Hemoglobin is a carrier for oxygen from the lungs to the various tissues and carbon dioxide from other parts of the body to the lungs. About 70% of the body’s iron is present in the red blood cells in the form of hemoglobin. Hemoglobin is an iron-protein complex that gives red blood cells its red color. It is made up of heme, which is the iron-containing portion, and globin chains, which are proteins. The globin protein consists of chains of amino acids, the “building blocks” of proteins.
There are several different types of globin chains, named alpha, beta, delta, and gamma.
Normal hemoglobin types include:
- Hemoglobin A (Hb A): makes up about 95%-98% of hemoglobin found in adults; it contains two alpha (α) chains and two beta (β) protein chains.
- Hemoglobin A2 (Hb A2 ): makes up about 2%-3% of hemoglobin found in adults; it has two alpha (α) and two delta (δ) protein chains.
- Hemoglobin F (Hb F, fetal hemoglobin): makes up to 1%-2% of hemoglobin found in adults; it has two alpha (α) and two gamma (γ) protein chains. It is the primary hemoglobin produced by the fetus during pregnancy; its production usually falls shortly after birth and reaches adult level within 1-2 years.
Genetic changes (mutations) in the globin genes cause alterations in the globin protein, resulting in structurally altered hemoglobin, such as hemoglobin S, which causes sickle cell, or a decrease in globin chain production (thalassemia). In thalassemia, the reduced production of one of the globin chains upsets the balance of alpha to beta chains and causes abnormal hemoglobin to form (alpha thalassemia) or causes an increase of minor hemoglobin components, such as Hb A2 or Hb F (beta thalassemia).
Four genes code for the alpha globin chains, and two genes (each) code for the beta, delta, and gamma globin chains. Mutations may occur in either the alpha or beta globin genes. The most common alpha-chain-related condition is alpha thalassemia. The severity of this condition depends on the number of genes affected.
Mutations in the beta gene are mostly inherited in an autosomal recessive fashion. This means that the person must have two altered gene copies, one from each parent, to have a hemoglobin variant-related disease. If one normal beta gene and one abnormal beta gene are inherited, the person is heterozygous for the abnormal hemoglobin, known as a carrier. The abnormal gene can be passed on to any children, but it generally does not cause symptoms or significant health concerns in the carrier.
If two abnormal beta genes of the same type are inherited, the person is homozygous. The person would produce the associated hemoglobin variant and may have some associated symptoms and potential for complications. The severity of the condition depends on the genetic mutation and varies from person to person. A copy of the abnormal beta gene would be passed on to any children.
If two abnormal beta genes of different types are inherited, the person is “doubly heterozygous” or “compound heterozygous”. The affected person would typically have symptoms related to one or both of the hemoglobin variants that he or she produces. One of the abnormal beta genes would be passed on to children.
Red blood cells containing abnormal hemoglobin may not carry oxygen efficiently and may be broken down by the body sooner than usual (a shortened survival), resulting in hemolytic anemia. Several hundred hemoglobin variants have been documented, but only a few are common and clinically significant. Some of the most common hemoglobin variants include hemoglobin S, the primary hemoglobin in people with sickle cell disease that causes the red blood cell to become misshapen (sickle), decreasing the cell’s survival; hemoglobin C, which can cause a minor amount of hemolytic anemia; and hemoglobin E, which may cause no symptoms or generally mild symptoms.
A hemoglobin abnormality is a variant form of hemoglobin that is often inherited and may cause a blood disorder (hemoglobinopathy).
Several hundred abnormal forms of hemoglobin (variants) have been identified, but only a few are common and clinically significant.
Common hemoglobin variants
- Hemoglobin S: this is the primary hemoglobin in people with sickle cell disease (also known as sickle cell anemia). Approximately 1 in 375 African American babies are born with sickle cell disease, and about 100,000 Americans live with the disorder, according to the Centers for Disease Control and Prevention. Those with Hb S disease have two abnormal beta chains and two normal alpha chains. The presence of hemoglobin S causes the red blood cell to deform and assume a sickle shape when exposed to decreased amounts of oxygen (such as might happen when someone exercises or has an infection in the lungs). Sickled red blood cells are rigid and can block small blood vessels, causing pain, impaired circulation, and decreased oxygen delivery, as well as shortened red cell survival. A single beta (βS) copy (known as sickle cell trait, which is present in approximately 8% of African Americans) typically does not cause significant symptoms unless it is combined with another hemoglobin mutation, such as that causing Hb C or beta-thalassemia.
- Hemoglobin C: about 2-3% of African Americans in the United States are heterozygotes for hemoglobin C (have one copy, known as hemoglobin C trait) and are often asymptomatic. Hemoglobin C disease (seen in homozygotes, those with two copies) is rare (0.02% of African Americans) and relatively mild. It usually causes a minor amount of hemolytic anemia and a mild to moderate enlargement of the spleen.
- Hemoglobin E: Hemoglobin E is one of the most common beta chain hemoglobin variants in the world. It is very prevalent in Southeast Asia, especially in Cambodia, Laos, and Thailand, and in individuals of Southeast Asian descent. People who are homozygous for Hb E (have two copies of βE) generally have mild hemolytic anemia, microcytic red blood cells, and mild enlargement of the spleen. 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 Abnormalities | Lab Tests Online https://labtestsonline.org/conditions/hemoglobin-abnormalities
Sickle cell disease – GeneticsHomeReference. https://go.usa.gov/x8VbM
Dr Pooja Chhawcharia – Hemoglobin levels and its significance. https://blog.ekincare.com/2016/07/20/hemoglobin-levels-and-its-significance