Severe inclusion body beta-thalassaemia with haemolysis in a patient double heterozygous for beta(0)-thalassaemia and quadruplicated alpha-globin gene arrangement of the anti-4.2 type.

Abstract

We describe a new case of an association of alpha-globin gene quadruplication of the anti-4.2 type with beta(0)-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 alpha- but not to beta-globin. Analysis of alpha-globin cluster by Southern blotting showed the presence of pathologic fragments specific for the anti-4.2 alpha-globin gene quadruplication. Alpha/beta mRNA ratio was higher than in cases combining alpha-globin triplication and beta(0)-thalassaemia or in cases of beta(0)-thalassaemia heterozygous state alone (18, 14.7 and 10.1 respectively). Our data confirmed the hypothesis that the clinically detectable haemolysis in this beta(0)-thalassaemic patient was due to an unusually high amount of precipitated alpha-globin in erythroid precursors. This considerable excess of alpha-globin chains was due partly to the beta-globin deficit caused by the presence of the beta(0)-thalassaemic gene, but also to the presence of 6 active alpha-globin genes resulting from alpha-globin gene quadruplication in one chromosome.

• Authors: P Beris, M Solenthaler, S Deutsch, R Darbellay, A Tobler, M L Bochaton-Pialat, G Gabbiani
• Journal: British journal of haematology (Br J Haematol) Vol. 105 Issue 4 Pg. 1074-80 (Jun 1999) ISSN: 0007-1048 [Print] England
• PMID: 10554822 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Messenger
• Globins

Topics

• Anemia, Hemolytic (genetics)
• Blotting, Southern
• Female
• Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor
• Globins (genetics)
• Heterozygote
• Humans
• Inclusion Bodies
• Microscopy, Electron
• Mutation (genetics)
• RNA, Messenger (metabolism)
• beta-Thalassemia (genetics, pathology)