Sickle Cell Disease - Causes - Causes

Abnormal hemoglobin, called hemoglobin S, causes sickle cell disease.

Sickle cell disease is a genetic disorder caused by mutations in the beta globin gene that leads to faulty hemoglobin protein, called hemoglobin S. Hemoglobin S changes flexible red blood cells into rigid, sickle-shaped cells. These sickle cells can block blood flow, and result in pain and organ damage. Medical Animation Copyright © 2020 Nucleus Medical Media, All rights reserved.

Hemoglobin S gene

Sickle cell disease is an inherited disease caused by defects, called mutations, in the beta globin gene that helps make hemoglobin. Normally, hemoglobin in red blood cells takes up oxygen in the lungs and carries it through the arteries to all the cells in the tissues of the body. Red blood cells that contain normal hemoglobin are disc-shaped and flexible so that they can move easily through large and small blood vessels to deliver oxygen.

Sickle hemoglobin is not like normal hemoglobin. The mutations in the gene cause a problem when oxygen levels in the blood are lower, which occurs once the hemoglobin has delivered oxygen to the cells in the body’s tissues. With less oxygen, the abnormal hemoglobin S gene can cause rigid, nonliquid protein strands to form within the red blood cell. These rigid strands can change the shape of the cell, causing the sickled red blood cell that gives the disease its name.

Sickle-shaped cells are not flexible and can stick to vessel walls, causing a blockage that slows or stops the flow of blood. When this happens, oxygen is unable to reach nearby tissues. The lack of oxygen in tissue can cause attacks of sudden severe pain, called pain crises. These pain attacks can occur without warning, and a person who has them often needs to go to the hospital for effective treatment.

Because sickle cells cannot change shape easily, they tend to burst apart. Normal red blood cells live about 90 to 120 days, but sickle cells last only 10 to 20 days. The body is always making new red blood cells to replace the old cells. However, in sickle cell disease, the body may have trouble keeping up with how fast the cells are being destroyed. Because of this, the number of red blood cells is usually lower than normal. This condition, called anemia, can cause a person to have less energy.

Normal red cells and sickle red cells.
Normal red cells and sickle red cells. Figure A shows normal red blood cells flowing freely in a blood vessel. The inset image shows a cross-section of a normal red blood cell with normal hemoglobin. Figure B shows abnormal, sickled red blood cells blocking blood flow in a blood vessel. The inset image shows a cross-section of a sickle cell with abnormal (sickle) hemoglobin forming abnormal stiff rods.

How is the hemoglobin S gene inherited?

When the hemoglobin S gene is inherited from only one parent, and a normal hemoglobin gene—hemoglobin A—is inherited from the other, that person will have sickle cell trait. People who have sickle cell trait are generally healthy.

Only rarely do people who have sickle cell trait have complications similar to those seen in people who have sickle cell disease. But people who have sickle cell trait are carriers of a defective hemoglobin S gene, so they can pass it on when they have a child.

If the child’s other parent also has sickle cell trait or another abnormal hemoglobin gene, such as beta-thalassemia, hemoglobin C, hemoglobin D, or hemoglobin E, that child has a chance of having sickle cell disease.

Inheritance pattern for sickle cell disease
Inheritance pattern for sickle cell disease. The image shows how hemoglobin S genes are inherited. A person inherits two hemoglobin genes—one from each parent. A normal hemoglobin A gene will make normal hemoglobin. A hemoglobin S gene will make abnormal hemoglobin.

 

In the image above, each parent has one normal hemoglobin A gene and one hemoglobin S gene, which means each of their children has:

  • A 25% chance of inheriting two normal hemoglobin A genes. In this case, the child does not have sickle cell trait or disease.
  • A 50% chance of inheriting one normal hemoglobin A gene and one hemoglobin S gene. This child has sickle cell trait.
  • A 25% chance of inheriting two hemoglobin S genes. This child has sickle cell disease.

It is important to keep in mind that each time this couple has a child, the chances of that child having sickle cell disease remain the same. In other words, if the firstborn child has sickle cell disease, there is still a 25% chance that the second child will also have the disease. Both boys and girls can inherit sickle cell trait, sickle cell disease, or normal hemoglobin.

If a person wants to know whether he or she carries a sickle hemoglobin gene, a doctor can order a blood test to find out.