13-16: Hemoglobin C Disorders

Hemoglobin C is formed by a single amino acid substitution at the same site as in sickle hemoglobin (codon 6 of the beta globin gene) but with lysine instead of valine substituted for glutamate. Hemoglobin C is nonsickling but may participate in polymer formation in association with hemoglobin S. Homozygous hemoglobin C disease produces a mild hemolytic anemia with splenomegaly, mild jaundice, and pigment (calcium bilirubinate) gallstones. The peripheral blood smear shows generalized red cell targeting and occasional cells with angular crystals of hemoglobin C (eFigure 13–15). Persons heterozygous for hemoglobin C are clinically normal.

Patients with hemoglobin SC disease are compound heterozygotes for beta^S and beta^C. These patients, like those with sickle beta⁺-thalassemia, have a milder hemolytic anemia and milder clinical course than those with homozygous SS disease and they live longer. There are fewer vaso-occlusive events, and the spleen remains palpable in adult life. However, persons with hemoglobin SC disease have more retinopathy and more priapism than those with SS disease. The hematocrit is usually 30–38%, with 5–10% reticulocytes, and compared to SS, fewer irreversibly sickled cells on the blood smear. Target cells are more numerous than in SS disease. Hemoglobin electrophoresis will show approximately 45–50% hemoglobin C, 50% hemoglobin S, and no increase in hemoglobin F levels.