Alpha-1-antitrypsin deficiency

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).

The risk for lung disease in alpha-1 antitrypsin deficiency (AATD) increases with age. The lifetime risk for emphysema in people with SZ alleles is estimated to be 20-50%. The lifetime risk for emphysema in people with ZZ alleles is estimated to be 80% or higher. The risk for liver disease is highest in people with ZZ alleles. Up to 40% of infants with ZZ alleles may have abnormal liver function; however 2.4% of these infants experience life-threatening liver disease that may be treated by liver transplantation or result in death. Liver disease is less common in older children and young adults. 10-40% of adults over the age of 40 with ZZ alleles will have liver disease to a varying degree. This is usually liver cirrhosis, and hepatocellular carcinoma (a liver cancer) is a rare complication. A few people with AATD, especially non-smokers, can live a normal length of life without developing symptoms of AATD.

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.

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.

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.