Alpha-1 antitrypsin deficiency is a genetic condition that can predispose an individual to lung and liver diseases, including cirrhosis of the liver and emphysema.

Alpha-1 antitrypsin deficiency is caused by pathogenic variants in the SERPINA1 gene. Variants in this gene lead to a shortage or deficiency of alpha-1 antitrypsin, which is important for protecting normal tissues, especially the lungs, from damage.

GeNotes has produced a helpful summary about the condition:Alpha-1 antitrypsin deficiency — Knowledge Hub

Around 1 in 25 people in the white British population are carriers of alpha-1 antitrypsin deficiency. The carrier frequency varies amongst different populations.

Patients can be offered genetic testing if they meet the eligibility criteria outlined in the National Genomic Test Directory. To view these criteria, visit our ‘Order a Test’ page: Order testing for A1AT

Funding for genetic investigations is now held by the laboratory hub. Primary care physicians are able to request certain genetic investigations directly and will not be charged.

Before arranging testing, you should explain the possible outcomes of the test to your patient. You can use the Record of Discussion form to help with this

You also need to complete a Test Request Form

The Record of Discussion form and Test Order form can be downloaded from our ‘Order a Test’ page: Order testing for A1AT

The blood sample should be stored in an EDTA tube (purple top) and sent with the Test Request Form to

Genetics Laboratory
5th Floor Tower Wing
Guy’s Hospital
London
SE1 9RT

The Test Order form can be downloaded from our ‘Order a Test’ page: Order testing for A1AT

The Record of Discussion form can be used to explain to the patient what the potential outcomes of the test could be.

The Record of Discussion form can be downloaded from our ‘Order a Test’ page: Order testing for A1AT

The sample should be collected in an EDTA tube (purple top)

Please include as much detail as possible in this box, including the reason for offering the patient a test.

If the patient is having testing because their relative has been found to have a causative gene variant, please include details of the affected relative (name and DoB) and your patient’s relationship to the relative e.g. brother.

The code for alpha-1-antitrypsin deficiency testing is ‘R191 Alpha-1-antitrypsin deficiency’. Please write this on the test request form.

Please write your name and contact details in this box. As the requesting clinician, you will receive the report and it is your responsibility to inform the patient of the result.

The laboratory can only email genetic test results to the email address you provide on the form. It may be helpful to use a ‘group’ or departmental email address to reduce the chances of a result email being missed.

Alpha-1 antitrypsin deficiency is inherited in an autosomal recessive fashion, which means that affected individuals have two altered copies of the SERPINA1 gene.

There are several different forms (alleles) of the SERPINA1 gene:

• The normal allele (called M) produces normal levels of alpha-1 antitrypsin.

Other alleles lead to reduced levels of Alpha-1 antitrypsin.  For example:

• The S allele produces moderately low levels of the protein
• The Z allele produces significantly low levels of protein.

Carriers of alpha-1 antitrypsin deficiency have one normal copy of the  gene and one altered copy of the gene and are known as MZ or MS carriers. Carriers are generally well and healthy and do not develop the problems associated with the condition. It is important however for carriers to ensure that they do not smoke.

Individuals who are affected with alpha-1 antitrypsin deficiency have the ZZ type.

Those with ZS have an increased risk of developing lung disease, particularly if they smoke.

There is no need to refer your patient to Clinical Genetics. Because so many people are carriers of alpha-1 antitrypsin deficiency, Clinical Genetics do not usually see these patients.

If a couple are both carriers of the MZ phenotype, there is a risk of them having a child with the ZZ type of the condition. They can be referred to Clinical Genetics to discuss their reproductive options/or the implications for their children.

If your patient has a partner, we would recommend that they have carrier testing for the condition which can be done through their GP. This testing can be carried out through the local pathology laboratory by requesting ‘phenotyping’ and testing for levels of alpha-1 antitrypsin.

If a couple are both carriers of the MZ phenotype, there is a risk of them having a child with the ZZ type of the condition. They can be referred to Clinical Genetics to discuss their reproductive options/or the implications for their children.

GeNotes have produced a helpful summary about alpha-1-antitrypsin deficiency Access GeNotes

If you cannot find the answer to your question on this page, you can contact your local Clinical Genetics service for support.

• Clinical Genetics at Guy’s and St Thomas’s NHS Foundation Trust: geneticscorrespondence@nhs.net
• Clinical Genetics at St George’s University Hospitals NHS Foundation Trust: secretaries@stgeorges.nhs.uk

The pages below have been developed to support people affected by  alpha-1-antitrypsin deficiency:

• Alpha-1 Antitrypsin Deficiency Support
• Asthma + Lung UK: Alpha-1-antitrypsin deficiency