Alpha-1-antitrypsin deficiency

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.

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.

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.

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.