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Alpha-1 Antitrypsin Deficiency

Other Names: Alpha-1 Protease Inhibitor Deficiency, Inherited Emphysema, Genetic Emphysema


Alpha-1 Antitrypsin Deficiency is a genetic condition that can cause lung disease and liver disease. It is caused by mutations in the SERPINA1 gene that makes the alpha-1 antitrypsin protein.

Characteristics of Alpha-1 Antitrypsin Deficiency
Alpha-1 Antitrypsin Deficiency (AATD) is a largely under-recognized genetic condition that predisposes to obstructive lung disease in adults, and liver disease in infants, children and adults. It affects approximately 1 in 2,000 to 1 in 5,000 individuals. Alpha-1 antitrypsin is a protein primarily produced by the liver that protects lung tissue from an enzyme called neutrophil elastase. This enzyme gets released during periods of inflammation. When there is not enough alpha-1 antitrypsin in the lungs, this increases the risk for chronic obstructive pulmonary disease (COPD). COPD includes emphysema and chronic bronchitis. Cigarette smoking and occupational exposures are risk factors for COPD. In addition, AATD is associated with bronchiectasis and asthma that is not completely reversible with treatment.
Most individuals with AATD produce alpha-1 antitrypsin protein in the liver that is shaped incorrectly. This can cause the abnormally shaped protein to build up in liver cells and damage them. This damage can present as cirrhosis, chronic hepatitis and/or liver cancer. Other less common features of AATD include vasculitis (inflammation of blood vessels) and a rare skin condition called panniculitis.

Diagnosis/Testing
Alpha-1 Antitrypsin Deficiency (AATD) is a largely under-recognized genetic condition that predisposes to obstructive lung disease in adults, and liver disease in infants, children and adults. It affects approximately 1 in 2,000 to 1 in 5,000 individuals. Alpha-1 antitrypsin is a protein primarily produced by the liver that protects lung tissue from an enzyme called neutrophil elastase. This enzyme gets released during periods of inflammation. When there is not enough alpha-1 antitrypsin in the lungs, this increases the risk for chronic obstructive pulmonary disease (COPD). COPD includes emphysema and chronic bronchitis. Cigarette smoking and occupational exposures are risk factors for COPD. In addition, AATD is associated with bronchiectasis and asthma that is not completely reversible with treatment.
Most individuals with AATD produce alpha-1 antitrypsin protein in the liver that is shaped incorrectly. This can cause the abnormally shaped protein to build up in liver cells and damage them. This damage can present as cirrhosis, chronic hepatitis and/or liver cancer. Other less common features of AATD include vasculitis (inflammation of blood vessels) and a rare skin condition called panniculitis.

Management/Surveillance
Individuals with AATD have an increased risk to develop lung and/or liver disease due to environmental and occupational exposures. Individuals that have one or two mutations in the SERPINA1 gene need to avoid cigarette smoke as well as secondhand smoke. It is also recommended that individuals with AATD avoid careers in unclean air environments, such as exposures to dust and pollution. Management of AATD lung disease includes all of the typical medications and treatments for COPD, asthma, and bronchiectasis. In addition, for individuals with AATD and lung disease, augmentation therapy may be recommended. Augmentation therapy is typically a once a week IV infusion of alpha-1 antitrypsin protein that has been separated from human pooled plasma. It is intended to raise the level of alpha-1 antitrypsin in the blood and lungs. For individuals with severely decreased lung function, lung transplantation may be recommended.
At this time there is no specific treatment for AATD liver disease. Instead, treatment focuses on managing symptoms. Individuals with liver failure may be candidates for liver transplantation. Individuals with AATD should avoid injuries to the liver such as from excessive alcohol consumption, fatty liver disease and hepatitis. At this time, liver transplantation is the only known “cure” for AATD.
Due to the increased risk of liver and lung disease, it is recommended that individuals with AATD receive the flu vaccine every year as well as the pneumococcal and hepatitis vaccines.
Not everyone with the genetic mutation(s) for AATD will develop symptoms. The age of onset and severity are largely modified by environmental exposures that have occurred throughout the person’s lifetime. Those with no current symptoms should have baseline pulmonary function testing and liver function testing and follow the recommendations of their physician for monitoring.

Mode of inheritance
AATD is inherited in an autosomal codominant pattern. Codominant inheritance is when both copies of a gene are expressed even in the presence of the other. In AATD, this means that both copies of the SERPINA1 gene are expressed and produce the corresponding protein. For example, the Z allele produces the Z protein, and the S allele produces the S protein. For individuals that have two mutations, such as the S and Z alleles, their liver produces both S and Z proteins.

Risk to family members
For individuals that have two mutations, such as the S and Z alleles, they inherited the S allele from one parent, and the Z allele from the other parent.

Special considerations
None

Resources
Alpha-1 Association
Alpha-1 Foundation
AlphaNet
Alpha-1 Kids
Genetics Home Reference: Alpha-1 Antitrypsin Deficiency
Learn.Genetics: Alpha-1 Antitrypsin Deficiency

References
American Thoracic Society, European Respiratory Society. (2003)."American Thoracic Society/European Respiratory Society Statement: Standards for the Diagnosis and Management of Individuals with Alpha-1 Antitrypsin Deficiency." American Journal of Respiratory and Critical Care Medicine 168(7): 818-900.
Schlade-Bartusiak K, Cox DW. (Updated 27 October 2006). Alpha1-Antitrypsin Deficiency. In: GeneReviews at GeneTests Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2013. Available at http://www.ncbi.nlm.nih.gov/books/NBK1519/. Accessed [04/17/2013].
Stoller, JK. et al. (2012)."A review of _1-antitrypsin deficiency." American Journal of Respiratory and Critical Care Medicine 185(3): 246-259.

Created:04/2013

Updated:mm/yyyy

Created by:Dawn McGee, MS, CGC (Grifols Inc.), Sara Wienke, MS, CGC (MUSC)

Edited by:Seema Jamal, MSc, LCGC



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