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Alpha-1 Antitrypsin Deficiency P002

Document
Last amended 
11 February 2021
Current RMA Instruments
Reasonable Hypothesis SOP
29 of 2015
Balance of Probabilities SOP 
30 of 2015
Changes from previous Instruments

SOP Bulletin 179

ICD Coding
  • ICD-9-CM Codes: 277.6
  • ICD-10-AM Codes: E88.0
Brief description

Alpha-1 antitrypsin deficiency is an autosomal co-dominant genetic disorder of plasma protein metabolism.  It results in reduced serum levels of alpha-1 antitrypsin (AAT), a protease inhibitor.  Common clinical manifestations include emphysema and cirrhosis of the liver.

Confirming the diagnosis

The diagnosis is generally made based on blood (serum) testing for the AAT level, together with genetic testing.  Such testing is usually indicated by unexplained/early onset emphysema, unexplained chronic liver disease, or a family history.  Relevant imaging and function testing of the lungs and liver are also likely to be performed.

The relevant medical specialist is a respiratory physician,hepatolgist/gastroenterologist, or geneticist.

Additional diagnoses covered by SOP
  • Chronic liver disease due to alpha-1 antitrypsin deficiency*
  • Emphysema due to alpha-1 antitrypsin deficiency*

* The SOP for COPD does not have an AAT defciency factor, whereas the SOP for cirrhosis does - and so cirrhosis due to AAT deficiency is covered by both SOPs.

Clinical onset

The genetic abnormality is present from birth.  The condition is typically asymptomatic early in life (and may remain so).  It may not come to attention and be diagnosed until clinical manifestations develop which is likely to be in middle age (and earlier in smokers).  

Clinical worsening

The only SOP worsening factor is for inability to obtain appropriate clinical management.  Natural progression of the disease varies with the phenotype.  Worsening beyond the normal progression of the disease needs to be evident before a clinical worsening factor can be considered.  Augmentation therapy is available which can modify the course of (particularly lung) disease in AAT deficiency.  Apart from this specific therapy, treatment is supportive and protective of the liver and the lungs.

Current understanding of the natural history of Alpha-1 antitrypsin deficiency is patchy, with some aspects being reasonably clear and others still murky.  Within the first two decades of life, liver dysfunction is the major threat to the health of affected individuals, and pulmonary dysfunction is not a major concern. Beyond the first two to three decades of life, the natural history of individuals with severe deficiency of AAT is less clear.  The prevalence of COPD among subjects with severe AAT deficiency has been estimated to be 75 to 85 percent, with liver disease occurring in 12 to 16 percent.