Genotype phenotype relationships in β thalassaemias

Abstract

The homozygous state for β-thalassaemia usually results in thalassaemia major, which requires monthy blood transfusions and regular infusions of the iron chelating agent desferrioxamine, for life. Some patients are less severely affected and survive either with no blood transfusion or without regular blood transfusion. This milder syndrome is termed thalassaemia intermedia. A significant amount of genetic information is now available in order to predict the thalassaemia intermedia phenotype from the genotype. Important ameliorating genetic factors are mild β-thalassaemia mutations, co-inheritance of α-thalassaemia, and presence of polymorphisms adjacent to the β-globin gene complex or mutations that increase HbF production by enhancing gamma-globin chain production. Accurate and precise prediction of phenotype from genotype will have important implications for prenatal diagnosis. Early diagnosis of thalassaemia intermedia is also important in order to avoid treatment with regular blood transfusions as for thalassaemia major, since a significant part of the morbidity and mortality arises from iron overload due to regular transfusion.