Hemoglobinopathies Due to Abnormal Functional Properties of Hemoglobin Molecule Part I. Stable Abnormal Hemoglobins with High Oxygen Affinity and Erythrocytosis
The hemoglobin (Hb) tetramer exists in equilibrium between two quaternary conformations R and T and any alteration that will affect this equilibrium will have a marked effect on the function of hemoglobin. As a rule, it can be stated that any amino acid substitution that would stabilize the Hb tetramer in the oxy conformation will result in a hemoglobin variant with an increased oxygen affinity. Conversely, any amino acid substitution that would favour the deoxy configuration will produce a hemoglobin mutant with decreased oxygen affinity. Since the discovery of Hb Chesapeake in 1966, more than 130 ab normal hemoglobins with an altered oxygen affinity have been reported. Out of these 77 are stable variants and the rest being unstable hemo globins. The present review describes the molecular basis of 77 stable variants with an altered oxygen affinity and a comprehensive hematological data which should be of great interest to clinicians has been presented. In many cases, these abnormal hemoglobins manifest their presence either by familial erythrocytosis or clinical cyanosis. The molecular abnormality has been caused by substitution in α1β2 contact, carboxy terminal of globin chains or 2,3 DPG binding site. Stable abnormal hemoglobins of mutation at α1β2 and α1β1 contacts with high oxygen affinity only are dealt with in the present part of this review.