The α and β chains of haemoglobin are synthesized independently under separate genetic control and in the normal state, synthesis, of the two chain is balanced. There are two main groups of thalassaemia, one affecting the synthesis of α chains, and the other affecting the synthesis β chains; these are called α thalassaemia and β thalassaemia respectively.
In β thalassaemia, the adequate production of β chains leads to a reduction in the amount of Hb-A in the red cell and a microcytic hypochomic anaemia results. The total haemoglobin is maintained in apart by the production of γ and δ chains and thus increased Hb-F or Hb-A₂ is usually found. The lack of β chains leads to accumulation of free uncombined α chains within the developing red cells. These chains aggregate and interfere with erythroid cell maturation and function, resulting in premature destruction of the cells in the marrow and consequent ineffective erythropoiesis.
In α thalassaemia, the levels of Hb-A, Hb-F and Hb-A₂ are equally depressed since they all have α chains; there is usually a microcytic hypochromic anaemia. In the absence of sufficient α chains, excess β chains or γ chains aggregate to form Hb- (β₄) or Hb-Bart’s (γ₄). The inheritance of thalassaemia is co-dominant, and follows classic Mendelian principles. Alpha thalassaemia and Beta thalassaemia exist in both the homozygous and heterozygous states, and the genes for thalassaemia may interact with those of the haemoglobin structural variants.