Laboratory recognition of a rare hemoglobinopathy - Hemoglobins SS and SG(Philadelphia) associated with alpha-thalassemia-2

This article describes the laboratory investigation of an unusual hemoglobi nopathy involving hemoglobin (Hb) S, HbSG(Philadelphia), and alpha-thalasse mia-2 in a patient whose phenotype was HbSC by alkaline electrophoresis. Fi ndings of a mean corpuscular volume of 62 fL and microcytes on the blood sm ear were inconsistent with HbSC disease. The patient's clinical course over several years had been mildly symptomatic. Testing in our hospital laborat ory using isoelectric focusing and cation-exchange high-performance liquid chromatography to separate hemoglobins showed an unknown variant. Additiona l studies, including globin chain electrophoresis, reverse-phase high-perfo rmance liquid chromatography, and polymerase chain reaction-based DNA analy sis were performed at reference laboratories, which reported the following findings: HbG(Philadelphia) associated with alpha-thalassemia-2, HbS and Hb G(Philadelphia), and the alpha-globin deletions defining the -alpha(3.7)/-a lpha(3.7) genotype. The hemoglobin molecular defects, alpha-thalassemia-2, and the pattern of inheritance are discussed.