Sickle Cell Genetic Testing Basics
Sickle Cell Disease
What is sickle cell disease?
Red blood cells are normally round, like a bagel. A genetic change (called a mutation) can make red blood cells more likely to become "sickle" shaped, like a crescent moon. These abnormally shaped cells cause the symptoms and complications of sickle cell disease.
Round red blood cells are just the right size to squeeze through tiny blood vessels throughout the body called capillaries. Sickle-shaped cells get stuck in these passageways, and even in larger blood vessels, causing problems with the flow of blood. Abnormal cells also don't carry oxygen well. As oxygen in the blood goes down, more cells become abnormally shaped and the problem gets worse. Sickle-shaped cells are also fragile and tend to break apart. This leads to a lower red blood cell count, also known as anemia. That's why sickle cell disease is often called "sickle cell anemia."
Sickle-shaped red blood cells are "weeded out" by the spleen, an organ that filters and stores blood and helps to fight infections. Over time, the spleen gets "clogged up" with sickle-shaped cells and stops working. Children with sickle cell disease are more susceptible to the types of infections that the spleen normally fights, so they take an antibiotic every day for protection. But infection is only one of many complications of sickle cell disease occurring in the first two years of life. Early diagnosis of sickle cell disease can help to prevent early complications. Screening programs are the only way to identify people with sickle cell disease early enough to make a difference.
Those who suffer from sickle cell disease experience painful episodes or attacks. Episodes can be mild or severe. In more severe attacks, life-threatening problems can occur, such as a stroke or breathing problems due to fluid in the lungs. Potential complications include:
- Blood clots (thrombosis)
- Pain in various parts of the body, especially the joints
- Eye problems (proliferative retinopathy)
- Infections, such as pneumonia
- Fluid in the lungs during severe attacks
- Enlarged heart or heart murmur
- Liver problems, such as jaundice and gallstones
- Blockage of the spleen/loss of spleen function
- Kidney damage
- Painful erections (priapism)
- Bone problems (osteomyelitis and avascular necrosis)
- Leg ulcers
- Delayed growth
Sickle Cell Anemia
How common is sickle cell disease?
In the United States, sickle cell disease affects at least one in 650 African-Americans and about half as many Latin Americans. About 8 percent of African-Americans are sickle cell carriers.
In some parts of Africa, 25 percent of newborn babies carry a sickle cell disease gene. Why? Having one sickle cell gene protects against malaria. In areas where malaria is more common, there are more sickle cell carriers.
Who is at risk of sickle cell disease?
Sickle cell disease is very common among people from Africa, or who have ancestors from Africa, including African-Americans. It is most common in West Africa. Sickle cell disease also occurs in Mediterranean countries, some parts of the Middle East, central India and some Latin American countries. Although it is uncommon, a Caucasian person could have sickle cell disease.
Is there a cure?
No. Symptoms can be treated with blood transfusions and medications such as hydroxyurea. Painful episodes are less likely to occur if you avoid becoming dehydrated and over-exerted. You should also avoid extreme hot or cold temperatures. Even with excellent medical care, life expectancy is shortened for people with sickle cell disease.
A stem cell transplant can give a person with sickle cell disease the ability to make normal red blood cells. But the transplantation process is complicated and comes with many risks. This procedure is used only to treat people with very severe complications of sickle cell disease, and usually only when a fully matched sibling is available as a donor. Newer approaches to transplantation are allowing more people to get this type of treatment and this type of treatment is likely to become more widely available in the future.
The Gene For Sickle Cell Disease
What goes wrong with this gene?
Hemoglobin is the part of the red blood cell that attaches to oxygen and carries it through the bloodstream. Hemoglobin is made of a combination of proteins called globin proteins. Hemoglobin normally contains alpha- and beta-globins.
The beta-globin gene tells the body how to make beta-globin protein. A person with sickle cell disease has a change (or mutation) in the beta-globin gene. The change in the gene causes the body to make beta-globin protein incorrectly. When the altered beta-globin is used to make hemoglobin it causes the hemoglobin to change to a sickle shape, and this shape leads to the symptoms and complications of sickle cell disease.
The most common change in the beta-globin gene causes an altered hemoglobin molecule, called hemoglobin S. If you inherit two genes that produce hemoglobin S, you have hemoglobin SS disease, which is the typical form of sickle cell disease.
The other common change in the beta-globin gene causes the gene to produce hemoglobin C. This altered form of hemoglobin can also form a sickle shape. If you inherit one gene making hemoglobin S and the other one making hemoglobin C, you have hemoglobin SC disease. This is a slightly milder form of sickle cell disease, but it still causes a lot of problems. Having two hemoglobin C mutations is uncommon and causes a very mild type of anemia.
There are a few other, less common, changes in the beta-globin gene. If any one of these less common changes combines with the hemoglobin S change, it usually results in a milder form of sickle cell disease.
Should You Be Tested?
What is my risk of being a sickle cell-disease carrier?
Your chances of being a carrier depend on your family history and your family's ethnic background. If someone in your immediate family has sickle cell disease or sickle cell trait, you could be a carrier. Sickle cell trait is the common term for a sickle cell carrier. If you have a brother or sister with sickle cell disease, there's a two-thirds chance that you are a carrier. If one of your parents is a carrier, meaning they have sickle cell trait, and the other one is not, you have a 50-percent chance of being a carrier.
You also have a higher chance of being a carrier if your ancestors are from a part of the world where sickle cell disease is common. These areas include: Africa (especially West Africa), Mediterranean countries, some parts of the Middle East, central India and some Latin American countries. It is possible for someone to carry a gene for sickle cell even if their ancestors are not from one of these areas, but it is less likely.
Understanding Test Results and Options
How Do You Make Sense Of The Results?
If I test positive, what does that mean for me and my family?
If your child has sickle cell disease, you and your partner are both carriers of the altered beta-globin gene. Carriers do not have the disease; they have one normal copy of the gene and one altered copy. You only need one "working" copy to avoid having symptoms. If you're a carrier, one or both of your parents must have been a carrier too. This means your brothers and sisters have at least a 50-percent chance of having inherited the gene from one of your parents.
Could I get a positive test result, but not carry the disease gene (a "false" positive)?
Both tests — hemoglobin electrophoresis test and DNA test — are very specific. These tests only tell you there is a problem if there really is one. There are essentially no false positives.
Could I get a negative test result, but actually have the disease (a "false" negative)?
The hemoglobin electrophoresis will find anybody who has a sickle cell gene. The DNA test for sickle cell disease detects more than 99 percent of carriers. If you took either test, you would have less than a 1 percent chance of receiving a false negative.
How will I cope if the test shows I am a sickle cell carrier?
A carrier does not have sickle cell disease. Carriers seem to live normal life spans, and only get symptoms of sickle cell under very unusual conditions involving low oxygen or severe dehydration. Carriers should avoid flying in un-pressurized aircraft or getting very dehydrated. The most significant effect of being a sickle cell carrier is that your children could inherit the sickle cell gene from you.
If I have the sickle cell gene, can I have children who don't have the gene?
Yes, but you need to "do the math" to understand the risks of passing on the mutated gene.
If you're a sickle cell carrier and your partner is not, you have a 50-percent chance of passing the gene to each child. Even if your child inherits your copy of the sickle cell gene, the child will NOT have sickle cell, but simply be a carrier, like you.
If you and your partner are both sickle cell carriers, your child has a:
- 25-percent chance of inheriting sickle cell (two copies of the sickle cell gene)
- 50-percent chance of being a carrier (one sickle cell gene and one normal gene)
- 25-percent chance of not being a carrier (two normal genes)
During pregnancy, can I determine the risk my baby has for developing sickle cell disease?
To discover whether your unborn child has inherited sickle cell, you and your partner can seek prenatal testing. The first step is to be tested to find out if you and your partner are both sickle cell carriers. If one or both of you are NOT carriers, then your baby will not have sickle cell disease. If you are both carriers, then your baby might have the disease.
Early in the pregnancy, a doctor can use either chorionic villus sampling or amniocentesis to get a sample of tissue from the fetus. A lab then tests the tissue to determine if the fetus has inherited the change in the beta-globin gene. A baby that inherits only one changed beta-globin gene will be a carrier. A baby that inherits two changed beta-globin genes will have sickle cell disease.
Be sure to talk with your obstetrician or a genetic counselor about your options.
If I DON'T have the sickle cell gene, can I have children who DO have the gene?
If you're not a carrier, your children cannot inherit the gene from you. They could still get the gene from your partner if he or she is a carrier, but they would not get sickle cell disease because they would only have one altered gene.
Is there any harm in finding out if I carry the gene?
Carrying the gene has no significant health implications. You may, however, feel upset if you learn that you carry a gene that could potentially cause a disease in your future children.
How does the test work?
There are two types of tests for sickle cell. Both require a blood sample.
Hemoglobin Electrophoresis Test
The hemoglobin electrophoresis test can tell you if you have normal hemoglobin (called hemoglobin A) or one of the hemoglobin variants: S or C. It can even tell you if you have some of each, which happens in people who are sickle cell carriers. Most states use this test on all newborn babies to see if they have sickle cell disease.
This test can be done as a prenatal test on tissue from a chorionic villus sampling or amniocentesis. It can also be done on blood from the parents. The DNA test looks for a change in the beta-globin gene. The test looks at the two common changes for hemoglobin S and hemoglobin C.
What does the test cost?
The hemoglobin test costs about $75. The DNA test costs about $300. Costs vary depending upon the lab.
Does insurance pay for the test?
Most health-insurance companies pay for "diagnostic testing," which means the test is being done to confirm a diagnosis in a person who already has symptoms. However, there are many different plans, and you should check whether diagnostic genetic testing is a covered service before having the test performed.
Many insurance companies will not pay for a predictive test (a test for a person who does not have symptoms), especially if there is nothing that can be done to prevent the condition (no change in patient management). In the case of hereditary hemochromatosis, there is a change in management for a person known to have the genetic changes. If you are considering this test, call your insurance company and ask about its coverage.
How long does it take to get results?
Hemoglobin results should be available in a few days. DNA test results usually take two to three weeks, but may be available faster for prenatal testing. The lab sends results to the medical center that ordered the test. You need to return to the center to learn your results.
Can a health-insurance company raise my rates or drop me from coverage if I test positive?
In 2008, the U.S. government passed a law called GINA (Genetic Information Nondiscrimination Act). This law prohibits discrimination by health insurers and employers on the basis of genetic information. Learn more here.
Also, this may depend on whether or not you have group insurance or are self-employed. People with group insurance are usually covered by both federal and state laws, while people who are self-employed are covered only by state laws. Also, the Federal Health Insurance Portability and Accountability Act (HIPAA) of 1996 prohibits health-insurance discrimination based on any "health status-related factor" (including genetic information) by group health plans. Unfortunately, this act does not apply to the self-employed.
Some states have enacted legislation to cover the gaps. Most states prohibit health-insurance companies from using genetic information to deny coverage. Other states require specific justification for the use of genetic information in denying a claim. For information about laws in individual states, click on the following links:
Learn more about life insurance, disability insurance, and long-term care insurance laws.
Learn more about health insurance laws.