Types of Hemoglobins

There are hundreds of hemoglobin variants that involve genes both from the alpha and beta gene clusters. The list below touches on some of the more common and important hemoglobin variants.

Normal Hemoglobins :

Hemoglobin A. This is the designation for the normal hemoglobin that exists after birth. Hemoglobin A is a tetramer with two alpha chains and two beta chains (a₂b₂).
Hemoglobin A2. This is a minor component of the hemoglobin found in red cells after birth and consists of two alpha chains and two delta chains (a₂d₂). Hemoglobin A2 generally comprises less than 3% of the total red cell hemoglobin.
Hemoglobin F. Hemoglobin F is the predominant hemoglobin during fetal development. The molecule is a tetramer of two alpha chains and two gamma chains (a₂g₂).

Clinically Significant Variant Hemoglobins:

Hemoglobin S. This the predominant hemoglobin in people with sickle cell disease. The alpha chain is normal. The disease-producing mutation exists in the beta chain, giving the molecule the structure, a₂b^S₂. People who have one sickle mutant gene and one normal beta gene have sickle cell trait which is benign.
Hemoglobin C. Hemoglobin C results from a mutation in the beta globin gene and is the predominant hemoglobin found in people with hemoglobin C disease (a₂b^C₂). Hemoglobin C disease is relatively benign, producing a mild hemolytic anemia and splenomegaly. Hemoglobin C trait is benign.
Hemoglobin E. This variant results from a mutation in the hemoglobin beta chain. People with hemoglobin E disease have a mild hemolytic anemia and mild splenomegaly. Hemoglobin E trait is benign. Hemoglobin E is extremely common in S.E. Asia and in some areas equals hemoglobin A in frequency.
Hemoglobin Constant Spring. Hemoglobin Constant Spring is a variant in which a mutation in the alpha globin gene produces an alpha globin chain that is abnormally long. The result is a thalassemic phenotype. (The designation Constant Spring derives from the isolation of the hemoglobin variant in a family of ethnic Chinese background from the Constant Spring district of Jamaica.)
Hemoglobin H. Hemoglobin H is a tetramer composed of four beta globin chains. Hemoglobin H occurs only with extreme limitation of alpha chain availability. Hemoglobin H forms in people with three-gene alpha thalassemia as well as in people with the combination of two-gene deletion alpha thalassemia and hemoglobin Constant Spring.
Hemoglobin Barts. Hemoglobin Barts develops in foetuses with four-gene deletion alpha thalassemia. During normal embryonic development, the epsilon gene of the alpha globin gene locus combines with genes from the beta globin locus to form functional hemoglobin molecules. The epsilon gene turns off at about 12 weeks, and normally the alpha gene takes over. With four-gene deletion alpha thalassemia no alpha chain is produced. The gamma chains produced during foetal development combine to form gamma chain tetramers. These molecules transport oxygen poorly. Most individuals with four-gene deletion thalassemia and consequent hemoglobin Barts die in utero (hydrops fetalis). Compound Heterozygous Conditions