Severe inclusion body beta-thalassaemia with haemolysis in a patient double heterozygous for beta degrees-thalassaemia and quadruplicated alpha-globin gene arrangement of the anti-4.2 type

We describe a new case of an association of alpha-globin gene quadruplicati on of the anti-4.2 type with beta degrees-thalassaemia. The patient, a youn g woman of mixed Brazilian-Portuguese origin, suffered from chronic haemoly tic anaemia with splenomegaly. Bone marrow supravital staining with brillia nt cresyl blue and electron microscopy studies showed large inclusion bodie s in about 3% of erythroblasts. Upon immunofluorescent staining these inclu sions reacted with a monoclonal antibody to alpha- but not to beta-globin. Analysis of alpha-globin cluster by Southern blotting showed the presence o f pathologic fragments specific for the anti-4.2 alpha-globin gene quadrupl ication. alpha/beta mRNA ratio was higher than in cases combining alpha-glo bin triplication and beta degrees-thalassaemia or in cases of beta degrees- thalassaemia heterozygous stale alone (18, 14.7 and 10.1 respectively). Our data confirmed the hypothesis that the clinically detectable haemolysis in this beta degrees-thalassaemic patient was due to an unusually high amount of precipitated alpha-globin in erythroid precursors, This considerable ex cess of alpha-globin chains was due partly to the beta-globin deficit cause d by the presence of the beta degrees-thalassaemic gene, but also to the pr esence of 6 active alpha-globin genes resulting from alpha-globin gene quad ruplication in one chromosome.