Hematologic and biosynthetic studies in homozygous hemoglobin Constant Spring.
The elongated alpha-globin chains of hemoglobin Constant Spring (alpha cs chain of HbCS ) are produced in low amounts such that the alpha cs-gene acts as a form of alpha-thalassemia; yet in the homozygous state the pathophysiological effects of this mutant are more severe than in the corresponding conditions that result from alpha-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 alpha-chain production in this condition and have shown that both the cessation of globin chain synthesis in vitro and the destruction of the excess beta-chains occur unusually rapidly. Comparison with various deletion forms of alpha-thalassemia suggests that, in terms of intracellular globin chain precipitates and free beta-chain pool, homozygous HbCS red cells more closely resemble those of HbH disease, with three of the four alpha-genes inactivated, than they do the more comparable alpha-thalassemia carriers with only two genes deleted.
D000328:Adult; D001853:Bone Marrow / Q000648:ultrastructure; D002470:Cell Survival; D004905:Erythrocyte Aging; D004912:Erythrocytes / Q000502:physiology*; D005914:Globins / Q000235:genetics; D006454:Hemoglobins / Q000032:analysis; D006455:Hemoglobins, Abnormal / Q000378:metabolism*; D006720:Homozygote; D006801:Humans; D007700:Kinetics; D008297:Male; D008854:Microscopy, Electron; D013789:Thalassemia / Q000097:blood
D006454:Hemoglobins; D006455:Hemoglobins, Abnormal; D005914:Globins; C035541:Hemoglobin Constant Spring