Hemoglobin SC Disease: Phenotypic Variability and Therapeutic Options

Abstract

Mutation in the Beta Globin Gene (HBB) leads to the formation of Hemoglobin S (HbS) and Hemoglobin C (HbC). Co-inheritance of HbS and HbC causes hemoglobin SC disease, a form of hemolytic anemia with a myriad of clinical manifestations. Valine replaces glutamic acid in the 6th position (Glu 6Val) to form HbS and Lysine replaces glutamic acid (Glu6Lys) in HbC. The interaction of HbC with HbS increases the propensity of red blood cells to sickle leading to microvascular occlusion and downstream end organ complications. Both HbS and HbC are present in approximately equal levels in HbSC red blood cells. It is interesting to note that Sickle cell trait and Hemoglobin C trait do not produce severe disease. However, the combination of HbS and HbC can produce a moderately severe disease than the sum of the effects of HbS and HbC disease. This is because the presence of HbC enhances the cellular dehydration of the red blood cell resulting in a more profound phenotype than their respective traits. Most of the evidence-based guidelines in Sickle Cell Disease (SCD) come from the Cooperative Study of Sickle Cell Disease (CSSD), which was undertaken more than 30 years ago, and there is paucity of data to this date regarding optimal management of hemoglobin SC disease [1,2].