Hb Taybe (alpha 38 or 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 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 alpha-hemoglobin variant. This hemoglobin was observed in a young Israeli Arab woman having suffered since birth from 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 alpha 38 or 39 and assigned to the alpha 1 gene by selective DNA sequencing. This structural modification is localized in helix C, which is a highly conserved 3(10) helix participating in the alpha 1 beta 2 contact and close to the alpha 1 beta 1 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 latters. Consanguinity in this family demonstrated the threshold effect in the clinical manifestations of such alpha-gene disorders since heterozygotes were clinically and biologically normal.
Galacteros
F
F
INSERM U. 91, Hôpital Henri Mondor, Créteil, France.
Girodon
E
E
M'Rad
A
A
Martin
J
J
Goossens
M
M
Jaber
L
L
Cohen
I J
IJ
Tamary
H
H
Goshen
Y
Y
Zaizov
R
R
D000328:Adult; D000745:Anemia, Hemolytic, Congenital / Q000097:blood*; D005260:Female; D005914:Globins / Q000648:ultrastructure*; D006455:Hemoglobins, Abnormal / Q000235:genetics* / Q000648:ultrastructure; D006720:Homozygote; D006801:Humans; D010375:Pedigree; D016133:Polymerase Chain Reaction
D006455:Hemoglobins, Abnormal; D005914:Globins