Hb Crete, an electrophoretically neutral, unstable, high
oxygen affinity variant, was characterized by
protein and
DNA analyses in the homozygous state in a 32-year-old woman from Crete, with
erythrocytosis and microcytosis. The proband and members of her family over 3 generations, including 5 carriers of
Hb Crete, were subject to clinical, hematological and biochemical investigations, and
DNA,
RNA and
protein studies were carried out. The proband demonstrated features associated with disturbed
hemoglobin (Hb) structure and function, including
erythrocytosis and additionally a state of functional
anemia, the latter reflected by increased erythropoetin levels and cardiac output. In addition, all the carriers surprisingly had hematological and biosynthetic findings more usually associated with
thalassemia trait. The structural change in
Hb Crete only partly explains all the pathological manifestations of this variant, and other mechanisms are discussed.