Normal haemoglobin consists of four protein chains: 2 x alpha globin and 2 x beta globin. Defects in these protein chains cause the two major types of thalassaemia that are accordingly named alpha or beta.
Alpha globin: The production of enough alpha globin protein chains requires four genes. If one or more of the four genes is missing it results in alpha thalassaemia.
Beta globin: Two genes are necessary to make sufficient beta globin protein. Defects in one or both genes cause Beta Thalassaemia. Beta Thalassaemia is an autosomal recessive disorder caused by the absence or reduction of beta-globin chain synthesis, resulting in microcytic hypochromic anaemia, an abnormal peripheral blood smear with nucleated red blood cells, and reduced amounts of haemoglobin A. For clinical purposes, Beta Thalassaemia is divided into thalassaemia major, thalassaemia intermedia, and thalassaemia minor. Thalassaemia major is characterised by ineffective erythropoiesis and extramedullary hematopoiesis and is transfusion dependent. Thalassaemia major manifests within the first year of life. Individuals with thalassaemia intermedia present with symptoms later and have milder anaemia that only rarely requires transfusion. Thalassaemia minor is asymptomatic.