Hemoglobins with high oxygen affinity leading to erythrocytosis. New variants and new concepts.
This review brings some new insights on erythrocytosis of genetic origin related to problems of oxygen delivery by hemoglobin (Hb). A few molecular mechanisms are individualized among the about 100 Hb variants that cause compensatory erythrocytosis. The most frequently observed structural modifications are localized in the alpha1beta2 interface, or at the C-terminal. They impair formation of a stable T state. Others mutations modify directly or indirectly the surrounding of the heme and the site where oxygen binds. A special interest is brought to the dose effect considering the possibility for formation of hybrid tetramers with altered oxygen binding properties. Homozygous cases, and patients who are compound heterozygotes for a high oxygen affinity Hb and a thalassemia (thal), are discussed. Several examples are provided, specially documented for Hb Olympia [beta20(B2)Val --> Met] and Hb Saint Nazaire [beta103(G5)Phe --> Ile]. Other mechanisms leading to erythrocytosis are discussed, and finally, an algorithm is proposed for etiological diagnosis.
Wajcman
Henri
H
INSERM U654, Bases Moléculaire et Cellulaires des Malades Génétiques, Hôpital Henri Mondor, Créteil, France. Henri.Wajcman@im3.inserm.fr
Galactéros
Frederic
F
D019794:2,3-Diphosphoglycerate / Q000737:chemistry / Q000378:metabolism; D014644:Genetic Variation / Q000235:genetics*; D006418:Heme / Q000737:chemistry / Q000378:metabolism; D006455:Hemoglobins, Abnormal / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D010100:Oxygen / Q000378:metabolism*; D011086:Polycythemia / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary
D006455:Hemoglobins, Abnormal; D019794:2,3-Diphosphoglycerate; D006418:Heme; D010100:Oxygen