Alpha-1 Antitrypsin Deficiency

What is Alpha-1 Antitrypsin Deficiency?

Alpha-1 antitrypsin (AAT) is an important protein produced by the liver, which is released into the bloodstream and travels to the lungs. It protects the lungs from the destructive actions of common illnesses and exposures, particularly tobacco smoke.

Alpha-1 antitrypsin deficiency (Alpha-1) is a genetic (inherited) disorder which results in an absence or low levels of AAT protein in the blood. These low levels prevent AAT protecting the lungs from the destructive damage of neutrophil elastase resulting in lung tissue damage. Alpha-1 is not a rare disease but it is massively under-diagnosed. It classically presents with early-onset emphysema and liver disease in childhood and occasionally in adulthood. Both the ATS/ERS and WHO recommend Alpha-1 testing for the following patients:

  • All COPD patients
  • All non-responsive asthmatics (adults/adolescents)
  • All patients with cryptogenic cirrhosis/liver disease
  • All first degree relatives of patients and carriers with AAT deficiency

The National Alpha-1 Targeted Detection Programme was established in 2004 to provide testing free of charge to suspected individuals throughout Ireland.

What causes Alpha-1 Antitrypsin Deficiency?

AATD occurs due to mutations in the SERPINA1 gene located on chromosome 14. There are over 100 mutations with S and Z the most common and they account for 95% of Alpha-1 cases. These mutations confer varying risks of lung and/or liver disease. Alpha-1 is the only proven genetic risk factor for COPD. A person who inherits one normal gene (M) and one variant Alpha-1 gene is known as a carrier. The MZ and MS genotypes are the most common carrier types and it is unclear whether they are at increased risk of disease.

Incidence of Alpha-1 in Ireland

Ireland has one of the highest incidences in the world. Over 2,000 Irish individuals have severe Alpha-1 (ZZ) and over 200,000 are carriers (MZ). A further 10,000 Irish individuals are at risk of developing lung and liver disease from having the SZ genotype.

Treatment of Alpha-1 Antitrypsin Deficiency

At present, there is no specific cure for patients with Alpha-1. The treatment focus for Alpha-1 patients is to prevent further loss of lung function. With this in mind all Alpha-1 patients are advised to:

  • Stop smoking immediately as smoking destroys the small levels of AAT protein that are present in these patients.
  • Get the annual flu vaccine along with the pneumococcal vaccine every 5 years.
  • Treat lung infections aggressively with antibiotics to prevent further lung destruction.

Augmentation therapy trials are currently ongoing in Ireland. This involves receiving AAT protein which has been purified from the blood of human donors with normal alpha-1 genes. This increases the level of AAT in the blood which may help slow the loss of lung function.

Alpha-1 symptoms are similar to asthma and COPD symptoms and patients receive similar therapies:

  • Bronchodilators
  • Corticosteriods
  • Supplementary Oxygen
  • Lung (and Liver) Transplantation

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