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Genetic disorders of hemoglobin oxygen affinity

Martin H Steinberg, MD
Section Editors
Donald H Mahoney, Jr, MD
Benjamin A Raby, MD, MPH
Deputy Editor
Jennifer S Tirnauer, MD


Normal adult hemoglobin (HbA) 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 erythrocytosis (polycythemia) will be discussed here [1]. 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 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, low P50), oxygen delivery to tissues is impaired, stimulating erythropoietin production and increasing the red cell mass, resulting in erythrocytosis.

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Literature review current through: Nov 2017. | This topic last updated: Oct 18, 2017.
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