Alpha-1-antitrypsin deficiency

Individual outcomes vary significantly for people with alpha-1 antitrypsin deficiency (AATD). A person’s signs and symptoms are a better predictor of prognosis than their AATD diagnosis alone. Some people with AATD live a normal lifespan with no symptoms of the disease. Many live a normal lifespan, with symptoms of the disease, if symptoms are detected early and treated properly. Avoiding smoking increases the chances for a good outcome. People who have severe lung disease or severe liver disease may face life-threatening complications, and may die due to end stage organ disease without an organ transplant. Ages of onset of lung disease are most commonly 30-40s in smokers and 50s or later in nonsmokers. Liver disease can occur in people of any age, but is more common in infants and adults over age 40. Talk to your doctor about your personal health and outlook.

According to the 2003 American Thoracic Society (ATS)/European Respiratory Society (ERS) medical guidelines, genetic testing is recommended for: Full siblings of individuals with alpha-1 antitrypsin deficiency (AATD); any adult with chronic obstructive pulmonary disease (COPD), emphysema, or incompletely reversible asthma; adults without symptoms but with persistent obstruction and risk factors; Adults with necrotizing panniculitis; Anyone with unexplained liver disease.

According to the 2003 ATS/ERS Guidelines, genetic testing should be considered for: Parent, child or more distant relative of someone with one or more abnormal SERPINA1 genes; Partner of an affected or carrier with AATD; People with a family history of COPD or liver disease not known to be AATD-related; Adolescents with persistent airflow obstruction; Symptomatic adults in countries with lower AATD incidence.

Full siblings of someone with severe alpha-1 antitrypsin deficiency (AATD) can also have severe AATD and should be tested. Parents and children of someone with severe AATD are usually carriers. Genetic testing can be done to confirm someone’s carrier status and rule out the usually low risk of having two mutations in the SERPINA1 gene (severe AATD). Any relative with chronic obstructive pulmonary disease (COPD), incompletely reversible asthma or unexplained liver disease should also be tested. The risk for more distant relatives to have AATD depends on the gene mutations in the family and the closeness of relationship.

If you want to learn whether genetic testing for AATD may be right for you or your family member, speak to your healthcare provider about a referral to see a genetic counselor near you. In the U.S., the Alpha-1 Foundation provides free telephone-based genetic counseling and you can reach this service by calling 1-800-785-3177. Genetic counselors can be found on the National Society of Genetic Counselors website.

As of 2019, more than 80 specialists in the U.S. are listed as Clinical Resource Centers (CRC) for alpha-1 antitrypsin deficiency (AATD) with the Alpha-1 Foundation. You can find the CRC closest to you at www.alpha1.org. In the U.S., you can also call the Alpha-1 Foundation genetic counselor at 800-785-3177 if you have questions about alpha-1 or access to care.

Many people with AATD receive regular care with a lung specialist called a pulmonologist. If you have the ZZ genetic type of AATD, remember to discuss liver screening with your doctor. If you have symptoms of liver disease, or diagnosed liver disease, you may see a liver specialist at a medical center near you, or locate the closest CRC liver specialist on the Alpha-1 Foundation website at https://www.alpha1.org/Healthcare-Providers/Testing-and-Treatment/Finding-an-Alpha-1-Specialist.

The Alpha-1 Foundation is committed to finding a cure for alpha-1 antitrypsin deficiency (AATD) and to improving the lives of people affected by the condition worldwide. The Alpha-1 Foundation provides numerous services and support organizations for people affected by alpha-1 and maintains a network of alpha-1 specialty centers. Visit www.alpha1.org.

AlphaNet is devoted to improving the lives of individuals with Alpha-1 through comprehensive disease management services, clinical research administration and consultative services. Visit www.alphanet.org. AlphaNet’s Big Fat Reference Guide (BFRG) is a comprehensive guide and self-management program available on the Internet for individuals living with Alpha-1. Visit www.alphanetbfrg.org.

The COPD Foundation provides patients and families with information on COPD, treatment resources, support programs and an advocacy center. Visit www.copdfoundation.org.

Speak to your healthcare provider about a referral to see a genetic counselor near you. In the U.S., the Alpha-1 Foundation provides free telephone-based genetic counseling and you can reach this service by calling 1-800-785-3177. This service is available to anyone who wants more information about alpha-1 antitrypsin deficiency, including those considering genetic testing, people who have received results, family members and healthcare providers. More information can be found at . Genetic counselors can be found on the National Society of Genetic Counselors website.

Signs of liver disease will be looked for patients with alpha-1 antitrypsin deficiency:

Many people with alpha-1 antitrypsin deficiency (AATD) receive regular care with a lung specialist called a pulmonologist. If you have the ZZ genetic type of AATD, remember to discuss liver screening with your doctor. If you have symptoms of liver disease, or diagnosed liver disease, you may see a liver specialist at a medical center near you, or locate the closest CRC liver specialist on the Alpha-1 Foundation website at https://www.alpha1.org/Healthcare-Providers/Testing-and-Treatment/Finding-an-Alpha-1-Specialist.

Your doctor should be aware that alpha-1 antitrypsin deficiency (AATD) can cause lung disease and liver disease. Your personalized screening and treatment recommendations will depend on your exact AATD genetic diagnosis and symptoms. Your doctor may reference the 2016 Guidelines for the treatment and management of alpha-1 at[link url=" http://journal.copdfoundation.org/jcopdf/id/1115/The-Diagnosis-and-Management-of-Alpha-1-Antitrypsin-Deficiency-in-the-Adult” target=”_blank”> http://journal.copdfoundation.org/jcopdf/id/1115/The-Diagnosis-and-Management-of-Alpha-1-Antitrypsin-Deficiency-in-the-Adult and may reference the Alpha-1 Foundation’s guide for healthcare providers at https://www.alpha1.org/Portals/0/Documents/HealthcareProvidersBrochure.pdf .

Alpha-1 antitrypsin deficiency (AATD) carriers have one SERPINA1gene with a mutation and one copy without it. If two AATD carriers have children together, they have a 25% (1 in 4) chance to have a child with AATD in each pregnancy. People with AATD have two SERPINA1 mutations — one in each copy of their gene. This is also called autosomal recessive inheritance, which happens equally in males and females. Any child of an AATD carrier also has a 50% chance to be a carrier, too, just like their parents. Full siblings of someone with AATD are also at risk to have the condition and should be tested.

There are different versions, or alleles, of the SERPINA1 gene (also called "PI" types). The most common allele is the "M" allele, and having two of these leads to the usual amount of alpha-1 antitrypsin in the blood and no symptoms of AATD. The "S" allele leads to medium-low levels of alpha-1 antitrypsin protein. The "Z" allele leads to very low levels of alpha-1 antitrypsin protein. Having two copies of the Z allele leads to more symptoms of AATD.

AATD carriers are those who have a mutation in one copy of their SERPINA1 gene (usually PI type "MZ" but can be "MS" or "M-Other"). Most carriers do not develop symptoms of AATD. However, recent research has shown that AATD carriers who smoke are at high risk to develop lung disease. Some AATD carriers may also have a small increased risk for liver disease. Carriers should avoid smoking and live a healthier lifestyle.

Chronic obstructive pulmonary disease (COPD) is a combination of medical problems that block the normal flow of air and oxygen: emphysema, chronic bronchitis, asthma that is not reversible, and some forms of bronchiectasis (when the airways become damaged). All of these can be complications of alpha-1 antitrypsin deficiency (AATD).

Emphysema damages the airways and air sacs in the lungs, making it difficult for the body to effectively exchange oxygen and carbon dioxide, which happens during normal breathing. Emphysema that happens as part of AATD usually damages the lower regions of the lungs, whereas emphysema caused by smoking more often affects the upper portions of the lungs.

Chronic bronchitis is characterized by swollen and inflamed airways that produce more mucus than usual in someone. The inflammation and mucus narrow the airways, making it difficult for air and oxygen to flow freely to the body. This often results in a chronic cough.

Alpha-1 antitrypsin deficiency (AATD) is an inherited condition, caused by changes, or mutations, in the SERPINA1 gene, that can lead to lung disease and liver disease. There is a strong risk factor for emphysema in particular, and AATD is a common known genetic risk factor for this. It is caused by low levels of alpha-1 antitrypsin in the blood, which is a protein made in the liver that usually protects the lungs.

Pi stands for protease inhibitor. Alpha-1 antitrypsin is a type of protein called a protease inhibitor, so Pi type is the type(s) of alpha-1 protein that your body (primarily in your liver) makes. A Pi type is represented by two letters (such as MM, MZ, MS, ZZ). A Pi type is determined by a laboratory method called isoelectric focusing. In most cases your Pi type and your genetic type are the same. You can ask your doctor, genetic counselor, or contact the Alpha-1 Foundation’s genetic counselor at 1-800-785-3177 if you have questions about finding out your Pi type or what your Pi type means. Genetic counselors can be found on the National Society of Genetic Counselors website.

If you receive a liver transplant from a donor without alpha-1 antitrypsin deficiency (AATD), your new liver will make normal levels of alpha-1 antitrypsin (AAT) protein. This means that the level of AAT in your body should no longer be low. A liver transplant will not reverse any lung damage that has already occurred. If a living donor, such as a family member, is your donor, it is important to test them for AATD before the donation happens. Although a liver transplant cures a person’s low AAT levels, a liver transplant is a serious surgery that requires medications for life to combat rejection. Liver transplantation is a last treatment option for people who need it.

Alpha-1 antitrypsin deficiency (AATD) is caused by changes, or mutations, in the SERPINA1 gene. These lead to very low level of the alpha-1 antitrypsin protein in the blood. Alpha-1 antitrypsin protein is made in the liver and usually protects the lungs. AATD is inherited in an autosomal recessive manner, so people with the condition have mutations in both copies of their SERPINA1 gene. There are different versions, or alleles, of the SERPINA1 gene (also called "PI" types). The most common allele is the "M" allele, and having two of these leads to the usual amount of alpha-1 antitrypsin in the blood and no symptoms of AATD. The "S" allele leads to medium-low levels of alpha-1 antitrypsin protein. The "Z" allele leads to very low levels of alpha-1 antitrypsin protein. Having two copies of the Z allele leads to more symptoms of AATD. AATD carriers are those who have a mutation in one copy of their SERPINA1 gene (usually PI type "MZ").

Only blood testing can determine if someone has alpha-1 antitrypsin deficiency (AATD). A medical exam alone cannot determine whether someone has AATD. Additionally, some people who have changes, or mutations, in the gene for AATD (called SERPINA1) stay healthy for some or all of their lives. Genetic testing requires a blood sample, which may be taken by a finger stick or by a standard blood draw. The laboratory will do one or more of the following tests on your blood sample:

Your AAT level, or estimated AAT level, is the amount of alpha-1 antitrypsin protein in your blood. Alpha-1 antitrypsin deficiency (AATD) is classically defined as having an AAT level lower than 57 mg/dL or 11uM; however, there are variant forms where someone’s AAT level may actually be higher, but it is not working well. AAT is an acute phase reactant protein, which means the levels tends to go up when the body has inflammation, infection, or during a pregnancy. It is normal for someone’s AAT level to vary within the range for their genetic type of AATD. In most cases, you shouldn’t need to have regular AAT level measurements taken. An AAT level alone is not enough to confirm if someone is an AATD carrier. In those situations, genetic testing is needed.

A variant of unknown significance (VUS) means that, from genetic testing, there is a change in spelling of the DNA in your SERPINA1 gene. This is the gene associated with alpha-1 antitrypsin deficiency (AATD). However, but it is not known yet whether that DNA variant causes AATD in people or not. Some DNA variants are harmless and do not cause disease, such as those that cause eye color or hair color changes. If you have been found to have a VUS from genetic testing, check back with your doctor or genetic counselor later to see if more information becomes known. As DNA variants are better understood over time and scientists find more people with them, your variant may be reclassified and your result may have a clearer meaning.

A person can inherit alpha-1 antitrypsin deficiency (AATD) if both of their parents carry a change, or mutation, in the SERPINA1 gene. Their parents, AATD carriers, may not have symptoms of AATD. As such, AATD carriers not usually know they carry a gene with a mutation in it. Genetic testing can help sort this out, and there are medical recommendations for who should consider genetic testing for AATD. If you want to learn whether genetic testing for AATD may be right for you or your family member, speak to your healthcare provider about a referral to see a genetic counselor near you. In the U.S., the Alpha-1 Foundation provides free telephone-based genetic counseling and you can reach this service by calling 1-800-785-3177. Genetic counselors can be found on the National Society of Genetic Counselors website.

The main symptoms of alpha-1 antitrypsin deficiency (AATD) involve lung and liver disease, and these can vary from person to person. AATD can be tricky to diagnose because these signs and symptoms can be part of other conditions as well. Lung disease signs and symptoms in someone with AATD can include:

After a diagnosis of alpha-1 antitrypsin deficiency (AATD) is made, the following are recommended:

All mutations for alpha-1 antitrypsin deficiency (AATD) occur in the SERPINA1 gene. A person’s risk for symptoms of AATD depends on both copies of their SERPINA1 gene.

There are different versions, or alleles, of the SERPINA1 gene (also called "PI" types) that cause alpha-1 antitrypsin deficiency (AATD). The most common version or allele is the "M" allele, and having two of these leads to the usual amount of alpha-1 antitrypsin in the blood, which does not cause symptoms. The "S" allele leads to medium-low levels of alpha-1 antitrypsin protein. The "Z" allele leads to very low levels of alpha-1 antitrypsin protein. Having two copies of the Z allele leads to more symptoms of AATD and is the largest risk factor for liver disease, which can include cirrhosis or liver cancer. Risk for liver disease may also be increased by obesity, alcohol use, and a family history of AATD.

There are many different mutations in the SERPINA1 gene, which is associated with alpha-1 antitrypsin deficiency (AATD). Null mutations result in no alpha-1 antitrypsin (AAT) protein being produced. Null mutations result in great reduction of AAT in the blood and an increased risk for lung disease. Null mutations do not raise the risk for liver disease. Sequencing of the SERPINA1 gene by genetic testing is needed to fully define null mutations in each situation.

Smoking is the biggest risk factor for chronic obstructive pulmonary disease (COPD) in all people. Smoking makes COPD more likely to occur, and occur earlier, in people with alpha-1 antitrypsin deficiency (AATD). If you have been found to have alpha-1 antitrypsin deficiency and smoke, talk with your doctor about strategies to quit. Strategies may include medications and cessation support. People who are MZ carriers for alpha-1 antitrypsin deficiency are also at higher risk for COPD if they smoke.

There are treatments for people with alpha-1 antitrypsin deficiency (AATD). Guidelines written for healthcare providers about diagnosis and management of people with AATD can be found at: http://journal.copdfoundation.org/jcopdf/id/1115/The-Diagnosis-and-Management-of-Alpha-1-Antitrypsin-Deficiency-in-the-Adult

Augmentation therapy is the U.S. FDA-approved treatment for AATD-related lung disease. Augmentation therapy increases the amount of alpha-1 antitrypsin protein (AAT) in the blood and lungs. It is not meant for individuals with AATD who do not have lung disease. It does not treat liver disease. The goal is to slow or stop the progression of lung damage by replacing the protein that is missing. Augmentation therapy cannot cure AATD or restore lost lung function; however, there is evidence that it slows progression of emphysema.

Augmentation therapy is made of AAT protein from the blood of healthy human donors. It is usually given weekly by intravenous (IV) infusion. Infusions may be done at home or at an infusion center. Until other therapies become available, augmentation therapy is considered ongoing and lifelong.

As of 2017, there are four augmentation therapy products approved by the FDA and available in the United States: Prolastin-C, Aralast NP, Zemaira, and Glassia.

Augmentation therapy is the only specific therapy for AATD-related lung disease, but people with this also benefit from standard treatments for chronic obstructive pulmonary disease (COPD). If you have COPD due to AATD, talk with your healthcare provider about which treatments might be right for you.

There are many medications that treat symptoms of lung disease. In general, these medications are the same as those for individuals with other lung diseases, such as asthma, emphysema, bronchiectasis, and COPD. Medications may be taken by mouth or inhaled. Pills and capsules have an effect on the body as a whole, whereas inhaled medications target the lung directly.

Medications for lung disease may be prescribed to help decrease mucus production and inflammation, reduce or prevent flare-ups, open airways, help clear mucus, relieve air from being trapped in the lungs, help with airflow and fight infection.

People with AATD should receive vaccinations for influenza, pneumonia, whooping cough (pertussis), and hepatitis B.

People with COPD may require supplemental oxygen. Pulmonary rehabilitation programs help people to live and breathe better with the lung function they have.

Lung or liver transplantation is an option for some patients with advanced AATD. Individuals must have extensive damage to the lungs or liver to warrant this surgical option.

Next steps: For more information about treatments, talk to your doctor or someone who specializes in alpha-1 antitrypsin deficiency. A list of alpha-1 specialists can be found at www.alpha1.org.

As of May 2019, alpha-1 antitrypsin deficiency (AATD) is not currently a condition on routine newborn screening tests in the U.S. Talk with your healthcare provider if there is a reason, such as family history or symptoms, that you would like to consider testing your newborn for AATD.

As of 2017, newborn testing/screening is not available in the U.S. for alpha-1 antitrypsin deficiency (AATD). Talk with your healthcare provider if there is a reason, such as family history or symptoms, that you would like to consider testing your newborn for AATD.

Testing for alpha-1 antitrypsin deficiency (AATD) can happen in different ways. A diagnosis can be made by measuring the level of the alpha-1 antitrypsin (AAT) protein in someone’s blood. In people with AATD, this is much lower than usual. Specialized testing, called biochemical testing or PI typing, looks at the AAT protein forms in detail to determine if someone has AATD. Genetic testing at genetic testing laboratories can also study the sequence (spelling) of the DNA that make up the SERPINA1 gene, which is associated with AATD. This can find about 95% of people with AATD. People with AATD have two mutations in the SERPINA1 gene, one in each of their gene copies. Genetic testing can also find AATD carriers, who only have a mutation in one copy of their SERPINA1 genes.

If you want to learn whether genetic testing for AATD may be right for you or your family member, speak to your healthcare provider about a referral to see a genetic counselor near you. In the U.S., the Alpha-1 Foundation provides free telephone-based genetic counseling and you can reach this service by calling 1-800-785-3177. Genetic counselors can be found on the National Society of Genetic Counselors website.

The Alpha-1 Foundation and Medical University of South Carolina also make free and confidential testing available for alpha-1 antitrypsin deficiency. This free testing is part of a research study called the Alpha-1 Coded Testing (ACT) Study. Participants receive a free, at-home test kit after completing an informed consent form and research questionnaire. Results are returned directly to the participant several weeks later. For more information, or to join the ACT Study for a free test kit, visit www.alphaoneregistry.org.

As of 2017, the Alpha-1 Foundation and Medical University of South Carolina make free and confidential testing available for alpha-1 antitrypsin deficiency. This free testing is part of a research study called the Alpha-1 Coded Testing (ACT) Study. Participants receive a free, at-home test kit after completing an informed consent form and research questionnaire. Results are returned directly to the participant several weeks later. For more information, or to join the ACT Study for a free test kit, visit www.alphaoneregistry.org.

There are also free test kits available to healthcare providers to use in their clinical practice. These kits must be requested from the companies who offer them. Each company that makes an augmentation product for the treatment of alpha-1 antitrypsin deficiency also offers free testing for the condition. More information can be found at www.alpha1.org.

Although there are treatments, as of May 2019 there is no cure for alpha-1 antitrypsin deficiency.

Genetic carrier screening for alpha-1 antitrypsin deficiency (AATD) is possible during pregnancy. AATD is a condition included on some expanded carrier screens. Expanded carrier screening is an option during pregnancy but it is not standard of care, so many pregnant women do not have carrier screening for AATD or other conditions on these tests. If you are interested in prenatal carrier screening, speak to your healthcare provider about a referral to see a genetic counselor near you. In the U.S., the Alpha-1 Foundation provides free telephone-based genetic counseling and you can reach this service by calling 1-800-785-3177. Genetic counselors can be found on the National Society of Genetic Counselors website.

Prenatal diagnosis (genetic testing) by the amniocentesis or chorionic villus sampling (CVS) procedures is possible for alpha-1 antitrypsin deficiency (AATD). This can happen when the parents of the baby have had genetic testing and their SERPINA1 gene mutations are known, which means the baby is known to be at risk for AATD. Anyone interpreting abnormal prenatal genetic results should be cautious, because abnormal genetic results cannot usually predict how mild or severe the AATD will be in the baby or child. One exception is that babies with the ZZ genetic makeup, who have had a sibling with severe liver disease and the same ZZ gene makeup, have a higher risk to also have severe liver disease.

Most women with alpha-1 antitrypsin deficiency (AATD) have normal pregnancies. Because the condition is under-recognized, and because symptoms often first occur after usual childbearing years, many women with AATD do not know that they have it when they become pregnant. If you know you have AATD and are considering pregnancy, talk with your doctor about any specific recommendations. AATD genetic testing for your reproductive partner can usually help you learn whether there is a risk for AATD in the baby. You may want to contact a genetic counselor to discuss prenatal testing. Genetic counselors can be found on the National Society of Genetic Counselors website.

Exercise helps people achieve a healthy body composition, which is good for lung and liver health and general well-being. It is recommended that you speak with your personal physician before beginning a new exercise program.

Augmentation therapy for people with alpha-1 antitrypsin deficiency (AATD) is not recommended for individuals with the MZ genotype (or other carrier genotypes), individuals with AATD-related lung disease who continue to smoke, individuals with AATD and emphysema or bronchiectasis who do not have airflow obstruction, for the treatment of AATD liver disease, or for those who have undergone liver transplantation.

Medical guidelines can be found at http://journal.copdfoundation.org/jcopdf/id/1115/The-Diagnosis-and-Management-of-Alpha-1-Antitrypsin-Deficiency-in-the-Adult

Talk with your doctor and transplant team. There are controversial opinions about the use of augmentation therapy for people with alpha-1 antitrypsin deficiency (AATD) after lung transplantation. In one rationale, the length of time (usually decades) that it takes for alpha-1 lung disease to develop is longer than most people are expected to live post-transplant. It is unlikely that the transplanted lungs would ever develop AATD-related lung disease. In another rationale, the recipient with AATD still has the deficiency and augmentation therapy may be continued to promote an optimal condition for the lungs. Anti-inflammatory properties of alpha-1 antitrypsin may also support its use in people post-transplant, but more research is needed.

If you have received a new liver through liver transplantation, the liver will make alpha-1 antitrypsin normally (as long as it is from an unaffected donor). Augmentation therapy will no longer be needed.

Alpha-1 antitrypsin deficiency (AATD) has many genetic forms:

MM: This is the normal alpha-1 antitrypsin deficiency genotype. About 92% of Caucasians are genotype MM. Individuals with MM have no increased risk for AATD-related disorders and no increased risk to relatives.

MZ, MS, M-Other: These are AATD carriers and they may have a mild deficiency. All parents, children, and full siblings of AATD carriers also have a 50% risk to be carriers. Genetic testing should be considered for these family members. Based on family or medical history, some people in the family may have an increased risk for severe AATD.

SS: This genotype is associated with an intermediate alpha-1 antitrypsin protein levels. A person’s risk for lung disease may be mildly increased and smoking should be avoided. Risks for liver disease are not increased.

SZ: This genotype causes a moderate to severe deficiency of alpha-1 antitrypsin protein levels and an increased risk for AATD-related lung disease. Risk for liver disease is somewhat increased. Your specific risks and symptoms should always be discussed with a trained medical professional. See http://alpha-1foundation.org/clinical-resource-centers/ to find a specialist near you.

Your parents and children are "obligate carriers" of either the S or the Z. Carriers may wish to know this for lifestyle planning, healthcare management and reproductive decision making. Testing should be considered. Risk for a given individual to be more severely affected depends on the genotypes of both of their parents. It uncommon for multiple generations of a family to be severely affected (SZ, ZZ), though this can occur.

Your full siblings are at-risk to have the SZ genotype, as well. They may also be Alpha-1 carriers or unaffected and not a carrier. Testing is recommended.

ZZ: This genotype causes a severe deficiency and significantly increased risk for alpha-1 lung disease in adults. Risk for liver disease is also increased in infants and adults. Severe liver disease affects a small portion of infants with the ZZ genotype. Your specific risks and symptoms should always be discussed with a trained medical professional. See http://alpha-1foundation.org/clinical-resource-centers/ to find an alpha-1 specialist near you.

For those with the ZZ genotype, parents and children are "obligate carriers" of the Z allele. Carriers may wish to know this for lifestyle planning, healthcare management and reproductive decision making. Genetic testing should be considered. Risk for a given individual to be more severely affected depends on which genotypes both of their parents have. It uncommon for multiple generations of a family to be severely affected (SZ, ZZ), though rarely this can occur.

For those with the ZZ genotype, full siblings are at risk to have the ZZ genotype and symptoms of AATD as well. They may also be AATD carriers or unaffected, and not a carrier. Genetic testing is recommended for them to consider.

If you have questions, or have another alpha-1 genotype not discussed above, call the Alpha-1 Foundation genetic counselor in the U.S. at 1-800-785-3177.

Everyone has two copies of the gene associated with alpha-1 antitrypsin deficiency (AATD), which is called SERPINA1. We inherit our genes from our parents and pass them to our children. A person can inherit alpha-1 antitrypsin deficiency (AATD) if both of their parents carry a change, or mutation, in the SERPINA1 gene. Their parents, called AATD carriers, may not have symptoms of AATD themselves.

Carriers have one SERPINA1 gene with a mutation and one copy without it. If two AATD carriers have children together, they have a 25% (1 in 4) chance to have a child with AATD in each pregnancy. People with AATD have two SERPINA1 mutations — one in each copy of their gene. This is also called autosomal recessive inheritance, which happens equally in males and females. Any child of an AATD carrier also has a 50% chance to be a carrier, too, just like their parents. Full siblings of someone with AATD are also at risk to have the condition and should be tested.

There are different versions, or alleles, of the SERPINA1 gene (also called "PI" types). The most common allele is the "M" allele, and having two of these leads to the usual amount of alpha-1 antitrypsin in the blood and no symptoms of AATD. The "S" allele leads to medium-low levels of alpha-1 antitrypsin protein. The "Z" allele leads to very low levels of alpha-1 antitrypsin protein. Having two copies of the Z allele leads to more symptoms of AATD.

AATD carriers are those who have a mutation in one copy of their SERPINA1 gene (usually PI type "MZ" but can be "MS" or "M-Other"). Most carriers do not develop symptoms of AATD. However, recent research has shown that AATD carriers who smoke are at high risk to develop lung disease. Some AATD carriers may also have a small increased risk for liver disease. Carriers should avoid smoking and live a healthier lifestyle.

The following testing may be performed to help diagnose chronic obstructive pulmonary disease:

You can get tested for alpha-1 antitrypsin deficiency (AATD) in different ways. A diagnosis can be made by measuring the level of the alpha-1 antitrypsin (AAT) protein in someone’s blood. In people with AATD, this is much lower than usual. Specialized testing, called biochemical testing or PI typing, looks at the AAT protein forms in detail to determine if someone has AATD. Genetic testing can also study the sequence (spelling) of the DNA that make up the SERPINA1 gene, which is associated with AATD. This can find about 95% of people with AATD. People with AATD have two mutations in the SERPINA1 gene, one in each of their gene copies. Genetic testing can also find AATD carriers, who only have a mutation in one copy of their SERPINA1 genes.

Medical recommendations have been made about who should be tested for AATD, which include:

As of 2019, there are ongoing research studies to learn more about alpha-1 antitrypsin deficiency (AATD) and develop better treatments. People with genetically confirmed AATD are invited to join the Alpha-1 Research Registry at www.alphaoneregistry.org. The Research Registry is a contact registry for people affected by AATD, and invites members to participate in trials as they come up. You can also view ongoing studies on that site, or at the ClinicalTrials.gov website at www.clinicaltrials.gov.

If you have not had genetic testing, as of 2017 the Alpha-1 Foundation and Medical University of South Carolina also make free and confidential testing available for alpha-1 antitrypsin deficiency. This free testing is part of a research study called the Alpha-1 Coded Testing (ACT) Study. Participants receive a free, at-home test kit after completing an informed consent form and research questionnaire. Results are returned directly to the participant several weeks later. For more information, or to join the ACT Study for a free test kit, visit www.alphaoneregistry.org.

Alpha-1 antitrypsin deficiency (AATD) is likely an under-recognized genetic condition that can cause lung disease and liver disease. Symptoms can vary from person to person and be difficult to diagnose. The first signs of lung disease usually happen between ages 20-50 years of age. Smoking is a major risk factor for lung disease in people with the condition. AATD can cause emphysema, which can progress to chronic obstructive pulmonary disease (COPD) faster in smokers. The prevalence of AATD varies significantly from country to country and it is more common in people of northern European heritage. As of 2017, it occurs in about 1 in 5,000-7,000 North Americans and 1 in 1,500-3,000 Scandinavians. It is seen much less often in people of Asian heritage. Different changes, or mutations, in the SERPINA1 gene are associated with AATD, and combinations of these usually cause different symptoms in people.

You can ask your doctor or genetic counselor to order genetic testing for alpha-1 antitrypsin deficiency (AATD). You can find a genetic counselor near you in the U.S. by using the Find a Genetic Counselor search tool on the National Society of Genetic Counselors’ website. The Alpha-1 Foundation also has a genetic counselor who can help understand your testing options and results. This is a free and confidential service in the U.S. Call 1-800-785-3177 to speak with the alpha-1 genetic counselor.

As of 2017, the Alpha-1 Foundation and Medical University of South Carolina also make free and confidential testing available for alpha-1 antitrypsin deficiency. This free testing is part of a research study called the Alpha-1 Coded Testing (ACT) Study. Participants receive a free, at-home test kit after completing an informed consent form and research questionnaire. Results are returned directly to the participant several weeks later. For more information, or to join the ACT Study for a free test kit, visit www.alphaoneregistry.org.

Smoking is a known risk factor for lung disease in people with alpha-1 antitrypsin deficiency (AATD). People who smoke can develop lung disease like chronic obstructive pulmonary disease (COPD) decades earlier, such as between 40-50 years of age, instead of decades later in non-smokers (who may not get COPD at all). Other environmental factors that may contribute to earlier or more severe symptoms include secondhand smoke, workplace exposures to dusts, fumes and pollutants, mineral dust, gas, and everyday exposures to air pollution or particles. Getting diagnosed early and avoiding risk factors, like smoking, can keep people with AATD healthy their entire lives.

Other lifestyle factors may affect symptoms of AATD. Maintaining a healthy body weight and composition is important for people who have, or are at risk for, lung or liver disease. This can be achieved through diet with exercise. If alcohol is used, it should be in moderation. People with AATD are encouraged to talk with a healthcare provider that is informed about AATD about their personal recommendations.

Some people with alpha-1 antitrypsin deficiency (AATD) have no symptoms for some or all of their lives. The chance that someone will get symptoms depends on their AATD genetic makeup and their lifestyle habits, such as smoking. AATD is caused by changes, or mutations, in the SERPINA1 gene. AATD is inherited in an autosomal recessive manner, so people with the condition have mutations in both copies of their SERPINA1 gene. There are different versions, or alleles, of the SERPINA1 gene (also called "PI" types). The most common allele is the "M" allele, and having two of these leads to the usual amount of alpha-1 antitrypsin in the blood and no symptoms of AATD. The "S" allele leads to medium-low levels of alpha-1 antitrypsin protein. The "Z" allele leads to very low levels of alpha-1 antitrypsin protein. People with "SZ" alleles can have some symptoms of AATD. Having "ZZ" alleles leads to more symptoms of AATD. AATD carriers are those who have a mutation in one copy of their SERPINA1 gene (usually "MZ" alleles).

Not all airlines allow portable oxygen concentrators (POC) on the plane, but some do. Check with your airline and the manufacturer of your POC to determine whether it is approved for flight. The Alpha-1 Foundation also offers resources about traveling with oxygen at www.alpha1.org.

Home infusions are possible for most people receiving augmentation therapy to treat their alpha-1 antitrypsin deficiency. This may depend on your health insurance coverage and availability of home infusion service near you. Talk to your physician or specialty pharmacy about your infusion options.

The same signs and symptoms that occur in alpha-1 antitrypsin deficiency (AATD) can happen for non-genetic or other genetic reasons. However, in those situations they are not due to AATD. All of AATD is due to mutations in the SERPINA1 gene.

As of May 2019, there are many ongoing clinical trials and research studies to learn more about and develop better treatments for alpha-1 antitrypsin deficiency (AATD).

People with genetically confirmed AATD are invited to join the Alpha-1 Research Registry at www.alphaoneregistry.org. The Research Registry is a contact registry for people affected by AATD, and invites members to participate in trials as they come up. You can also view ongoing studies on that site, or at the ClinicalTrials.gov website at www.clinicaltrials.gov.

Other names for alpha-1 antitrypsin deficiency include AATD, AAT, alpha-1 protease inhibitor deficiency, alpha-1 related emphysema, genetic emphysema, hereditary pulmonary emphysema, and inherited emphysema.

The health complications for people with alpha-1 antitrypsin deficiency AATD, like chronic obstructive pulmonary disease (COPD), breathing problems, and liver disease, can occur for many reasons. In fact, doctors cannot usually tell by your symptoms alone wither or not you have AATD. Many people with AATD are first diagnosed with asthma or other conditions, and a majority of people living with the condition have not been diagnosed. COPD can occur due to cigarette smoking or a combination of other genetic and environmental factors. Liver cirrhosis can occur due to other genetic diseases, contributions of diet, obesity or alcohol use, or a combination of genetic and environmental factors. Medical recommendations outline who should have testing for AATD. For example, they suggest that anyone with COPD or unexplained liver disease should be tested for AATD.

If you suspect you, your family member, or someone you know has AATD, talk to your doctor about testing.

Everyone with alpha-1 antitrypsin deficiency (AATD) has mutations in the gene called SERPINA1, but different mutations in the gene lead to different forms of AATD. For example, some mutations cause an increased risk for liver disease and others do not. The combination of mutations also determine how high the risk is for lung disease.

The SERPINA1 gene normally makes a protein called alpha-1 antitrypsin (AAT). AAT is a type of protein called a protease inhibitor (Pi). Normal AAT is called "M" (Pi M). Mutations in the SERPINA1 gene are named according to their abnormal AAT product. The "Z" mutation makes an abnormal AAT protein called "Z" (Pi Z). ZZ (PiZZ) alpha-1 is the most common form of AATD that is clinically diagnosed and people with this have the most severe symptoms. This happens when someone has two "Z" mutations.

Rarely, people with alpha-1 antitrypsin deficiency (AATD) develop an inflammation of the panniculus, which is called panniculitis. The panniculus is a layer of fatty and fibrous tissue just beneath the skin. Panniculitis can look like a honeycomb of raised red spots on the skin, and can also look like other things (like lupus, rheumatoid arthritis, and reactions to some medications). Panniculitis can be very painful. It can be treated with steroids, antibiotics, and completely exchanging the body’s blood plasma. People with AATD can also have augmentation therapy, which are intravenous (IV) infusions of donated alpha-1 protein.

As of 2019, there are over 80 support groups in the U.S. for people with alpha-1 antitrypsin deficiency. You can locate a support group at https://www.alpha1.org/Alphas-Friends-Family/Support/Support-Groups . There are also virtual support groups through the Alpha-1 Foundation. Individual support groups may vary. In general, support groups help people affected by alpha-1 to connect with others, learn more about the condition, raise awareness and funds, and provide emotional support.

The Alpha-1 Foundation is committed to finding a cure for alpha-1 antitrypsin deficiency (AATD) and to improving the lives of people affected by the condition worldwide. The Alpha-1 Foundation provides numerous services and support organizations for people affected by alpha-1 and maintains a network of alpha-1 specialty centers. Visit www.alpha1.org.

The Alpha-1 Research Registry, Alpha-1 Coded Testing Study and more information about the Alpha-1 Foundation Genetic Counseling Program can be found at www.alphaoneregistry.org.

AlphaNet is devoted to improving the lives of individuals with Alpha-1 through comprehensive disease management services, clinical research administration and consultative services. Visit www.alphanet.org. AlphaNet’s Big Fat Reference Guide (BFRG) is a comprehensive guide and self-management program available on the Internet for individuals living with Alpha-1. Visit www.alphanetbfrg.org.

The COPD Foundation provides patients and families with information on COPD, treatment resources, support programs and an advocacy center. Visit www.copdfoundation.org.