Several α-chain hemoglobin variants have been described as responsible, in homozygous or compound heterozygous patients, for a chronic hemolytic disease that overlaps thalassemia and Heinz bodies hemolytic anemia phenotypes. These variants are present in trace amounts together with some Hb H in the lysate of the patients. In the asymptomatic heterozygous carriers, they are usually not detected by electrophoretic methods. Hb Taybe is an example of such an unstable and thalassemic α-hemoglobin variant. This hemoglobin was observed in a young Israeli Arab woman having suffered since birth fom a severe and highly regenerative hemolytic anemia for which she was splenectomized at age sixteen. The structural abnormality was characterized by protein chemistry as the deletion of a threonine residue at position α38 or 39 and assigned to the α1 gene by selective DNA sequencing. This structural modification is localized in helix C, which is a highly conserved 310 helix participating in the α1β2 contact and close to the α1β1 interface. The propositus and two siblings, who were also anemic, were found to be homozygous for the molecular defect, although the abnormal Hb was not detected in the latter. Consanguinity in this family demonstrated the threshold effect in the clinical manifestations of such α-gene disorders since heterozygotes were clinically and biologically normal.
|Number of pages
|Comptes Rendus de l'Academie des Sciences - Serie III
|Published - 1994
- Hb Taybe
- hemolytic anemia