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Alpha 1 Antitrypsin Deficiency (AATD) DRAFT

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Alpha 1 Antitrypsin Deficiency (AATD) is an autosomal recessive disorder affecting about 1:2500 people. In AATD there is an increased risk of development of emphysema at an earlier age than usual, for example, in the third to fourth decades of life. Less frequently, liver disease may arise and cause cirrhosis and liver failure in children or adults. Environmental factors, particularly cigarette smoking, increase the risk of emphysema at an earlier age and high alcohol use increases risk of liver damage.

Most carriers for AATD are unaffected, but their risk of emphysema is also exacerbated by smoking.

Most individuals with AATD can be managed in primary care with lifestyle advice, but referral to a specialist service (Respiratory, Hepatology or Paediatrics) may be required if there are significant symptoms.

The SERPINA1 gene produces Alpha-1 Antitrypsin (AAT), a protein that protects airways from proteolytic damage. The different copies (forms) of a gene are called alleles. Every individual has two SERPINA1 alleles and inherits one from each parent. The three main alleles to be aware of in AAT are M, S and Z. M is the most common and associated with normal AAT levels. Z and S are alleles associated with lower AAT levels. S causes moderately reduced but sufficient AAT levels, whereas Z causes very low AAT levels which are associated with deficiency. Individuals with one M allele and another abnormal allele (S or Z) are called ‘carriers’. Other rarer alleles also exist. 

Testing and who to refer


Who to test for AATD in primary care:

  • As part of non- invasive liver screen of patients with persistently deranged liver function tests.
  • Consider testing in early-onset emphysema or emphysema in the absence of any risk factors (e.g. smoking and occupational dust exposure).
  • Consider testing if there is a strong family history of lung or liver disease.
  • Consider testing first degree relatives or partners of those who are affected or confirmed carriers of AATD.
  • Test and consider referral to clinical genetics:
    • Members of a couple of reproductive age who have abnormal alleles (e.g. MZ, MS, ZS, ZZ or other rare alleles), as they may be at risk of having a child with alpha-1-antitrypsin deficiency.
    • Parents of reproductive age who have a child who has been diagnosed with alpha-1-antitrypsin deficiency.

Practicalities about testing

Also see regional pathway document.

  • For symptoms request AAT serum levels only
  • For relatives/partners of those who are affected or confirmed carriers of AATD, it is recommended to test both serum alpha-1 antitrypsin (AAT) levels and AATD phenotype (ordered through ICE). Measurement of serum AAT level alone is not reliable for determining carrier status. This is because the range of serum AAT levels among most carriers may overlap with the normal serum range and/or may be elevated in certain situations eg during periods of acute inflammation and in pregnancy.

More detailed genomic testing (DNA analysis) is rarely indicated, but in certain situations, genetic testing may be recommended following the initial AAT testing (above) to clarify a patient’s status. This can be organised in primary care.

Bristol ICE request for AATD:

  •  Alpha 1 antitrypsin phenotype | North Bristol NHS Trust (
  • Enter 'alpha’ into the search bar on the left hand side
  • Select ‘alpha-1-antitrypsin’ option on the right to order alpha-1-antitrypsin’ serum levels
  • Also select ‘alpha -1-AT phenotype'.
  • This will open a window asking if the patient is known to clinical genetics. Select 'no' or ‘yes’ as appropriate.
  • You will then be prompted to enter the relative and phenotype details of the patient. Do this, then click 'OK‘. If relevant relative not specified, just pick any.
  • Then click ‘Continue with request…’

Patient Information Leaflet




Phenotype (Pi)

Individuals risk of AATD




Family Recommendations


No risk

Reassurance, routine lifestyle advice.

None required.



No risk

Reassurance, lifestyle advice regarding smoking and alcohol.

Provide Patient / Family Information Leaflet






Slight risk

  • Lifestyle advice regarding smoking and alcohol.
  • Refer to relevant specialist* if symptoms.
  • FDRs can seek advice from own GP for phenotype and levels testing.


  • If planning pregnancy, phenotype partner.


  • If partner also has abnormal allele(s) refer to Clinical Genetics Service for genetic counselling.


Increased risk


  • Refer to relevant specialist*.
  • Lifestyle advice regarding smoking and alcohol, including smoking cessation referral.


Significant risk

Any phenotype where AAT level is undetectable**

Significant risk

Other reported phenotypes including rare alleles.


 Will vary depending on type of alleles. Specialist advice can be sort.

* Relevant specialist = Respiratory, Hepatology or Paediatrics.

** If a patient has low levels of AAT and may have other rare alleles, genetic testing of the SERPIN1A gene can be considered based on criteria in the National Genomic Test Directory test R191 (rare- and-inherited-disease-eligibility-criteria-v2.pdf (


The Clinical Genetics Department is based at St Michaels Hospital and offers genetic assessment, investigations, diagnosis and counselling

Referrals should be made via the Clinical Genetics Referral Assessment Service (RAS) on eRS.

Refer to Respiratory, Hepatology or Paediatrics via eRS as appropriate.


Further sources of information on Alpha-1-Antitrypsin deficiency can be found at:


Questions regarding this pathway can be directed to the Bristol Clinical Genetics Service ubh-

Efforts are made to ensure the accuracy and agreement of these guidelines, including any content uploaded, referred to or linked to from the system. However, BNSSG ICB cannot guarantee this. This guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer, in accordance with the mental capacity act, and informed by the summary of product characteristics of any drugs they are considering. Practitioners are required to perform their duties in accordance with the law and their regulators and nothing in this guidance should be interpreted in a way that would be inconsistent with compliance with those duties.

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