HB TAYBE (ALPHA-38 OR ALPHA-39 THR DELETED) - AN ALPHA-GLOBIN DEFECT,SILENT IN THE HETEROZYGOUS STATE AND PRODUCING SEVERE HEMOLYTIC-ANEMIA IN THE HOMOZYGOUS

Several alpha-chain hemoglobin variants have been described as respons ible, in homozygous or compound heterozygous patients, for a chronic h emolytic disease that overlaps thalassemia and Heinz bodies hemolytic anemia phenotypes. These variants are present in trace amounts togethe r with some Hb H in the lysate of the patients. In the asymptomatic he terozygous carriers, they are usually not detected by electrophoretic methods. Hb Taybe is an example of such an unstable and thalassemic al pha-hemoglobin variant. This hemoglobin was observed in a young Israel i Arab woman having suffered since birth from a severe and highly rege nerative hemolytic anemia for which she was splenectomized at age sixt een. The structural abnormality was characterized by protein chemistry as the deletion o a threonine residue at position alpha38 or 39 and a ssigned to the alpha1 gene by selective DNA sequencing. This structura l modification is localized in helix C, which is a highly conserved 3( 10) helix participating in the alpha1beta2 contact and close to the al pha1beta1 interface. The propositus and two siblings, who were also an emic, were found to be homozygous for the molecular defect, although t he abnormal Hb was not detected in the latters. Consanguinity in this family demonstrated the threshold effect in the clinical manifestation s of such alpha-gene disorders since heterozygotes were clinically and biologically normal.