title: 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.affiliation: Division of Haematology, Geneva University Hospital, Switzerland. photis.beris@hcuge.ch
authors.forename: P
authors.initials: P
authors.lastname: Beris
authors.forename: M
authors.initials: M
authors.lastname: Solenthaler
authors.forename: S
authors.initials: S
authors.lastname: Deutsch
authors.forename: R
authors.initials: R
authors.lastname: Darbellay
authors.forename: A
authors.initials: A
authors.lastname: Tobler
authors.forename: M L
authors.initials: ML
authors.lastname: Bochaton-Pialat
authors.forename: G
authors.initials: G
authors.lastname: Gabbiani
mesh_terms: D000743:Anemia, Hemolytic / Q000235:genetics*; D015139:Blotting, Southern; D005260:Female; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D005914:Globins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D002479:Inclusion Bodies; D008854:Microscopy, Electron; D009154:Mutation / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D017086:beta-Thalassemia / Q000235:genetics* / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D005914:Globins