Thalassemia in southeast Asia: determination of different degrees of severity of anemia in thalassemia.

beta (0)-Thalassemia/Hb E in Southeast Asia varies greatly in severity, with hemoglobin levels ranging from 2.5 to 13.5 g/dl, averaging 7.7 g/dl. Results of systematic investigations to find out what determines different levels of severity are reviewed. Concomitant inheritance of alpha-thalassemia significantly decreases the severity. Different degrees of severity in the majority of cases, however, is not due to alpha-thalassemia. Concordance of hemoglobin levels among patients who are sibs prevails, suggesting polygenic factor determinants. Potential factors ruled out as determinants for different levels of severity are discriminating fetal hemoglobin production, erythrocyte superoxide dismutase activity, reticulo-endothelial function, and failure of erythropoiesis compensation. Red cell survival and globin synthesis studies indicate that different degrees of excess of alpha-chains leading to different red cell pathology and survival are responsible for variable severity. Degrees of excess of alpha-chains in this circumstance are probably mainly determined by erythrocyte proteolytic activity. The relationship between the hemoglobin levels and erythrocyte cytosol proteolytic activity in 15 beta(0) -thalassemia/Hb E disease patients in whom a deletional type of alpha-thalassemia had been ruled out by DNA mapping is striking, with a correlation coefficient of 0.78. This finding suggests that modulation of erythrocyte proteolysis is another approach for treatment of thalassemia.