Hemoglobin C Disorders

Key Features

• Hemoglobin C is formed by a single amino acid substitution at the same site as in sickle hemoglobin (codon 6 of the β globin gene) but with lysine instead of valine substituted for glutamine

• Hemoglobin C is nonsickling but may participate in polymer formation in association with hemoglobin S

Clinical Findings

• Homozygous hemoglobin C disease produces a mild hemolytic anemia with

  • Splenomegaly

  • Mild jaundice

  • Pigment (calcium bilirubinate) gallstones

• Compared with patients who have homozygous SS disease, those with hemoglobin SC disease have

  • Milder hemolytic anemia

  • Milder clinical course

  • Fewer vaso-occlusive events

  • More retinopathy

  • More priapism

Diagnosis

• Peripheral blood smear shows generalized red cell targeting and occasional cells with angular crystals of hemoglobin C

• Persons heterozygous for hemoglobin C are clinically normal

• Hemoglobin SC disease

  • 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 shows approximately 45–50% hemoglobin C, 50% hemoglobin S, and no increase in hemoglobin F levels

Treatment

• Folic acid 1 mg orally daily is advised; other treatment is usually necessary only for acute problems

• Splenectomy is occasionally required

• Cholecystectomy may be needed

• Laser eye surgery if retinal neovascularization occurs