The liver produces a protein called Alpha-1 Antitrypsin (A1AT), which circulates throughout the body. A1AT acts as a “protease inhibitor,” blocking the activity of proteases, which are enzymes that break down proteins. Its primary responsibility is to safeguard tissues, particularly those in the lungs, from damage caused by certain enzymes.
A1AT targets neutrophil elastase, an enzyme released by white blood cells during inflammation or infection. While neutrophil elastase helps the body fight off invaders by breaking down bacterial proteins, if its activity is not controlled, it can also harm healthy lung tissue. A1AT binds to neutrophil elastase, stopping it from causing excessive damage and maintaining the integrity of lung structures.
Understanding Alpha-1 Deficiency
Alpha-1 Antitrypsin Deficiency is a genetic condition inherited from parents, stemming from mutations in the SERPINA1 gene. This gene provides instructions for making the A1AT protein. When mutations occur in SERPINA1, the body either produces insufficient amounts of A1AT or creates a dysfunctional version of the protein.
The S and Z alleles are the most common variants associated with deficiency. Individuals inheriting two copies of the Z allele (ZZ genotype) have extremely low A1AT levels, which significantly raises their risk of developing related health problems. These reduced or impaired A1AT levels leave the body, especially the lungs, vulnerable to unchecked enzyme activity and subsequent tissue damage.
Effects on Health
The health consequences of Alpha-1 Antitrypsin Deficiency primarily affect the lungs and liver. In the lungs, the most common issues are emphysema and chronic obstructive pulmonary disease (COPD). Without enough functional A1AT, neutrophil elastase can excessively break down elastin, a protein that provides elasticity to lung tissue. This leads to irreversible damage to the small air sacs (alveoli). This damage results in symptoms such as shortness of breath, wheezing, and a persistent cough, often appearing between the ages of 25 and 50. Smoking significantly worsens lung damage in individuals with this deficiency.
Liver disease, including cirrhosis (scarring of the liver), can also occur, particularly in individuals with the Z allele, where abnormal A1AT proteins can accumulate in liver cells. Approximately 10% of infants with Alpha-1 Antitrypsin Deficiency develop liver disease, which may present as jaundice. In adults, about 15% may develop liver damage, increasing the risk of liver cancer. Less commonly, a skin condition called panniculitis, characterized by hardened, painful lumps, can develop.
Diagnosis and Management Approaches
Diagnosing Alpha-1 Antitrypsin Deficiency typically involves a blood test to measure A1AT levels. If levels are abnormally low, genetic testing, such as genotyping or phenotyping, is performed to identify the specific SERPINA1 gene mutations. Early diagnosis is important for managing the condition and can be achieved by testing all individuals with COPD, unexplained chronic liver disease, or necrotizing panniculitis. Family members of affected individuals should also be offered testing and genetic counseling.
Management strategies focus on preventing further tissue damage and alleviating symptoms. Augmentation therapy involves weekly intravenous infusions of A1AT protein, purified from healthy donor plasma, to increase A1AT levels in the lungs and blood. This therapy helps restore the protective anti-elastase capacity, slowing lung disease progression and reducing inflammation. Lifestyle modifications are also encouraged, such as avoiding smoking, which significantly accelerates lung damage, and limiting alcohol consumption to protect the liver. For specific organ damage, individuals may also receive standard treatments for conditions like COPD or liver disease.