Globin chain precipitation, deranged iron metabolism and dyserythropoiesis in some thalassaemia syndromes.

Electron microscope studies of the erythropoietic cells have revealed two morphologically distinct types of intracellular inclusion in homozygous beta-thalassaemia and HbH disease, presumably reflecting different appearances of precipitated alpha- and beta-chains, respectively. Inclusions resembling those seen in homozygous beta-thalassaemia are also seen in HbE/beta-thalassaemia and to a lesser extent in heterozygous beta-thalassaemia. Dyserythropoietic changes including those indicative of deranged iron metabolism, are seen in some erythropoietic cells in all of the above-mentioned thalassaemia syndromes. Several of these changes are most prominent in homozygous beta-thalassaemia and HbE/beta-thalassaemia, less marked in heterozygous beta-thalassaemia and least prominent in HbH disease. There are gross disturbances of proliferation and protein biosynthesis in erythroblasts in homozygous beta-thalassaemia but not in HbH disease and this difference is reflected in a much greater degree of ineffective erythropoiesis in the former than in the latter. Results of studies into the relationship between the extent of alpha-chain precipitation in individual cells and both the disorder of proliferation and of protein biosynthesis are consistent with the view that these functional disturbances are related to the presence of precipitated alpha-chains and/or an expanded intracellular soluble alpha-chain pool. Some alpha-chains precipitate on centrioles and, presumably, thereby interfere with mitosis. The biochemical changes in the cell membrane of thalassaemic erythroblasts which result in their recognition and phagocytosis by macrophages remain to be determined.