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

Br J Haematol. 1999 Jun;105(4):1074-80. doi: 10.1046/j.1365-2141.1999.01451.x.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*
  • beta-Thalassemia / pathology

Substances

  • RNA, Messenger
  • Globins