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

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.