Hemoglobin C, S-C, D and E disease

Normal Hemoglobins include:

Hemoglobin A. This is the designation for the normal hemoglobin that exists after birth. Hemoglobin A contains two alpha (α) protein chains and two beta (β) protein chains.

Hemoglobin A2. This is a minor component of the hemoglobin found in red cells after birth and contains two alpha (α) protein chains and two beta (β) protein chains. 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 has two alpha (α) and two gamma (γ) protein chains; the primary hemoglobin produced by the fetus during pregnancy; its production usually falls to a low level shortly after birth.

The genes for hemoglobin F and hemoglobin A are closely related, existing in the same gene cluster on chromosome 11.

Hemoglobin variants occur when genetic changes in the globin genes cause alterations in the amino acids that make up the globin protein. These changes may affect the structure of the hemoglobin, its behavior, its production rate, and/or its stability. There are four genes that code for alpha globin chains and two genes that code for the beta globin chains. There are hundreds of hemoglobin variants that involve genes both from the alpha and beta gene clusters. The common hemoglobin variants include:

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, a2bS2. 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. Hemoglobin C disease is rare and relatively benign. People who have this disease, particularly children, may have episodes of abdominal and joint pain, an enlarged spleen, and mild jaundice, but they do not have severe crises, as occur in sickle cell disease.

Hemoglobin E. Hemoglobin E is one of the most common beta chain hemoglobin variants in the world. It is very prevalent in Southeast Asia. People who are homozygous for Hb E (have two copies of βE) generally have a mild hemolytic anemia, microcytic red blood cells, and a mild splenomegaly. A single copy of the hemoglobin E gene does not cause symptoms unless it is combined with another mutation, such as the one for beta thalassemia trait.

Hemoglobin H. Hemoglobin H occurs only with extreme limitation of alpha chain availability. It is a tetramer composed of four beta globin chains and is produced in response to a severe shortage of alpha (α) chains. Although each of the beta (β) globin chains is normal, the tetramer of 4 beta chains does not function normally. It has an increased affinity for oxygen, holding onto it instead of releasing it to the tissues and cells.

Hemoglobin Barts. Hemoglobin Barts develops in fetuses with alpha thalassemia. It is formed of four gamma (γ) protein chains when there is a shortage of alpha chains, in a manner similar to the formation of Hemoglobin H. Hb Bart’s disappears shortly after birth due to dwindling gamma chain production.

A person can also inherit two subunits derived from genes in the alpha gene cluster and two subunits derived from genes in the beta gene cluster. This condition is called compound heterozygous. Several different clinically significant combinations include:

Hemoglobin S-C disease. Patients with hemoglobin SC disease inherit one beta S gene and one beta C gene. Hemoglobin C interacts with hemoglobin S to produce some of the abnormalities seen in patients with sickle cell disease. On average, patients with hemoglobin SC disease have milder symptoms than do those with sickle cell disease. This is only an average, however. Some people with hemoglobin SC disease have a condition equal in severity to that of any patient with sickle cell disease.

Hemoglobin D Disease. Hemoglobin D Disease have inherited one copy of hemoglobin S and one of hemoglobin D-Los Angeles (or D-Punjab). These patients may have occasional sickle crises and moderate hemolytic anemia

Hemoglobin E (beta-thalassemia). The combination of hemoglobin E and beta-thalassemia produces a condition more severe than is seen with either hemoglobin E trait or beta-thalassemia trait. The disorder manifests as a moderately severe thalassemia that falls into the category of thalassemia intermedia.

Thalassemia. The thalassemia are a group of disorders in which the normal hemoglobin protein is produced in lower amounts than usual. The genes are defective in the amount of hemoglobin they produce.