Alpha1-antitrypsin (A1AT) deficiency is an inherited disorder that may lead to lung and/or liver disease.
A1AT is a protein made by cells in the liver and passed into the bloodstream. Its job is to protect organs including the lungs from damage by other proteins called protease enzymes. In A1AT deficiency, the levels of A1AT are reduced, or the A1AT produced is abnormal. A1AT protects the body against an enzyme designed to attack infections but which can damage normal tissues if let loose. A1AT deficiency mainly affects the lungs and liver. Lung disease can be serious and made worse by environmental factors such as smoking and pollution.
About one in every 2500 people in Australia inherit mutations in the SERPINA1 gene that results in A1AT deficiency. It is most common among people of Northern European or Iberian (Spanish peninsula) descent. It is thought that a significant number of people are unaware that they have the disorder.
Causes of alpha1-antitrypsin deficiency
A1AT is an inherited condition caused by an abnormality of the SERPINA1 gene.
Not everyone who inherits an abnormal gene will develop disease. Whether a person develops symptoms or not will depend upon the alleles (variations of the gene) they have inherited and the levels of A1AT in their blood. It is usually only when the A1AT levels are less than 30 per cent of normal that lung disease develops. Smoking greatly increases the risk of developing lung disease in people with A1AT deficiency.
Symptoms of alpha1-antitrypsin deficiency
The symptoms of A1AT deficiency most often appear between the ages of 20 and 50. Lung symptoms include shortness of breath on exercise, wheezing, cough, lung infections, tiredness and weight loss. Emphysema coming on early in adult life could be due to A1AT deficiency. Fifteen per cent of adults with the condition and 10 per cent of children develop liver disease causing jaundice (yellowing of skin and eyes), a swollen abdomen and an increased risk of liver cancer.
Tests for alpha1-antitrypsin deficiency
A1AT deficiency is diagnosed by testing the levels of A1AT in the blood, and there are also genetic tests available. Other tests your doctor may request include liver function tests, lung function tests, imaging of the lungs and/or liver, and genetic testing. Anyone with unexplained liver disease, chronic obstructive pulmonary disease (COPD), or a condition called bronchiectasis (cough with sputum and seriously damaged lungs) should be tested. It is important to be referred for genetic counselling so that appropriate testing of family members can be performed.
Treatment for alpha1-antitrypsin deficiency
Medical care of people with A1AT deficiency and lung disease includes treatment for emphysema, such as bronchodilators and other medicines to help with breathlessness, immunisations for influenza, hepatitis and pneumococcal infections and prompt treatment of chest infections. The most important thing people with A1AT deficiency can do to help themselves is to stop smoking and be on an exercise programme.
There is a specific therapy for emphysema due to A1AT deficiency which is called A1AT augmentation, or replacement therapy and it’s given by intravenous infusion. It is available in Australia but not subsidised. Augmentation therapy probably only helps a subset of people with the condition and the real benefits are still unclear.
In severe cases of lung or liver disease with A1AT deficiency, liver and lung transplantation may be considered.
