Failure of the alpha-thalassemia gene to decrease the severity of sickle cell anemia

Abstract

Abstract A 15-yr-old black male with homozygous sickle cell disease was severely growth retarded and had a chronic hemolytic anemia requiring transfusions. Globin chain synthetic studies of both peripheral blood reticulocytes and bone marrow cells revealed a ratio of alpha to betas globin synthesis (alpha/betas ratio) of 0.5, indicating the presence of an alpha-thalassemia gene. Messenger RNA isolated from the bone marrow of the patient was translated in the wheat germ cell-free system, and the globin synthesized had an alpha/betas ratio of 0.7. The hemolysate prepared from incubated bone marrow cells was fractionated on a Sephadex G100 column. The results showed that there was a peak of radioactivity that eluted after the hemoglobin peak. When this pooled peak was analyzed by CMC chromatography, the alpha/betas ratio was 0.9. These globin intermediates, probably dimers, may have contributed to the hemolysis in this patient.