Hematologic and biosynthetic studies in homozygous hemoglobin constant spring

Abstract

The elongated α-globin chains of hemoglobin Constant Spring (α(CS) chain of HbCS) are produced in low amounts such that the α(CS)-gene acts as a form of α-thalassemia; yet in the homozygous state the pathophysiological effects of this mutant are more severe than in the corresponding conditions that result from α-globin gene deletions. In studies designed to examine this discrepancy, we have demonstrated that a significant proportion of red cells produced in an HbCS homozygote has a much reduced red cell life span. Contrary to previous reports, we have been able to demonstrate the expected deficit in α-chain production in this condition and have shown that both the cessation of globin chain synthesis in vitro and the destruction of the excess β-chains occur unusually rapidly. Comparison with various deletion forms of α-thalassemia suggests that, in terms of intracellular globin chain precipitates and free β-chain pool, homozygous HbCS red cells more closely resemble those of HbH disease, with three of the four α-genes inactivated, than they do the more comparable α-thalassemia carriers with only two genes deleted.