The interaction of alpha-thalassemia with sickle cell anemia

The coinheritance of alpha-thalassemia (alpha-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 alpha-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 and extent of deoxy Hb S polymerization, it was predicted that the lower intraerythrocytic concentration of Hb S associated with alpha-thal would mitigate the clinical severity of sickle cell anemia. Moreover, the use of alpha-globin gene mapping for objectively diagnosing alpha-thal revealed that one in three Black Americans were silent carriers of alpha-thal. Thus, it followed that a great many sickle cell patients may be affected by this potentially modifying influence.