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Alpha-1 antitrypsin (AAT) deficiency, often called Alpha-1 or AAT deficiency, is an inherited condition that causes a range of chronic lung and liver problems. People with Alpha-1 usually develop symptoms as adults, in their thirties and forties. The severity of Alpha-1 depends on many factors, including genes, the environment, and lifestyle choices.
Alpha-1 is caused by certain changes, or "variants" in a gene called PI (short for "protease inhibitor). A person must inherit two Alpha-1 variants, one from each parent, to develop Alpha-1. If a person inherits only one mutation, he or she is known as a "carrier." Carriers are usually healthy individuals, but they may have Alpha-1–related health risks that are important to recognize.
You were tested for the two most common gene changes known to cause Alpha-1: the S and Z variants.
These variants are involved in over 95 percent of all Alpha-1 cases that have had genetic testing.Your test showed that you have two copies of the Z variant (also called homozygous). The test also showed that you do not carry the S variant.
To date, there have been over 100 variants identified in the PI gene, but having two copies of the Z variant is the most common genetic cause of Alpha-1. People who have two copies of the Z variant (or mutation) are considered to have severe Alpha-1 deficiency because the body does not make enough AAT protein. People who have two copies of the Z variant have a significantly increased risk for developing complications related to Alpha-1 (see Chapter 2, Signs and Symptoms of Alpha-1)
Although all adults with ZZ will show signs of lung and liver abnormalities on specific screening tests, not all people with the ZZ variants develop complications. About 60 percent of people with your test results develop airflow limitation or lung disease, and about 30 to 40 percent of people over the age of 50 have some degree of liver disease. Even when people do develop complications, symptoms can range from mild to severe.
One reason is that there are lifestyle and environmental factors that contribute to Alpha-1 complications. Smoking is a major risk factor involved in developing lung disease for people who have ZZ. Studies have also shown that certain workplace and environmental exposures are significant risk factors for people who have ZZ (see Chapter 2, Environmental Risk Factors). Experts agree that people with ZZ should try to minimize their exposure to these risks.
Overall, it is estimated that Alpha-1 affects at least 100,000 people in the United States and over 1 million people worldwide. About 1 in 3000 babies born in the United States are affected with Alpha-1.
Experts agree that people with your test results, the ZZ variants, are frequently underrecognized or misdiagnosed. It is important that you share your test results with your health care team so that you can receive the most appropriate care for you. At the end of this chapter are your Lab Report and a DNA Direct Physician Letter for you to take to your doctor.
Since you have not experienced signs and symptoms related to Alpha-1, you can take action now to learn about Alpha-1 and take steps to decrease your risk of developing complications. For example, smoking is the single greatest risk factor for developing lung disease in people with a genetic risk (see Chapter 2, Risk Factors for Alpha-1).
Your doctor may recommend regular screening to identify Alpha-1-related signs and symptoms as early as possible. The earlier you are able to detect Alpha-1, the sooner you can begin appropriate treatment (see Chapter 2, Signs and Symptoms of Alpha-1).
There are other, less common complications related to Alpha-1, including skin, immune, kidney, and vascular problems. Although these conditions are rare, you should be aware that they can occur in people with Alpha-1. If you think you are experiencing any of these problems, speak with you doctor immediately to determine what evaluations and/or treatments would be most appropriate for you (see Chapter 2, Other Features of Alpha-1).
You also informed us that there is a known Alpha-1 variant (S or Z) in your family. Your test results show that you have inherited the same Alpha-1 variant. Below is a Family Letter to print and share with your relatives if you wish. Chapter 4 of this report, Family Issues, also talks about ways to share this information with relatives and what reactions you might expect.
Alpha-1 is a hereditary condition, so these test results have implications not only for your health, but that of your family, too. Since you have two copies of the Z variant, your relatives are also at risk for having these same genetic changes.
In order to develop Alpha-1, a person needs to inherit two genetic variants – one from each parent. This is called an autosomal recessive condition. Such conditions affect males and females equally.
We have two copies of each gene, including the Alpha-1 gene. When we have children, we pass on either one or the other copy of each gene. People who have two copies of the Z variant will pass on one or the other copy of the Z variant to each child. That means that all your children will carry the Z gene.
Whether or not a child is at risk for developing Alpha-1 also depends on whether or not the other parent is an Alpha-1 carrier or has Alpha-1. You can learn more about how Alpha-1 is inherited and risks for family members in Chapter 4, How Is Alpha-1 Inherited?
It is important to share your test results with relatives. This knowledge can be especially helpful to relatives who are considering pregnancy, parents who may be worried about whether they have passed on an Alpha-1 variant to their children, or those with chronic health conditions seeking a diagnosis. Remember, since you have two copies of the Z variant, this is important information for both your mother and father’s side of the family.
It is important to share your genetic test results with your doctor and to have regular check-ups. Making your doctor aware of your hereditary risk for Alpha-1 can enable you to work together to understand what screening tests, treatments, and lifestyle modifications may be appropriate for you.
Your doctor may recommend specific screening tests to determine if there is any evidence of lung or liver damage (such as lung or liver function tests) or, if complications develop, to detect complications as early as possible.
Other precautions to take include:
The single most important step you can take is to stop smoking or minimize your exposure to second-hand smoke. In people who already have lung disease, smoking can cause the condition to worsen and progress faster. Although less common, even Alpha-1 carriers can be compromised by the harmful effects of smoking. If you smoke, it is important to talk to your doctor about recommended smoking cessation strategies. Quitting smoking may not be easy, but it can mean the difference between developing lung disease or not.
Rememer, not everyone with a hereditary risk for Alpha-1 will develop complications. However, if you have, or suspect that you have, any signs and symptoms related to Alpha-1 it is important to speak with your doctor immediately. Not all treatments are right for everyone, and researchers continue to develop new treatments.
Only your doctor can decide what options are appropriate for you. You can learn more about these treatment options in Chapter 3, Next Steps.
Finally, some people who learn that they have Alpha-1, or even some people who learn that they have a genetic risk for Alpha-1, want to speak with others who have coped with Alpha-1. Further, many people wish to participate in research studies or experimental therapies. You can learn more about support resources and current clinical trials in Chapter 5, Resources.
To understand what your test results really mean, you need to consider them in context. Take time to read through this report — it can help you see the big picture and provide you with the basics for making informed decisions. Use the tabs at the top of this page to view each chapter of your report or return to the Index.
If you have further questions about your results or the information in this report, you can contact DNA Direct’s genetic experts, who are board-certified genetic counselors. Contact us toll-free at 1-877-646-0222 or email to set up a phone appointment.
We encourage you to talk with your doctor about your test result and what it means for you. Attached to this report is a letter to your doctor with detailed information about your test results and clinical resources. We suggest you take this letter and a copy of your lab report to your next doctor’s appointment. To download your Physician Letter, click the link below. To have it faxed to you, please call us at 1-877-646-0222.
Your lab report is a short, technical document that explains the scientific results of your DNA test. If you would like to see your lab report or share it with your physician, you can download it by clicking the link below. If you prefer to have it faxed to you, please call us at 1-877-646-0222.
Because genes are a family affair, we encourage you to talk with your family about your test results. Chapter 4, Family Issues includes information on how to send a family letter.
In this chapter, you will learn:
What Is Alpha-1 Antitrypsin Deficiency?
What Causes Alpha-1?
What Did My Genetic Test Look For?
Why Does Ethnicity Matter?
What Is Residual Risk?
If You Have a Family History
If You Do Not Have a Family History
Signs and Symptoms of Alpha-1
Why Do Some People Have More Serious Complications?
Prognosis for People with Alpha-1
Alpha-1 antitrypsin deficiency, often called Alpha-1 for short, is a condition that predisposes people to lung and liver disease. Alpha-1 can affect people very differently. Some people have mild or no symptoms, while others have severe complications. This is, in part, because a number of factors affect the development of Alpha-1–related disease, including genes, lifestyle behaviors, environmental exposures, and other influences that remain unknown.
Studies estimate that between 1 in 10 to 1 in 33 people in this country carry an Alpha-1 genetic variation. This means that about 25 million people in the United States and 160 million people worldwide are believed to be Alpha-1 carriers. The vast majority of people who are unaffected carriers are not aware of their carrier status.
It is estimated that Alpha-1 affects at least 100,000 people in the United States, and about 1 in 3000 babies born in the United States are affected with Alpha-1. Only about 10 percent of affected people know they have Alpha-1.
Although the gene responsible for Alpha-1 was identified over 20 years ago and more physicians have offered testing to people with classic signs and symptoms in recent years, genetic testing for Alpha-1 has not been integrated as part of routine practice. As a result of genetic testing, experts are finding that many people previously diagnosed with other related conditions are testing positive for Alpha-1...
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Now that you know your test results, what’s next? Click on the links below to learn more about what your test results mean based on your reason for testing.
If You Tested to Determine Your Carrier Status
If You Tested to Diagnose Signs and Symptoms
If You Are Considering Insurance Reimbursement
Consider what this means for your family plans:
The full content for this
chapter is available in the personalized
Alpha-1 Antitrypsin Deficiency
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In this chapter, you will learn about:
How Alpha-1 Is Inherited
Risks for Your Children
Risks for Other Members of Your Family
Talking With Your Family
Writing a Family Letter
Finding Allies
Preparing for Individual Reactions
How Families Spread Genetic Information
Coping With Emotional Reactions
Educational and Support Resources
The genetic changes that cause Alpha-1 are inherited, or passed down from generation to generation. Here’s how it works:
Our genetic code, or DNA, is the set of instructions that tells our bodies how to develop and function. DNA is like a string of beads in which each bead is a letter of the code. Genes are stretches of DNA that contain the instructions for a specific protein or cellular function. If there is a mistake or a change in one of the beads or "letters," the instructions can change. When this change causes a disease, it is called a mutation.
DNA is stored in each of our cells as chromosomes. We have 23 pairs of chromosomes. One chromosome from each pair is inherited from our mother's egg and the other from our father's sperm. Since we have two copies of each chromosome, we have two copies of each gene.
Below is a picture of a set of chromosomes, organized by each pair. The twenty-third pair determines our gender XX for women and XY for men. The PI gene, which is the gene involved in Alpha-1, is located on chromosome 14.
When we have children, we pass on only one gene from each pair of genes. If there is a mutation on one of these genes, there is a 50-50 chance (1 in 2, or 50 percent) that the mutation will be passed on to each child. If there are two mutations, one on each gene, then there is a 100 percent chance that a mutation will be passed on.
The figure below illustrates how we inherit our genes.
The full content for this
chapter is available in the personalized
Alpha-1 Antitrypsin Deficiency
report from DNA Direct.
DNA Direct has collected some of the best resources – web sites, books, and online audio and videos – to help you learn more about topics covered in your report.
Our favorite sites are marked with asterisks.
Alpha-1 Antitrypsin Deficiency (AAT)
Information on associations, patient support groups, and more.General Information About Genetics
Basic educational, scientific, and legal resources to learn more about genetics.Your Family and Genetic Risks
Tips on how to collect a family medical history and more.Finding Medical Specialists
Resources for finding medical specialists.Stopping Smoking
Support and strategies to help you stop smokingStopping Drinking
Support and strategies to help you stop drinking.Scientific Literature References
Medical journal articles and other references used to develop this report.
Here are resources that offer information and support to individuals and families with Alpha-1 antitrypsin deficiency. They include government web sites, nonprofit organizations, and clinical centers.
Government Web Sites
Genetics Home Reference
The U.S. National Library of Medicine has basic, introductory information about Alpha-1 antityrpsin on its Genetics Home Reference web site. While most of this information has been covered in this report, this is a helpful site for educating family members about the basics.
http://ghr.nlm.nih.gov/condition=alpha1antitrypsindeficiency
MedlinePlus
MedlinePlus has a comprehensive listing of links to information on Alpha-1 antitrypsin, symptoms, diagnosis, treatment, screening, nutrition, disease management, news, clinical trials, and much more. MedlinePlus is a service of the U.S. National Library of Medicine and the National Institutes of Health.
http://www.nlm.nih.gov/medlineplus/alpha1antitrypsindeficiency.html
The full content for this
chapter is available in the personalized
Alpha-1 Antitrypsin Deficiency
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