Sickle Cell Disease Causes and Risk Factors

Who can get sickle cell disease?

Sickle cell disease is a genetic disorder caused by mutations in hemoglobin genes, leading to a faulty hemoglobin protein, called hemoglobin S. Hemoglobin S changes flexible red blood cells into rigid, sickle-shaped cells. The sickled cells can block blood flow and cause pain and organ damage. Medical Animation Copyright © 2024 Nucleus Medical Media, All rights reserved.

People with sickle cell disease inherited two hemoglobin gene variants — one from each parent. These genes make a faulty hemoglobin protein called hemoglobin S. Sickle cell disease can also occur when a child inherits a gene for hemoglobin S (a sickle cell gene) from one parent and a gene for a different type of faulty hemoglobin, such as beta (β) thalassemia or hemoglobin C, from the other parent.

Sickle cell disease is sometimes called sickle cell anemia.

People have sickle cell trait if they inherit a copy of the sickle cell gene from one parent and a copy of the gene for normal hemoglobin, called hemoglobin A, from the other. People who have sickle cell trait make about 60% normal hemoglobin (hemoglobin A) and 40% sickle hemoglobin (hemoglobin S). They may be called carriers because they can pass on the gene for sickle hemoglobin when they have children.

How is sickle cell disease inherited?

In this image, both parents are carriers of sickle cell disease. Each parent has one gene that makes

normal hemoglobin A and one gene that makes hemoglobin S. This means each of their children has:

A 25%, or 1 in 4, chance of inheriting two copies of the gene for hemoglobin A. This child does not have sickle cell trait or disease.
A 50%, or 1 in 2, chance of inheriting one copy of the gene for hemoglobin A and one copy of the gene for hemoglobin S. This child has sickle cell trait and is a carrier of the gene for hemoglobin S.
A 25%, or 1 in 4, chance of inheriting two copies of the gene for hemoglobin S. This child has sickle cell disease. A child with sickle cell disease may also have one copy of the gene for hemoglobin S and one copy of a gene for another faulty hemoglobin.

Each time this couple has a child, the chances of the child having sickle cell disease remain the same. In other words, if the first 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 they carry a sickle cell gene, a healthcare provider can order a blood test to find out.

Do some groups have higher risk of sickle cell disease?

The disease is most common in people of African, Middle Eastern, Mediterranean, Central and South American, and South Asian origin or descent. Sickle cell disease now exists in most countries.

What should you do if you are a carrier or have the disease?

If you are planning to have children, you may want to meet with a genetic counselor. A genetic counselor can answer questions about the risk and explain the choices that are available.

What is a “sickled” cell?

Red blood cells with the normal type of hemoglobin are disc-shaped and flexible so that they can move easily through large and small blood vessels and deliver oxygen throughout the body.

Can the sickle cell gene protect against malaria?

Sickle cell disease and trait are common in parts of Africa and other areas where malaria affects many people. Studies show that having the hemoglobin S gene protects against serious malaria. The “malaria protection theory” explains why the gene mutation leading to hemoglobin S is found more often among people whose ancestry traces to areas where malaria is common. It is still important to prevent malaria in children with sickle cell disease.

Sickle hemoglobin is not like normal hemoglobin. Under low oxygen conditions, hemoglobin S transforms into stiff strands within red blood cells. These stiff strands change the shape of the cell, causing the “sickled,” or crescent-shaped, red blood cell that gives the disease its name. Sickled red blood cells are not flexible and can stick to vessel walls, which can block or slow blood flow.

This video shows red blood cells from a person with sickle cell disease transform into a variety of distorted or “sickle” shapes.

Blockage of blood flow means that the sickled cells cannot deliver oxygen to the rest of the body. This can cause attacks of sudden severe pain, called pain crises. Pain crises can occur without warning, and a person who has them often needs to go to the hospital for treatment. A pain crisis can last several hours or several days.

Sickled cells are not only stiff but also very fragile, and they tend to burst apart in a process called hemolysis . Normal red blood cells live about 90 to 120 days, but sickled 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 has trouble keeping up with the rate that the cells are being destroyed. This can lead to a low number of red blood cells, called anemia. The resulting anemia can cause a person to be easily tired with less energy.

sickle cell disease diagram — **Normal red cells and sickled 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 sickled cell with abnormal (sickle) hemoglobin S forming abnormal stiff rods.