Clinical pathology and molecular biology of the b IVS-I,6C thalassaemia in homozygous Maltese children

Abstract

The Thalassaemia syndrome results from a heterogeneous group of microcytic, haemolytic anaemias characterised by the absence or decreased production of one of the pairs of globin chains in the haemoglobin molecule. There are two common types of thalassaemia the alpha- and beta-thalassemia resulting from defects in the alpha-globin or beta-globin respectively. The imbalanced globin biosynthesis results in the aggregation and precipitation of the excess globin chains, within the maturing erythrocyte and increased intramedullary and circulatory red cell destruction. Thus the clinical picture is one of ineffective erythropoesis and haemolytic anaemia complicated by bone marrow expansion, growth retardation, bone pathology and hepatosplenomegaly. The b-thalassaemias are further classified into b⁰-thalassaemia, in which there is complete absence of normal b-globin chain, and in b⁺-thalassaemia, in which production of b-globin is decreased. Clinically, these are further classified into thalassaemia major (Cooley's anaemia, Mediterranean anaemia) and thalassaemia intermedia, both homozygous states and thalassaemia minor which is the heterozygous state. . Though over 160 mutations responsible for b-thalassaemia have been identified so far, only a few (1-3) are responsible for the disease in any ethnic group. This fact coupled with the introduction of new molecular biology techniques, have made the identification of the mutations in individual patients relatively easy. This study describes the clinical data over 13 years of patients that are homozygous for the b⁺ IVS-I,6T>C (IVS-I,6C) mutation.