Alpha-1 antitrypsin deficiency
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
Age of Onset
Autosomal dominant ?A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease
Autosomal recessive ?Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype
X-linked dominant ?X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.
X-linked recessive ?Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder
Mitochondrial or multigenic ?Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.
Multigenic or multifactor ?Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.
Other Names (AKA)
AAT deficiency; A1AT deficiency; AATD;
Congenital and Genetic Diseases; Digestive Diseases; Kidney and Urinary Diseases;
Alpha-1 antitrypsin deficiency (AATD) is an
AATD is caused by changes (pathogenic variants, also called
This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.
|Medical Terms||Other Names||
|80%-99% of people have these symptoms|
|30%-79% of people have these symptoms|
Yellowing of the skin
[ more ]
|5%-29% of people have these symptoms|
Scar tissue replaces healthy tissue in the liver
|1%-4% of people have these symptoms|
|Percent of people who have these symptoms is not available through HPO|
|Chronic pulmonary obstruction||0006510|
|Elevated hepatic transaminase||
High liver enzymes
Genetic changes that cause AAT may mean that the body's liver
In addition, abnormal AAT can build up in the liver and cause damage to the liver, especially in people who have two copies of the specific genetic variant called
Confirming the diagnosis involves a blood test showing a low level the alpha-1 antitrypsin
- Detecting an AAT protein variant that does not work properly (functionally deficient) using a special test called isoelectric focusing.
- Finding a disease causing change (pathogenic variant, also called
mutation) in both copies of the SERPINA1 geneby genetic testing. (This confirms the diagnosis when the above-mentioned tests are not performed or their results are not in agreement.)
Specialists involved in the diagnosis may include primary care doctors, lung specialists (
Augmentation therapy aims to increase the blood level of alpha-1 antitrypsin
- Are older than 18 years of age.
- Have levels of alpha-1 antitrypsin in blood that are less than 11 micromoles/liter.
- Have pulmonary function tests (spirometer ) that show airway obstruction.
- Do not smoke or have stopped smoking for at least the last 6 months.
- Are willing to be get the infusions weekly at the hospital.
- Do not have immunoglobulin A deficiency, because the therapy with alpha-1 may contain traces of immunoglobulin type A (IgA), and patients with IgA deficiency may have
- In some cases it is also done in people who have normal airflow, but who have a
CT scanthat shows emphysema in the lung. Antibioticsto treat infections.
- Bronchodilators and inhaled steroids can help open the airways and make breathing easier.
- Exercise program.
- Lung volume reduction surgery.
- Lung transplantation for patients with advanced emphysema due to severe AAT deficiency.
- Liver transplantation for patients with severe liver disease. After a liver transplant the AAT deficiency is corrected, because normal donor liver produces and secretes normal AAT.
- Vaccination against hepatitis A and B.
- Preventive vaccines against influenza and pneumococcal vaccines.
- Avoid using tobacco.
- Avoid or minimize drinking alcohol (for those at risk for liver disease).
- Avoid other environmental
risk factorssuch as chemical exposures.
- Liver function tests periodically for people with two copies of the Z
- Lung function test every six to 12 months people with severe AATD.
ultrasound, in cases of liver disease, every 6 to 12 months to monitor for fibrotic changes (cirrhosis) and liver cancer(hepatocellular carcinoma).
- Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.
The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.
- Alpha1-Proteinase Inhibitor (Human)(Brand name: Prolastin) Manufactured by Grifols United States
FDA-approved indication: For chronic replacement therapy of individuals having
congenitaldeficiency of alpha1proteinase inhibitor with clinically demonstrable panacinar emphysema.
National Library of Medicine Drug Information Portal
Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.
Alpha-1 Antitrypsin Deficiency Canada Inc. (Alpha-1 Canada)
13300 Tecumseh Road East, Suite #241
Tecumseh, ON, N8N 4R8 Canada
American Liver Foundation
39 Broadway, Suite 2700
New York, NY 10006
Toll-free: +1-800-465-4837 (Helpline)
These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.
- MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
- Genetics Home Reference (GHR) contains information on Alpha-1 antitrypsin deficiency. This website is maintained by the National Library of Medicine.
- The National Heart, Lung, and Blood Institute (NHLBI) has information on this topic. NHLBI is part of the National Institutes of Health and supports research, training, and education for the prevention and treatment of heart, lung, and blood diseases.
- The National Human Genome Research Institute's (NHGRI) website has an information page on this topic. NHGRI is part of the National Institutes of Health and supports research on the structure and function of the human genome and its role in health and disease.
- The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
- GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
- Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
- The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
- Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
- Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
- PubMed is a searchable database of medical literature and lists journal articles that discuss Alpha-1 antitrypsin deficiency. Click on the link to view a sample search on this topic.
- Sandhaus RA, Turino G, Brantly ML, et al. The Diagnosis and Management of Alpha-1 Antitrypsin Deficiency in the Adult. Chronic Obstr Pulm Dis (Miami). 2016; 3(3):668-682.
- Stoller JK. Clinical manifestations, diagnosis, and natural history of alpha-1 antitrypsin deficiency. UpToDate. May 25, 2018; https://www.uptodate.com/contents/clinical-manifestations-diagnosis-and-natural-history-of-alpha-1-antitrypsin-deficiency.
- Stoller JK, Lacbawan FL, Aboussouan LS. Alpha-1 Antitrypsin Deficiency. GeneReviews. January 19, 2017; https://www.ncbi.nlm.nih.gov/books/NBK1519/.
- Stoller JA. Extrapulmonary manifestations of alpha-1 antitrypsin deficiency. UpToDate. May 23, 2018; https://www.uptodate.com/contents/extrapulmonary-manifestations-of-alpha-1-antitrypsin-deficiency.
- Alpha-1 antitrypsin deficiency. Genetics Home Reference. January 2013; https://ghr.nlm.nih.gov/condition/alpha-1-antitrypsin-deficiency.
- Stoller JK. Treatment of alpha-1 antitrypsin deficiency. UpToDate. April 20, 2018; https://www.uptodate.com/contents/treatment-of-alpha-1-antitrypsin-deficiency.
- Alpha-1 Antitrypsin Deficiency. National Heart, Lung, and Blood Institute (NHLBI). October 2011; https://www.nhlbi.nih.gov/health-topics/alpha-1-antitrypsin-deficiency.