Trait Document

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.

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.

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.

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.

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.

None