Haemoglobinopathy and sickle cell disease

Sickle cell disease (SCD), first described in the early twentieth century, is an inherited haemoglobinopathy resulting from a mutation on chromosome 11. The mutation causes an amino acid substitution on the b-globin subunit of normal adult haemoglobin A, resulting in the formation of haemoglobin S. Haemoglobin S is biochemically unstable and can precipitate out of solution when in the deoxygenated state, forming the pointed, slightly curved ‘sickle cells’ (Fig. 1). The greater the proportion of haemoglobin S in the cell, the greater is the propensity to sickle. The heterozygous carrier state or sickle cell trait results in the production of both haemoglobin A and S (usually 30–40% HbS), which has a predominantly benign clinical picture as the cells only sickle under extraordinary physiological conditions. Sickle cell trait provides some protection against the consequences of Plasmodium falciparum malaria. The homozygous state (with near 100% HbS) results in SCD. This is a debilitating disease characterized by chronic haemolytic anaemia, recurrent intermittent vaso-occlusion and severe pain, and progressive organ damage and early death. Survival is rare beyond the fifth decade. The HbS gene is found primarily in Africa and south-west Asia, but in light of population migration, is becoming a worldwide phenomenon. The thalassaemias are a group of hereditary anaemias caused by defective synthesis of the alpha chain (alpha thalassaemias) or the beta chain (beta thalassaemias) of haemoglobin. Heterozygotes have mild anaemia, whereas homozygotes have severe anaemia. Unbalanced synthesis of the alpha and beta chains leads to unstable haemoglobin and early red cell death, usually in the marrow. There may be a compensatory extramedullary haematopoiesis. Haemoglobin