Hemoglobin abnormalities- S, C, D, E, SC, SD & others

Overview

Hemoglobin is the iron-containing protein compound within red blood cells that carries oxygen throughout the body. Hemoglobin is produced by genes that control the expression of the hemoglobin protein. Defects in these genes can produce abnormal hemoglobins and anemia.

Normal hemoglobin types include:

  • Hemoglobin A (Hb A)
  • Hemoglobin A2 (Hb A2 )
  • Hemoglobin F (Hb F, fetal hemoglobin)

There are hundreds of abnormal hemoglobin variants, but only a few are common and clinically significant.

  • Hemoglobin S – causes sickle cell disease
  • Hemoglobin C – produces a mild anemia and enlarged spleen (splenomegaly)
  • Hemoglobin E – causes a mild anemia and mild enlarged spleen
  • Hemoglobin SC disease – causes a mild hemolytic anemia and moderate enlargement of the spleen
  • Hemoglobin SD disease – causes occasional sickle crises and moderate hemolytic anemia
  • Hemoglobin E/beta thalassemia – causes anemia varying in severity, from mild to severe, dependent on the beta thalassemia mutation(s) present
  • Hemoglobin S/beta thalassemia – varies in severity, depending on the beta thalassemia mutation inherited
  • Hemoglobin Constant Spring
  • Hemoglobin H
  • Hemoglobin Barts

Symptoms

Symptoms associated with hemoglobin variants can vary in type and severity depending on the variant present and whether an individual has one variant or a combination. Some are the result of an increase in the breakdown (hemolysis) of red blood cells and a shortened RBC survival, leading to anemia. Some examples include:

  • Weakness, fatigue
  • Lack of energy
  • Jaundice
  • Pale skin (pallor)

Some serious signs and symptoms include:

  • Episodes of severe pain
  • Shortness of breath
  • Enlarged spleen
  • Growth problems in children
  • Upper abdomen pain (due to stone formation in gallbladder)

Diagnosis

Laboratory testing is commonly used for diagnosis of hemoglobin abnormality. There are a couple of tests, each test provides a piece of the puzzle, giving the clinician important information about the hemoglobins that may be present. Testing typically includes:

 

Homeglobin S

Sickle cell trait

In the United States, approximately 70,000 to 100,000 Americans have sickle cell disease, most of them are African Americans:

  • About 1 in 13 African American babies is born with sickle cell trait
  • About 1 in every 365 black children is born with sickle cell disease

Sickle cell disease also affects some people who come from Hispanic, southern European, Middle Eastern, or Asian Indian backgrounds.

Individuals with sickle cell trait carry only one defective gene and typically live normal lives without health problems related to sickle cell.

If one parent has sickle cell trait and the other parent has normal hemoglobin, there is a 50 percent (1 in 2) chance with each pregnancy of having a child who has sickle cell trait.

If both parents have sickle cell trait, with each pregnancy there is a 50 percent (1 in 2) chance of having a child who has sickle cell trait, a 25 percent chance of having a child who has sickle cell disease, and a 25 percent chance of having a child with normal hemoglobin.

Sickle cell disease

People with the sickle cell disease are born with two sickle cell genes, one from each parent.

People with sickle cell disease have mostly hemoglobin S (also called sickle hemoglobin) in their red blood cells.Hemoglobin S can form hard fibers inside the red cells, causing them to reshape into sickle (banana) shape. Abnormally shaped red blood cells cannot move through blood vessels easily and at times are blocked from delivering oxygen to some body tissues.

The only cure for sickle cell disease is bone marrow or stem cell transplantation. Because these transplants are risky and can have serious side effects, they are usually only used in children with severe sickle cell disease. For the transplant to work, the bone marrow must be a close match. Usually, the best donor is a brother or sister.

There are treatments that can help relieve symptoms, lessen complications, and prolong life:

  • Antibiotics to try to prevent infections in younger children
  • Pain relievers for acute or chronic pain
  • Hydroxyurea, a medicine that has been shown to reduce or prevent several SCD complications. It increases the amount of fetal hemoglobin in the blood. This medicine is not right for everyone; talk to your health care provider about whether you should take it. This medicine is not safe during pregnancy.
  • Childhood immunizations to prevent infections
  • Blood transfusions for severe anemia. If you have had some serious complications, such as a stroke, you may have transfusions to prevent more complications.

Overall, the lives of people with any type of sickle cell disease are typically 20 to 30 years shorter than those of people who do not have it. Today, with early diagnosis and use of recently developed treatments, the life expectancy of children with sickle cell disease has increased 98 percent. For example, people with hemoglobin SS may live to age 50 or older.

Hemoglobin C

Hemoglobin C trait

About 2-3% of African Americans in the United States have hemoglobin C trait. This trait also affects people whose ancestors came from Italy, Greece, Africa, Latin America and the Caribbean region.

However, it is possible for a person of any race or nationality to have hemoglobin C trait.

People with hemoglobin C trait have red blood cells that have normal hemoglobin A and an abnormal hemoglobin – hemoglobin C. People with hemoglobin C trait have slightly more hemoglobin A than hemoglobin C.

People with hemoglobin C do not have Hemoglobin C disease or sickle cell disease. They cannot develop these diseases later in life. They can pass hemoglobin C trait to their children.

If one parent has hemoglobin C trait and the other parent has normal hemoglobin, there is a 50 percent (1 in 2) chance with each pregnancy of having a child who has hemoglobin C trait. These are the possible outcomes with each pregnancy.

  • 50 percent (1 in 2) chance of having a child with hemoglobin C trait
  • 50 percent (1 in 2) chance of having a child without hemoglobin C trait

Hemoglobin C disease

People who have inherited two copies of hemoglobin C gene have hemoglobin C disease. With hemoglobin C disease, the red blood cells contain mostly hemoglobin C. Too much hemoglobin C can reduce the number and size of red blood cells in your body, causing mild anemia. Hemoglobin C disease usually does not cause serious health problems.

If both parents have hemoglobin C trait, there is a chance of having a child with hemoglobin C disease. These are the possible outcomes with each pregnancy.

  • 25 percent (1 in 4) chance of having a child with hemoglobin C disease
  • 50 percent (1 in 2) chance of having a child with hemoglobin C trait
  • 25 percent (1 in 4) chance of having a child without trait or disease

 

Hemoglobin D

Hemoglobin D trait

People with hemoglobin D trait have red blood cells that have normal hemoglobin A and an abnormal hemoglobin-hemoglobin D. People with hemoglobin D trait have slightly more hemoglobin A than hemoglobin D.

People with hemoglobin D trait do not have hemoglobin D disease or sickle cell disease. They cannot develop these diseases later in life. They can pass hemoglobin D trait to their children.

If one parent has hemoglobin D trait and the other parent has normal hemoglobin, there is a 50 percent (1 in 2) chance with each pregnancy of having a child who has hemoglobin D trait. These are the possible outcomes with each pregnancy.

  • 50 percent (1 in 2) chance of having a child with hemoglobin D trait
  • 50 percent (1 in 2) chance of having a child without hemoglobin D trait

Hemoglobin D disease

People who have hemoglobin D disease have red blood cells that contain mostly hemoglobin D. Too much hemoglobin D can reduce the number and size of red blood cells in your body, causing mild anemia. Hemoglobin D disease is rare and usually does not cause serious health problems.

If both parents have hemoglobin D trait, there is a chance of having a child with hemoglobin D disease. These are the possible outcomes with each pregnancy.

  • 25 percent (1 in 4) chance of having a child with hemoglobin D disease
  • 50 percent (1 in 2) chance of having a child with hemoglobin D trait
  • 25 percent (1 in 4) chance of having a child without trait or disease

 

Hemoglobin E

Hemoglobin E trait

Hemoglobin E is the third most common type of hemoglobin, after hemoglobin A and hemoglobin S. Hemoglobin E is very common in people of Asian descent. It can also be found in people of African, Indian, Middle Eastern and Mediterranean descent.

People with hemoglobin E trait have both normal hemoglobin A and abnormal hemoglobin E in their red blood cells.

People with hemoglobin E trait do not have hemoglobin E disease or hemoglobin E/beta thalassemia disease. They cannot develop these diseases later in life. They can pass hemoglobin E trait on to their children.

If one parent has hemoglobin E trait and the other parent has normal hemoglobin A, there is a 50 percent (1 in 2) chance with each pregnancy of having a child with hemoglobin E trait. These are the possible outcomes with each pregnancy.

  • 50 percent (1 in 2) chance of having a child with Hemoglobin E trait
  • 50 percent (1 in 2) chance of having a child without trait

Hemoglobin E disease

People with hemoglobin E disease inherited two copies of hemoglobin E genes. People with hemoglobin E disease normally do not have serious medical problems related to the disease. People with hemoglobin E disease may have mild anemia.

If both parents have hemoglobin E trait there is a 25 percent (1 in 4) chance with each pregnancy of having a child with hemoglobin E disease. These are the possible outcomes with each pregnancy.

  • 25 percent (1 in 4) chance of having a child with Hemoglobin E disease
  • 50 percent (1 in 2) chance of having a child with Hemoglobin E trait
  • 25 percent (1 in 4) chance of having a child without trait or disease

Hemoglobin SC disease

Hemoglobin SC disease is a type of sickle cell disease. People who have Hemoglobin SC disease (also called sickle-hemoglobin C disease) have red blood cells that contain both hemoglobin S and hemoglobin C.

Under certain conditions, these red blood cells harden and take on a sickle (or banana) shape. Their shape and texture make it hard for these cells to flow through small blood vessels and deliver oxygen to different parts of the body. This can cause cell damage and pain.

Hemoglobin SC disease is more common than hemoglobin C disease, and its symptoms are similar to those of sickle cell disease but milder. However, people may have blood in the urine, an enlarged spleen, bleeding into the back of the eye (retinal hemorrhage), and damage to hip joint.

People inherit Hemoglobin SC disease from their parents. If one parent has hemoglobin C trait and the other person has sickle cell trait there is a 25 percent (1 in 4) chance with each pregnancy of having a child with sickle cell (SC) disease. Sickle cell disease is a lifelong illness that can result in serious health problems. These are the possible outcomes with each pregnancy.

  • 25 percent (1 in 4) chance of having a child with hemoglobin C trait
  • 25 percent (1 in 4) chance of having a child with sickle cell trait
  • 25 percent (1 in 4) chance of having a child with hemoglobin SC disease (sickle cell disease)
  • 25 percent (1 in 4) chance of having a child without trait or disease

 

Hemoglobin SD disease

Hemoglobin SD disease is a type of sickle cell disease. People with Hemoglobin SD disease have red blood cells that contain both sickle hemoglobin (hemoglobin S) and hemoglobin D. The type of hemoglobin D usually determines the severity of the disease. Hemoglobin S-hemoglobin D-Los Angeles (or D-Punjab) genes together creates a type of sickle cell disease with occasional sickle crises and moderate hemolytic anemia.

If one parent has hemoglobin D trait and the other person has sickle cell trait, there is a 25 percent (1 in 4) chance with each pregnancy of having a child with sickle cell (SD) disease. Sickle cell disease is a lifelong illness that can result in health problems. These are the possible outcomes with each pregnancy.

  • 25 percent (1 in 4) chance of having a child with hemoglobin D trait
  • 25 percent (1 in 4) chance of having a child with sickle cell trait
  • 25 percent (1 in 4) chance of having a child with hemoglobin SD disease (sickle cell disease)
  • 25 percent (1 in 4) chance of having a child without trait or disease

Hemoglobin S/beta thalassemia

Hemoglobin S/beta thalassemia, also called sickle beta thalassemia disease, is a type of sickle cell disease. People with sickle beta thalassemia disease inherited one hemoglobin S gene, one beta thalassemia gene.

Depending on the amount of hemoglobin produced, this type of sickle cell disease is called:

  •  Sickle beta plus (Sβ+) thalassemia
  • Sickle beta zero (Sβ0) thalassemia disease

Sickle cell – beta+ thalassemia tends to be less severe than sickle cell – beta0 thalassemia. People with sickle cell – beta0 thalassemia tend to have more irreversibly sickled cells, more frequent vaso-occlusive problems, and more severe anemia than those with sickle cell – beta+ thalassemia.

If one parent has beta thalassemia trait and the other parent has sickle cell trait, there is a 25 percent (1 in 4) chance with each pregnancy of having a child with sickle cell (Sβ) disease. Sickle cell disease is a lifelong illness that can result in serious health problems. These are the possible outcomes with each pregnancy.

  • 25 percent (1 in 4) chance of having a child with beta thalassemia trait
  • 25 percent (1 in 4) chance of having a child with sickle cell trait
  • 25 percent (1 in 4) chance of having a child with Sickle beta thalassemia disease (sickle cell disease)
  • 25 percent (1 in 4) chance of having a child without trait or disease

 

Hemoglobin E/beta thalassemia

People with hemoglobin E/beta thalassemia disease inherited one hemoglobin E gene, one beta thalassemia gene. People with hemoglobin E/beta thalassemia disease have an anemia that can vary in severity, from mild (or asymptomatic) to severe, dependent on the beta thalassemia mutation(s) present.

If one parent has hemoglobin E trait and the other parent has beta thalassemia trait there is a 25 percent (1 in 4) chance with each pregnancy of having a child with hemoglobin E/beta thalassemia (Eβ) disease. This is a lifelong illness that can result in serious health problems. People with hemoglobin E/beta thalassemia should be treated by a physician.  These are the possible outcomes with each pregnancy.

  • 25 percent (1 in 4) chance of having a child with Hemoglobin E  trait
  • 25 percent (1 in 4) chance of having a child with beta thalassemia  trait
  • 25 percent (1 in 4) chance of having a child with Hemoglobin E/beta thalassemia disease
  • 25 percent (1 in 4) chance of having a child without trait or disease

Hemoglobin Constant Spring

Hemoglobin Constant Spring is a hemoglobin variant, a normal alpha globin chain contains 141 amino acids, the variant alpha chain contains 171 amino acids, which is abnormally long. This long chain results in a low quantity of hemoglobin in the cells because the long chain protein is very unstable, and the messenger RNA for Hemoglobin Constant Spring is unstable.

 

Hemoglobin H

Hemoglobin H is an abnormal hemoglobin that occurs in some cases of alpha thalassemia. It is composed of four beta (β) globin chains and is produced due 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 H is also associated with significant breakdown of red blood cells (hemolysis) as it is unstable and tends to form solid structures within red blood cells. Serious medical problems are not common in people with hemoglobin H disease, though they often have anemia.

 

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. If a small amount of Hemoglobin Barts is detected, it usually disappears shortly after birth due to dwindling gamma chain production. These children have one or two alpha gene deletions and are silent carriers or have the alpha thalassemia trait. If a child has a large amount of Hemoglobin Barts, he or she usually has hemoglobin H disease and a three-gene deletion. Fetuses with four-gene deletions have hydrops fetalis and usually do not survive without blood transfusions and bone marrow transplants.

* The Content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition.