The Clinical and Biosynthetic Characterization of αβ‐Thalassaemia

Summary A Cypriot family is described in which three thalassaemia genes, α‐thalassaemia 1, α‐thalassaemia 2, and β–thalassaemia, are segregating. Two siblings are heterozygous for both α‐thalassaemia 1 and β‐thalassaemia while a third child has typical haemoglobin H disease. The α‐thalassaemia β‐thalassaemia combination, which is associated with an α/β chain production ratio of unity, produces a moderate degree of anaemia with marked hypochromia and morphological changes of the red cells together with increased rates of flux of potassium across the membranes, but the red cell survival is normal. These changes m red cell morphology and metabolism are very similar to those found in the sibling with haemoglobin H disease in whom there is gross imbalance of globin chain synthesis and shortened red cell survival. These results suggest that imbalanced globin chain production is the primary cause of shortened red cell survival in thalassaemia and that changes in membrane permeability are probably of secondary importance and may, at least in part, result from factors other than globin chain imbalance.