The Interaction of α-Thalassemia with Sickle Cell Anemia

Abstract

The coinheritance of α-thalassemia (α-thal) and sickle cell anemia provides a most interesting example of how separate globin gene mutations influence clinical manifestations of abnormal gene expression. Early reports in the literature contained conflicting opinions as to whether α-thal ameliorated the clinical consequences of sickle cell disease. With the discovery that the concentration of sickle hemoglobin (Hb S) had a profound influence on both the kinetics (1) and extent (2) of deoxy Hb S polymerization, it was predicted that the lower intraerythrocytic concentration of Hb S associated with α-thal would mitigate the clinical severity of sickle cell anemia. Moreover, the use of α-globin gene mapping for objectively diagnosing α-thal revealed that one in three Black Americans were silent carriers of α-thal (3). Thus, it followed that a great many sickle cell patients may be affected by this potentially modifying influence.