Alpha-1 antitrypsin deficiency

Alpha-1 antitrypsin deficiency (AATD) is caused by mutations in the SERPINA1 gene. This gene gives the body instructions to make a protein called alpha-1 antitrypsin (AAT), which protects the body from an enzyme called neutrophil elastase. Neutrophil elastase helps the body fight infections, but it can also attack healthy tissues (especially the lungs) if not controlled by AAT.

Mutations that cause AAT can cause a deficiency or absence of AAT, or a form of AAT that does not work well. This allows neutrophil elastase to destroy lung tissue, causing lung disease. In addition, abnormal AAT can build up in the liver and cause damage to the liver.

The severity of AATD may also be worsened by environmental factors such as exposure to tobacco smoke, dust, and chemicals.^[2]

Alpha-1 antitrypsin deficiency (AATD) may first be suspected in people with evidence of liver disease at any age, or lung disease (such as emphysema), especially when there is no obvious cause or it is diagnosed at a younger age.

Confirming the diagnosis involves a blood test showing a low serum concentration of the alpha-1 antitrypsin (AAT) protein, and either:

• detecting a functionally deficient AAT protein variant by isoelectric focusing (a method for detecting mutations); or
• detecting SERPINA1 gene mutations on both copies of the gene with molecular genetic testing. (This confirms the diagnosis when the above-mentioned tests are not performed or their results are not in agreement.)^[3]

Specialists involved in the diagnosis may include primary care doctors, pulmonologists (lung specialists), and/or hepatologists (liver specialists).^[4]

Treatment of alpha-1 antitrypsin deficiency (AATD) depends on the symptoms and severity in each person. COPD and other related lung diseases are typically treated with standard therapy.^[3][4] Bronchodilators and inhaled steroids can help open the airways and make breathing easier.^[4]

Intravenous augmentation therapy (regular infusion of purified, human AAT to increase AAT concentrations) has been recommended for people with established fixed airflow obstruction (determined by a specific lung function test).^[3] This therapy raises the level of the AAT protein in the blood and lungs.^[4]

Lung transplantation may be an appropriate option for people with end-stage lung disease. Liver transplantation is the definitive treatment for advanced liver disease.^[3]

When present, panniculitis may resolve on its own or after dapsone or doxycycline therapy. When this therapy does not help, it has responded to intravenous augmentation therapy in higher than usual doses.^[3]

All people with severe AATD should have pulmonary function tests every 6 to 12 months. Those with ATT serum concentrations 10% to 20% of normal should have periodic evaluation of liver function to detect liver disease. People with established liver disease should have periodic ultrasounds of the liver to monitor for fibrotic changes and liver cancer (hepatocellular carcinoma).^[3]

Yearly vaccinations against influenza and pneumococcus are recommended to lessen the progression of lung disease. Vaccination against hepatitis A and B is recommended to lessen the risk of liver disease. People with AATD should avoid smoking and occupations with exposure to environmental pollutants.^[3]

Parents, older and younger siblings, and children of a person with severe AATD should be evaluated to identify as early as possible those who would benefit from treatment and preventive measures.^[3]