A 30-year-old West African man with chronic hemolytic anemia has an abnormal hemoglobin on HPLC. Hemoglobin electrophoresis shows a band migrating toward the anode more than HbS at alkaline pH. Oxygen affinity is markedly increased. Which mutation is most likely?

• A HbS (beta-6 Glu→Val) causing sickling under deoxygenation
• B Hemoglobin Chesapeake (alpha92 Arg→Leu) causing high-oxygen-affinity hemoglobin with erythrocytosis ✓
• C HbM (alpha or beta chain histidine→tyrosine) causing methemoglobinemia
• D Hemoglobin H disease (4 beta chains) with Heinz body formation

Explanation

High-oxygen-affinity hemoglobins arise from mutations that stabilize the R (relaxed/oxy) conformation of hemoglobin, reducing oxygen release to tissues. This causes tissue hypoxia, secondary erythrocytosis, and a left-shifted oxygen dissociation curve. Hemoglobin Chesapeake (alpha92 Arg→Leu) disrupts the alpha1-beta2 interface contact important for the T→R conformational switch. These variants typically cause erythrocytosis without hemolytic anemia and are distinct from HbS (right-shifted, hemolytic). Hemoglobin M variants cause methemoglobinemia with cyanosis. HbH is a severe thalassemia.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.