Mild thalassemia: the result of interactions of alpha and beta thalassemia genes.
Homozygous thalassemia is due to inherited unbalanced synthesis of the alpha- or beta-chains of hemoglobin. Clinical severity may be in part related to the extent of alpha:beta imbalance. Two families are presented that illustrate this concept. Thalassemia in these individuals was evaluated by clinical and genetic criteria. The relative rates of alpha- and beta-chain synthesis in their reticulocytes were estimated by the extent of incorporation of 1-leucine-U-(14)C into the chains. Unusual combinations of clinical and hematological data and biosynthetic ratios were obtained in certain individuals which indicated the presence of combinations of alpha- and beta-thalassemia genes. The propositus of the first family had mild Cooley's anemia and was believed to have one alpha- as well as two beta-thalassemia genes. Presumably the alpha-thalassemia gene interfered with alpha-chain production which lead to less accumulation of alpha-chains and a reduced rate of intramedullary and peripheral hemolysis. In the second family two individuals were believed to have an alpha-thalassemia, a "silent carrier," and a beta-thalassemia gene. Despite the fact that they appeared to have the genotype of hemoglobin H disease, their cells contained no hemoglobin H and had a normal lifespan presumably because excess beta-chain production was inhibited by the beta-thalessemia gene. These family studies suggest that the alpha:beta imbalance observed in thalassemia may be favorably influenced by combinations of alpha- and beta-thalassemia genes.
D000328:Adult; D001853:Bone Marrow; D002247:Carbon Isotopes; D002845:Chromatography; D004906:Erythrocyte Count; D005796:Genes; D005838:Genotype; D006452:Hemoglobinometry; D006454:Hemoglobins / Q000096:biosynthesis; D006461:Hemolysis; D006801:Humans; D007930:Leucine / Q000378:metabolism; D008297:Male; D010375:Pedigree; D012156:Reticulocytes / Q000032:analysis / Q000378:metabolism; D013789:Thalassemia / Q000175:diagnosis / Q000235:genetics*
D002247:Carbon Isotopes; D006454:Hemoglobins; D007930:Leucine