If it is assumed that typical childhood thalassemia major represents the homozygous state for the thalassemia gene, then the patient group studied constitutes a populations of adults heterozygous for thalassemia. Since microcytosis and an increase in the A2 content were constantly present in this group, they are suggested as suitable minimum diagnostic criteria for thalassemia trait.
The degree of elevation of the A2 fraction was noted to have a discontinuous distribution. Preliminary studies have demonstrated that the degree of elevation appears to be identical in affected members of single pedigrees. The discontinuity in distribution observed is thus apparently under genetic control.
The rather small difference in A2 content between some normal and some thalassemia trait adults implies that the alteration of hemoglobin synthesis is a secondary phenomenon, since such "low-valued" thalassemia traits were not different in their clinical expression. Despite the smallness of this difference, quantitation of the A2 fraction sufficed to distinguish these "low-valued" thalassemia heterozygotes from normal individuals.