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Alpha-1 antitrypsin deficiency



AATD is an inherited disorder caused by mutations in the SERPINA1 gene, leading to a deficiency or dysfunction of the α-1 antitrypsin protein.
The pathophysiology of α-1 antitrypsin deficiency involves a deficiency in the α-1 antitrypsin protein. The imbalance of proteases and antiproteases leads to unopposed neutrophil elastase activity and subsequent tissue damage in the lungs.
The prevalence of α-1 antitrypsin deficiency in Europe is estimated at 20 per 100,000 population.
Disease course
Clinically, patients with α-1 antitrypsin deficiency often present with symptoms such as dyspnea, chronic cough, and recurrent respiratory infections. In some cases, the disease may also manifest as unexplained bronchiectasis. In rare cases, it can also lead to liver disease, including chronic hepatitis, cirrhosis, and HCC.
Prognosis and risk of recurrence
The prognosis can vary widely among patients. The disease is generally progressive, with the potential for significant lung damage over time.


Key sources

The following summarized guidelines for the evaluation and management of alpha-1 antitrypsin deficiency are prepared by our editorial team based on guidelines from the Global Initiative for Chronic Obstructive Lung Disease (GOLD 2022), the National Comprehensive Cancer Network (NCCN 2022), the European Respiratory Society (ERS 2017), the Alpha-1 Foundation (Alpha-1 2016), the American Association for the Study of Liver Diseases ...
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Screening and diagnosis

Clinical presentation
As per ERS 2017 guidelines:
Recognize that lung disease in α-1 antitrypsin deficiency generally presents at a younger age than usual COPD and may be misdiagnosed as asthma.
Recognize that patients with α-1 antitrypsin deficiency are more likely to have basal emphysema than patients with usual COPD.
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  • Screening of family relatives

  • Indications for testing (lung disease)

  • Indications for testing (liver disease)

  • Indications for testing (vasculitis)

  • Indications for testing (panniculitis)

Diagnostic investigations

AAT levels: as per ERS 2017 guidelines, obtain quantitative measurement of α-1 antitrypsin levels in the blood to identify α-1 antitrypsin deficiency.

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  • Protein electrophoresis

  • Genetic testing

  • Pulmonary function testing

  • Chest imaging

Medical management

Setting of care: as per ERS 2017 guidelines, manage patients with α-1 antitrypsin deficiency in supervision by reference centers of excellence at a national or regional level.

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  • Augmentation therapy

Nonpharmacologic interventions

Smoking cessation: as per Alpha-1 2016 guidelines, advise smoking cessation and avoidance of exposure to tobacco in patients with α-1 antitrypsin deficiency.

Surgical interventions

Lung volume reduction surgery: as per ERS 2017 guidelines, consider performing surgical volume reduction and endobronchial valve placement in selected patients with α-1 antitrypsin deficiency, with a careful appraisal of risks and benefits assessed by a multidisciplinary team experienced in lung volume reduction and α-1 antitrypsin deficiency.

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  • Lung transplantation

  • Liver transplantation

Follow-up and surveillance

Surveillance for lung disease: as per ERS 2017 guidelines, obtain annual pulmonary function testing including post-bronchodilator FEV1 and gas transfer to monitor for disease progression.
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  • Surveillance for liver disease

  • Surveillance for HCC