Hemoglobin SC occurs as a double heterozygous condition in less than 0.5% of African-Americans but can be as high as 25% in West Africa. Although Hb SC disease may produce a less severe anemia, the chance for retinal hemorrhage and renal and bone necrosis is greater due to increased blood viscosity. Most persons with Hb SC disease have splenomegaly, but significant symptoms usually do not show up until the teenage years.
The double heterozygote for Hb SD is quite rare and produces an anemia midway in severity between sickle cell disease and sickle cell trait.
The rare double heterozygote for Hb E produces an anemia similar to Hb S beta-thalassemia.