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About alpha1-antitrypsin (AAT) deficiency

AAT deficiency, sometimes known simply as “alpha-1”, is a genetic disease primarily affecting the lungs and liver. It is characterised by a decrease in circulating levels of a protein called alpha1 antitrypsin.1 

AAT deficiency is the major known genetic risk factor for chronic obstructive pulmonary disease (COPD), particularly emphysema with basilar predominance.2 COPD is characterised by respiratory symptoms that are persistent with limitation of airflow due to airway or alveoli dysfunction.3

Respiratory symptoms of AAT deficiency are often indistinguishable from smoking-induced COPD or asthma, chronic bronchitis and emphysema (usually in combination), including:4,5

  • Wheezing
  • Cough
  • Excess sputum production
  • Severe dyspnoea on exertion

Risks associated with AAT deficiency:

  • Chronic obstructive pulmonary disease (COPD)1,6
  • Reduced life expectancy1,6
  • Cirrhosis in infants, children and adults with specific genetic variants1,6
  • Necrotising panniculitis, a rare skin disease1,6
  • Wegener's disease (vasculitis)1,6

There are no clinical characteristics that rule out the diagnosis of AAT deficiency, nor predictive clinical, demographic or age-related characteristics that  predict a diagnosis of AAT deficiency.7 Because AAT deficiency cannot be diagnosed on clinical presentation alone, it is underdiagnosed and should be confirmed with laboratory testing.6,8-10

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The longer AAT deficiency remains undiagnosed, the greater the risk of irreparable lung damage10,11

What is - What is

What is alpha1 antitrypsin (AAT)?

AAT (the protein) is a protease inhibitor (Pi), an enzyme, that is produced mainly in the liver. AAT is continuously produced and transported in the bloodstream and can be found at high concentration in the lungs (Figure 1).12 During episodes of inflammation, infection, cancer or during pregnancy, AAT production is increased, so it is known as an acute phase protein.13

Why is AAT critical to protect the lungs?

The most important function of alpha1 antitrypsin is the inactivation of proteolytic enzymes in the lung (Figure 2). Such enzymes are released during an immune response, which is frequent since the lungs are continuously exposed to airborne pathogens. While these proteolytic enzymes are key for destroying pathogens, if uncontrolled, they have the potential to destroy lung tissue.12

When there is a deficiency of AAT (Figure 3) the excess of these proteolytic enzymes, particularly neutrophil elastase, the lung matrix components, alveolar structures and blood vessels are gradually destroyed. This manifests as chronic obstructive bronchitis or emphysema.12  

AAT is critical to protect the lungs12

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What causes liver disease in AAT deficiency?

Certain genetic variants are also associated with liver disease. For example, the PiZ variant is thought to cause the AAT protein to form large polymers that accumulate in the liver cells, causing cellular injury and cell death.12

think what AAT

AAT: alpha1 antitrypsin; COPD: chronic obstructive pulmonary disease.

What is references


  1. Stoller JK, Lacbawan FL, Aboussouan LS. Alpha-1 antitrypsin deficiency. In: Pagon RA, Adam MP, Ardinger HH, et al. editors. GeneReviews(R). Seattle (WA)2006 (updated 2014).
  2. World Health Organization. Alpha 1-antitrypsin deficiency: memorandum from a WHO meeting. Bull World Health Organ. 1997;75(5):397-415.
  3. Global Initiative for Chronic Obstructive Lung Disease. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. 2020 [Updated]. Available at: http://goldcopd.org/gold-2017-global-strategy-diagnosis-management-prevention-copd/.
  4. Rachelefsky G, Hogarth DK. Issues in the diagnosis of alpha 1-antitrypsin deficiency. J Allergy Clin Immunol. 2008;121(4):833-8.
  5. Strange C, Stoller JK, Sandhaus RA, et al. Results of a survey of patients with alpha-1 antitrypsin deficiency. Respiration. 2006;73(2):185-90.
  6. ATS, ERS. American Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency. Am J Respir Crit Care Med. 2003;168(7):818-900.
  7. Sandhaus RA, Turino G, Brantly ML, et al. The diagnosis and management of alpha-1 antitrypsin deficiency in the adult (Clinical Practice Guidelines). Chronic Obstr Pulm Dis (Miami). 2016;3(3):668-82.
  8. Stockley JA, Ismail AM, Hughes SM, et al. Maximal mid-expiratory flow detects early lung disease in a1-antitrypsin deficiency. Eur Respir J. 2017;49(3).
  9. Miravitlles M, Dirksen A, Ferrarotti I, et al. European Respiratory Society statement: diagnosis and treatment of pulmonary disease in α1-antitrypsin deficiency. European Respiratory Journal. 2017;50(5).
  10. Campos MA, Wanner A, Zhang G, et al. Trends in the diagnosis of symptomatic patients with alpha1-antitrypsin deficiency between 1968 and 2003. Chest. 2005;128(3):1179-86.
  11. Vidal R, Blanco I, Casas F, et al. Guidelines for the diagnosis and management of alpha1-antitrypsin deficiency. Arch Bronconeumol. 2006;42(12):645-59.
  12. Köhnlein T, Welte T. Alpha-1 antitrypsin deficiency: pathogenesis, clinical presentation, diagnosis, and treatment. Am J Med. 2008;121(1):3-9.
  13. Bals R, Kohnlein T. Alpha-1 Antitrypsin Deficiency. Pathophysiology, Diagnosis, and Treatment. 2009.