Sickle Cell Syndromes. I. Hemoglobin SC-α-Thalassemia

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Abstract
Extract: Hematologic and globin synthesis studies were performed in a black American family in which the genes for α-thalassemia and hemoglobins (Hb) S and C were segregating. The following distribution of these abnormalities was found: father, sickle cell trait + α-thalassemia; mother, HbC trait + α-thalassemia, propositus, HbSC + α-thalassemia; older sibling, α-thalassemia trait; and younger sibling, hemoglobin H disease. The child with HbSC-α-thalassemia demonstrated more severe anemia and a more hemolytic picture than is typical of HbSC disease. Her erythrocytes exhibited decreased osmotic fragility in comparison with HbSC erythrocytes, but had an indistinguishable oxygen equilibrium curve and 2,3-diphosphoglycerate (2,3-DPG) level. Erythrocyte sickling in the patient, however, was significantly reduced, with less than 35% sickle forms observed at nearly complete oxygen desaturation. The sibling with hemoglobin H disease exhibited 26% Bart's (γ4) hemoglobin at birth, a level comparable with that seen in infants with HbH disease in Far Eastern populations. At age 5 months typical findings of mild hemoglobin H disease appeared, with HbH making up 6.5% of the total hemoglobin. Speculation: The presence of α-thalassemia in the proband of this study appeared to modify her HbSC disease so as to reduce its clinical severity as well as its pathologic potential. The ameliorative effect of α-thalassemia would appear to be related to a reduction in the intracellular hemoglobin concentration in the patient's erythrocytes, but other factors may also be responsible for these changes. Eurther study of genetically modified sickle hemoglobinopathy syndromes may ultimately aid in the development of effective means for the treatment of these disorders.