Haemoglobin Vanderbilt (α2β289Ser→Arg): a New Haemoglobin with High Oxygen Affinity and Compensatory Erythrocytosis

Haemolysates of family members from three generations, all of whom had polycythaemia, were analysed by polyacrylamide gel electrophoresis at pH 8.8. Two closely spaced major bands were observed, one of which corresponded to Hb A and the other to a new mutant designated Hb Vanderbilt. Whole blood from a heterozygote for Hb Vanderbilt was analysed for oxygen affinity which was found to be much higher than that of normal subjects. Haemoglobin Vanderbilt was separated from Hb A using anion exchange chromatography. Cation exchange chromatography yielded a variant β chain from which a mutant peptide was identified with a structure corresponding to residues β83–89 with a Ser→Arg replacement at position 89. The oxygen affinity of 'stripped' haemolysates from the heterozygote was found to be much less sensitive to added organic phosphates than haemolysates from normal subjects. In whole blood, the decreased sensitivity to 2,3-diphosphoglycerate results in an increased oxygen affinity, thus explaining the clinical observations of tissue hypoxia and compensatory polycythaemia.