Alpha-1 Antitrypsin Deficiency – A Genetic Risk Factor for COPD

Alpha-1 antitrypsin deficiency (AATD) is a hereditary disorder characterised by low circulating levels of the key antiprotease alpha-1 antitrypsin (AAT) and is associated with the development of chronic obstructive pulmonary disease (COPD), often by the 3rd or 4th decade, and liver disease. The two most common SERPINA1 mutations associated with AATD are the Z and S mutations, and the vast majority of AATD individuals diagnosed with COPD are ZZ homozygotes. AATD is an under-diagnosed condition with the majority of cases misdiagnosed as COPD. The World Health Organisation (WHO) and the American Thoracic Society/European Respiratory Society (ATS/ERS) advocate a targeted screening approach for the detection of AATD in patients with COPD, non-responsive asthma, cryptogenic liver disease and first degree relatives of known AATD patients (Alpha 1antitrypsin deficiency: memorandum from a WHO meeting 1997; American Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency. 2003). It is our contention that a diagnosis of AATD gives the clinician a vital and unique opportunity for early medical intervention and the possible prevention of COPD in both the affected individual and first-degree relatives. Unfortunately, despite huge strides in awareness and understanding of this condition, this opportunity is too often missed.