Hemoglobin metabolism in thalassemia: In vivo studies

Abstract

1. 1. C 14-labeling of heme and globin was measured in three patients with thalassemia major and in two normal subjects after the oral administration of 100 μc. of glycine-2-C 14. The labeling of stercobilin also was measured in one patient with thalassemia. 2. 2. In the patients with thalassemia, the apparent utilization of glycine for hemoglobin synthesis was decreased, and the appearance of radioactivity in circulating hemoglobin was relatively delayed. In contrast, radioactivity appeared extremely rapidly in the fecal stercobilin, reaching a maximum on the third day, when it was over 100 times greater than the maximum radioactivity found in heme. 3. 3. The 50 per cent red cell survival was estimated in two patients with thalassemia as thirty-six and twenty-eight days, and in two normal subjects as 118 and 128 days. 4. 4. The relative labeling of heme and globin was expressed as the heme:globin ratio, which had a mean value of 0.784 in both normal subjects, and fell after the 100th day; it is suggested that the fall may be due to preferential reutilization of C 14 for globin synthesis. The ratio was significantly lower than normal in two of the three patients with thalassemia. 5. 5. These results are compatible with the concept that there is a defect in hemoglobin synthesis as well as an abnormality of erythrocyte production in thalassemia major. The enhanced early labeling of stercobilin implies an abnormal degree of premature destruction of red cells or hemoglobin within the bone marrow, or an anabolic pathway for the production of stercobilin. The basic abnormality would seem to be in the erythroblast, a genetic biochemical lesion, it is suggested, not yet identified.