Severe inclusion body β-thalassaemia with haemolysis in a patient double heterozygous for β°-thalassaemia and quadruplicated α-globin gene arrangement of the anti-4.2 type

Abstract

We describe a new case of an association of α-globin gene quadruplication of the anti-4.2 type with β°-thalassaemia. The patient, a young woman of mixed Brazilian-Portuguese origin, suffered from chronic haemolytic anaemia with splenomegaly. Bone marrow supravital staining with brilliant cresyl blue and electron microscopy studies showed large inclusion bodies in about 3% of erythroblasts. Upon immunofluorescent staining these inclusions reacted with a monoclonal antibody to α- but not to β-globin. Analysis of α-globin cluster by Southern blotting showed the presence of pathologic fragments specific for the anti-4.2 α-globin gene quadruplication. α/β mRNA ratio was higher than in cases combining α- globin triplication and β°-thalassaemia or in cases of β°-thalassaemia heterozygous state alone (18, 14.7 and 10.1 respectively). Our data confirmed the hypothesis that the clinically detectable haemolysis in this β°- thalassaemic patient was due to an unusually high amount of precipitated α- globin in erythroid precursors. This considerable excess of α-globin chains was due partly to the β-globin deficit caused by the presence of the β°- thalassaemic gene, but also to the presence of 6 active α-globin genes resulting from α-globin gene quadruplication in one chromosome.