underdiagnosed list

Alpha1-antitrypsin (AAT) deficiency is underdiagnosed

Based on a survey of 58 countries, it is estimated that worldwide there are:

  • 116 million carriers (PiMS and PiMZ alleles)1
  • 3.4 million individuals with severe deficiency (PiS and PiZ allele combinations)1

In the United States:

  • Over 90% of people with AAT deficiency are believed to be undiagnosed2,3
  • Up to 3% of all chronic obstructive pulmonary disease (COPD) cases may be due to an underlying AAT deficiency2

underdiagnosed picture

Alpha1-antitrypsin (AAT) deficiency in comparison to other rare pulmonary diseases3

underdiagnosed list 2

AAT deficiency may be underdiagnosed because respiratory symptoms of AAT deficiency are indistinguishable from smoking-induced COPD or asthma, chronic bronchitis and emphysema (usually in combination)4,5, including: 

  • Wheezing4,5
  • Cough4,5
  • Excess sputum production4,5
  • Severe dyspnoea on exertion4,5

underdiagnosed callout

Smoking history may confound the proper diagnosis of AAT deficiency: many AAT-deficient patients are either current or ex-smokers6,7

underdiagnosed Because

Because no clinical characteristics rule out the diagnosis of AAT deficiency, and no demographic or age-related characteristics can predict AAT deficiency, it is underdiagnosed and should be confirmed with laboratory testing.2,8-11

Once diagnosed, patients can be counselled to adopt healthier lifestyles, particularly with regards to smoking and other preventative measures.2

Since AAT deficiency is a genetic disease, early detection may also help a patient’s relatives regardless of whether or not they are symptomatic.2

underdiagnosed button

think what AAT

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

underdiagnosed references


  1. de Serres FJ. Worldwide racial and ethnic distribution of alpha1-antitrypsin deficiency: summary of an analysis of published genetic epidemiologic surveys. Chest. 2002;122(5):1818-29.
  2. 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.
  3. Orphanet Report Series. Prevalence and incidence of rare diseases: January 2019 - Number 1. 2019 [Updated]. Available at: http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf
  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. DeMeo DL, Sandhaus RA, Barker AF, et al. Determinants of airflow obstruction in severe alpha-1-antitrypsin deficiency. Thorax. 2007;62(9):806-13.
  7. The Alpha-1-Antitrypsin Deficiency Registry Study Group. Survival and FEV1 decline in individuals with severe deficiency of alpha1-antitrypsin. Am J Respir Crit Care Med. 1998;158(1):49-59.
  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. 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.
  11. 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.