Thalassaemia syndromes: SAQ

Part A — Pathophysiology and diagnosis (10 marks)

Beta-thalassaemia major is an autosomal recessive disorder in which the beta-globin chain is made too slowly or not at all, while the alpha chain continues at the normal rate. The unpaired alpha chains are unstable, they precipitate inside the developing red cell precursors, and the precursors die in the marrow, a process called ineffective erythropoiesis that is the dominant cause of the severe microcytic anaemia. The red cells that reach the circulation are fragile and are destroyed in the spleen, adding chronic haemolysis. The child is well at birth because fetal haemoglobin, made of alpha and gamma chains, carries the oxygen, and the disease declares itself only as the fetal haemoglobin falls between six and twelve months. ^[12][6]

The diagnosis is made by haemoglobin separation. Before any transfusion, the electrophoresis or high-performance liquid chromatography shows a markedly raised haemoglobin F, often over 70 percent, with haemoglobin A absent in the beta-zero form or greatly reduced in the beta-plus form, and a raised haemoglobin A2. The full blood count shows a severe microcytic, hypochromic anaemia with a high red cell count, target cells, and an inappropriately low reticulocyte count for the degree of haemolysis. The diagnosis is most reliable when it is made before the first transfusion, because a transfused child carries the donor haemoglobin A. ^[12]