The etiology is from mutations in the gene responsible for producing alpha-1 antitrypsin.
The gene for Alpha-1-antitrypsin is on chromosome 14.
The most common mutation is the PiZ allele.
It is expressed in the hepatocyte and in the mononuclear phagocyte.
Two parental alleles, Z type and S type, are codominantly expressed.
Phenotypes, null-null, ZZ, and SZ, are responsible for emphysema.
This condition is due to a mutation in the SERPINA1 gene that results in not enough alpha-1 antitrypsin (A1AT), a protein that protects your lungs12.
The onset of lung problems is typically between 20 and 50 years of age1. This may result in shortness of breath, wheezing, or an increased risk of lung infections1. Complications may include chronic obstructive pulmonary disease (COPD), cirrhosis, neonatal jaundice, or panniculitis1.
Risk factors for lung disease include tobacco smoking and environmental dust1. The underlying mechanism involves unblocked neutrophil elastase and buildup of abnormal A1AT in the liver1. It is autosomal co-dominant, meaning that one defective allele tends to result in milder disease than two defective alleles1.
The diagnosis is suspected based on symptoms and confirmed by blood tests or genetic tests2. Treatment of lung disease may include bronchodilators, inhaled steroids, and, when infections occur, antibiotics2. Intravenous infusions of the A1AT protein or in severe disease lung transplantation may also be recommended2. In those with severe liver disease, liver transplantation may be an option2.
Avoiding smoking is recommended2. Vaccination for influenza, pneumococcus, and hepatitis is also recommended2. Life expectancy among those who smoke is 50 years while among those who do not smoke it is almost normal1. The condition affects about 1 in 2,500 people of European descent1. Severe deficiency occurs in about 1 in 5,0001. In Asians, it is uncommon1. About 3% of people with COPD are believed to have the condition1.