Amyotrophic Lateral Sclerosis
What is amyotrophic lateral sclerosis (ALS)?
Amyotrophic lateral sclerosis (ALS) is more commonly known as Lou Gehrig’s disease. It was named after a famous baseball player who contracted the disease. ALS causes destruction of the nerve cells responsible for coordinating communication between the brain, spinal cord and muscles. When muscles no longer receive information from the spinal cord, they begin to shrink. People with ALS lose the ability to control their muscles. The disease does not affect a person’s mental abilities. ALS is a progressive disorder because it continues to get worse over time.
People with ALS typically experience the following symptoms:
- Muscle weakness
- Muscle twitching
- Muscle wasting
- Poor coordination or clumsiness
- Muscle cramps
- Difficulty speaking or swallowing
- Increased or decreased reflexes (caused by unhealthy nerves)
- Muscles that become more rigid
Only about 5% to 10% of ALS cases are inherited. The other 90% not caused by genetics are called sporadic. The average age for someone to first see symptoms of sporadic ALS is 56. People with ALS that is genetic (it runs in the family) often see their symptoms start 10 or more years earlier. Symptoms for both causes of the disease may appear earlier or later in life.
Although ALS does not occur in distinct stages, the symptoms are progressive, meaning they get more severe over time. Symptoms depend upon which nerve groups have been damaged or destroyed.
- Early stages — The first signs of ALS are often clumsiness or weakness of the hands and arms or weakness of the muscles that control speech and swallowing.
- Later stages — The leg muscles become weak and poorly coordinated. Other muscles, such as those that control speech and swallowing, may become impaired.
- Long term — The entire body begins to weaken and shut down. Vital muscle functions, such as breathing, become impaired. This typically leads to death.
In most cases, ALS causes death a few years after symptoms begin. With inherited ALS, the disease may progress more slowly.
How common is ALS?
Every year, between one and three people out of 100,000 are diagnosed with ALS. The disease affects men slightly more than women (about four men for every three women). In a country the size of the United States, about 3,000 to 9,000 new cases per year are reported.
Who is at risk of ALS?
In most cases of ALS, there is no way to tell if someone is at risk. About 90% of ALS cases are sporadic, meaning the affected person does not have a family history of the disease or anything else that would put him or her at increased risk. In the other 10% of ALS cases, called familial, the disease runs in the family. Researchers do not know the cause of sporadic ALS or why it has genetic and non-genetic varieties.
Is my ethnic background the key to my risk?
No. Both forms of ALS (sporadic and familial) occur among people of every ethnicity and race.
Is my family history the key to my risk?
It’s not the key, but it is one factor. Almost 90% of cases occur in people who do not have a family history of the disease. Predicting who will get the sporadic form is impossible.
If you have a family history of ALS, figuring out your risk is not easy. Different families have different genes that may make different family members more or less likely to get ALS.
- Dominant inheritance. You only need to get one copy to be affected. For example, if one of your parents had ALS caused by a dominant gene, you would have a 50% chance of inheriting the changed gene from that parent.
- Recessive inheritance. You need to get one changed gene from each parent to be affected. If you only get one changed gene, you will be a carrier. Carriers do not have the disease; they have one normal copy of the gene and one altered copy. If you’re a carrier, one or both of your parents must have been carriers. This also means your brothers and sisters have at least a 50% chance of having inherited the gene from one of your parents.
- X-linked inheritance. The X and Y chromosomes make a person male (XY) or female (XX). When a man inherits a change in a gene on the X chromosome, he most likely will be affected by that disease. In the same situation, a woman will be just a carrier because she has a “backup copy” of the gene on her other X chromosome.
Is there a cure? No. However, people with ALS may benefit from technologies — for example, motorized wheelchairs and electronic communication devices — to compensate for their disabilities.
The Gene For ALS
What goes wrong with this gene?
A handful of genes have been associated with ALS. The best-understood gene is called superoxide dismutase-1 (SOD1). This gene provides the instructions to make a protein called superoxide dismutase. The SOD1 gene is important for the survival of nerves that send electrical signals from the brain to the muscles. Some scientists believe that the lack of SOD1 leaves cells more vulnerable to “programmed cell death,” a process used throughout the body to remove cells that are not functioning properly. With this type of “self-destruct” program around, the cell needs some checkpoints to prevent programmed cell death from happening in normal cells. SOD1 could be one of those checkpoints. When you don’t have SOD1, nerve cells that should stay alive might be killed off. When the nerves die, the muscles stop working.
Researchers have described more than 100 changes throughout the SOD1 gene. One change is associated with a more rapid progression of the disease, while another change is associated with a slower progression.
Most of the changes in SOD1 cause dominant ALS, meaning you only need to inherit one copy of the change to develop the disease. Changes in SOD1 account for about 20% of inherited ALS cases. Genetic testing is only available for the SOD1 gene. A small proportion of other inherited ALS cases is caused by changes in one of three genes: FUS (~5% of cases), TARDBP (2 to 6% of cases), and ANG (less than 1% of cases). Still, for most cases of inherited ALS, no specific genetic change would be found after testing these four genes.
Should You Be Tested?
What types of tests are available?
If you have ALS, you can obtain a DNA test to determine whether the disease is caused by a change in the SOD1 gene. Even if you have ALS, your chance of having a change in the SOD1 gene depends on your family history. Remember, most cases of ALS are not related to a change in the SOD1 gene. Work with your doctor to help you decide whether genetic testing makes sense for you.
If you have no symptoms of ALS, a pre-symptomatic test may tell you how likely you are to get the disease in the future. If you have a close family member, such as a parent or a sibling, who has a change in the SOD1 gene, the DNA test can identify whether you share the same change in your SOD1 gene.
Pre-symptomatic testing is controversial because the test cannot determine when you will start having symptoms of ALS or whether you will develop the disease. If you have a change in the SOD1 gene, it does not necessarily mean you will get ALS.
With few exceptions, to qualify for testing you must either have symptoms of the disease or have a close relative (parent or sibling) who has been diagnosed with the disease. Pre-symptomatic testing of children for ALS is discouraged. According to generally accepted guidelines for genetic counseling, children under 18 should not be tested for a disease that begins in adulthood unless there is specific benefit to the child.
If you are concerned about your risk for ALS, speak with a medical professional who is knowledgeable about the disease to find out if testing is appropriate for you.
Carrier testing/Prenatal testing
If you have a family history of ALS, carry a change in one of the ALS genes mentioned above and have a baby on the way, you might be curious to find out whether your child carries the same change. But even if both you and your future child have a change in one of these genes, it does not mean that either one of you will develop ALS.
Understanding Test Results and Options
How Do You Make Sense Of The Results?
The results of DNA testing for ALS are complicated and rarely provide definitive answers. That’s why testing is designed only for people who already have symptoms of ALS. You should have your results reviewed by a medical professional familiar with the test. He or she can explain how the results apply to you.
What does a positive result mean for me?
If you have symptoms of ALS and test positive for one of the genes, you already know how challenging the disease can be. If you do not have symptoms and you learn that you have inherited a genetic change found in a relative who has ALS, you might start developing symptoms around the same age as they did, but it could be many years later. The type of mutation may tell you if the disease is more likely to progress quickly or not, but these predictions are not perfect.
What does a positive result mean for my family?
If you test positive, your brothers, sisters and each of your children have a 50% chance of having inherited the gene. Your brothers and sisters may want to be tested to find out whether they carry an ALS gene. According to generally accepted principles of medical ethics, children under 18 should not be tested for adult diseases such as ALS unless there is an immediate benefit to the child.
Could I get a positive test result, but not carry the disease gene (a “false positive”)?
Yes. Sometimes testing uncovers a change in the gene that has not been seen before. When this happens, the laboratory may not know if this change causes the disease or not. Once a new change is seen in several people with ALS, but not seen in healthy people, the laboratory can say that the change causes the disease.
Could I get a negative test result, but actually have the disease (a “false negative”)?
Yes. Because more than one gene can cause ALS, not having a change in one of the four genes mentioned earlier only tells you “there’s not a change in one of those four genes.” You may still get ALS after a negative test because 90% of ALS cases are sporadic.
How will I cope if the test shows I might develop ALS?
Learning that you are affected by a serious illness is difficult. No formal research has been done on the psychological effects of genetic testing for ALS. Research on people with Huntington’s disease, another disorder that gets progressively worse, has shown that people receiving test results tend to accept the news after a period of adjustment.
People who receive negative test results also may need to cope with new feelings. Some report that they feel guilty that they did not get the disease, especially when one of their brothers or sisters was found to carry the gene.
Ultimately, everyone will deal with the information in his or her own way. Most importantly, people who undergo testing should have support available, including friends, family and professional counselors.
If I have the ALS gene, can I have children who don’t have the gene?
Yes. If you have a change in the SOD1 gene, or one of the three other genes mentioned earlier, you have a 50% chance of passing it on to each child you have.
If I DON’T have the ALS gene, can I have children who DO have the gene?
Yes. If you and your partner do not have a change in the SOD1 gene, or one of the three genes mentioned earlier, then your child cannot inherit the change from you, but it is possible that your child could have a new genetic change that has not been in the family before. Nobody knows exactly how often this happens, but the odds are against it.
How does the test work?
The ALS test requires a blood sample. A lab obtains DNA from the blood and looks at the genes associated with ALS: SOD1, FUS, TARDBP and ANG. The test can be ordered as a “panel” that looks at all four genes, or as an “a la carte” test for any one (or more) of the four genes. If the lab notes any changes from the normal sequence, the test will be reported as “positive.”
If you decide to be tested for ALS, you should do it at a medical center that has experience with presymptomatic genetic testing.
If you’re thinking about being tested, you probably have a family member with ALS. The neurologist caring for your family member can refer you to a testing center. A center has neurologists, geneticists and counselors with experience in dealing with the complicated issues related to genetic testing. You will have to sign a consent form indicating that you understand and agree to the test.
What do the tests cost?
The test costs about $500 to $900 for a single gene (depending on which gene), or about $1,500 to get all four genes at once. Costs vary slightly depending upon which lab does the testing.
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). If you are considering this test, call your insurance company and ask about its coverage.
How long does it take to get results?
The results of DNA testing for inherited ALS take about six to eight weeks. The results will not be reported directly to you. Instead, the laboratory provides the results to the medical center that ordered the test. You need to return to the center for another appointment to discuss the results. This way, your family and friends can be there for support when you receive the 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 you have group insurance or are self-employed. Both federal and state laws usually cover people with group insurance, while state laws only cover people who are self-employed. 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. Texas bans the use of genetic information by any group health plans, and Alabama prohibits discrimination based upon predisposition to cancer.
Life insurance, long-term care and disability insurance are generally not covered by these laws. People with life and disability coverage provided by their employers are unlikely to have this insurance affected by a genetic test result.