Genetic disorders of hemoglobin oxygen affinity
- Martin H Steinberg, MD
Martin H Steinberg, MD
- Professor of Medicine, Pediatrics, Pathology and Laboratory Medicine
- Boston University School of Medicine
- Section Editors
- Donald H Mahoney, Jr, MD
Donald H Mahoney, Jr, MD
- Section Editor — Pediatric Hematology
- Professor of Pediatrics
- Baylor College of Medicine
- Benjamin A Raby, MD, MPH
Benjamin A Raby, MD, MPH
- Section Editor — Genetics
- Associate Professor of Medicine
- Harvard Medical School
Normal adult hemoglobin is a tetramer of two pairs of globin polypeptide chains, alpha chains and beta chains. Some rare mutations in these globin chains change the affinity of the hemoglobin molecule for oxygen, thereby disturbing the normal loading of oxygen in the lungs and delivery of oxygen to the tissues. (See "Structure and function of normal hemoglobins".)
Mutations in the coding sequence of globin genes that alter hemoglobin oxygen affinity and mutations in other genes that may cause polycythemia will be discussed here . Understanding these hemoglobin mutants is useful for clinicians who must diagnose and treat patients with suspected hemoglobinopathies.
The more general evaluation of patients with erythrocytosis, which may be a consequence of increased hemoglobin oxygen affinity or of other disorders that increase the production of RBCs such as polycythemia vera or smoking, is discussed separately. (See "Diagnostic approach to the patient with polycythemia".)
The normal oxygen binding characteristics of hemoglobin are displayed by the sigmoidally-shaped hemoglobin-oxygen dissociation curve and its P50, the point on the curve where the hemoglobin molecule is half-saturated with oxygen.
●When a hemoglobin's affinity for oxygen is high (ie, lowP50), oxygen delivery to tissues is impaired, stimulating erythropoietin production and increasing the red cell mass, resulting in erythrocytosis.
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- Modifiers of oxygen affinity
- HIGH OXYGEN AFFINITY HEMOGLOBINS: ERYTHROCYTOSIS
- Alterations affecting the R—>T transition
- - Hb Chesapeake
- - Hb Montefiore
- Alteration in the alpha1beta1 area of contact
- - Hb Crete
- Mutations that decrease the affinity of hemoglobin for 2,3-BPG
- High affinity hemoglobins of uncertain mechanism
- Diagnosis of a high oxygen affinity hemoglobin
- - High oxygen affinity hemoglobins and other red cell defects
- - Activating mutations of the erythropoietin receptor
- - Idiopathic familial erythrocytosis
- Clinical manifestations and treatment
- LOW OXYGEN AFFINITY HEMOGLOBIN MUTANTS: CYANOSIS
- Alterations affecting the R—>T transition
- Hb Kansas
- Hb Beth Israel
- Hb Saint Mande
- Hb Bruxelles
- SUMMARY AND RECOMMENDATIONS