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Alpha 1-antitrypsin deficiency

Other Names for this Disease
  • A1AT deficiency
  • AAT deficiency
  • AATD
  • Alpha 1 antitrypsin deficiency
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What is alpha 1-antitrypsin deficiency?

What causes alpha 1-antitrypsin deficiency?

How is alpha 1-antitrypsin deficiency inherited?

How is alpha-1-antitrypsin deficiency diagnosed?

What is alpha 1-antitrypsin deficiency?

Alpha 1-antitrypsin deficiency is an inherited disorder that can cause lung disease in adults and liver disease in adults and children.[1] Alpha-1 antitrypsin (AAT) is a protein that protects the lungs. The liver usually makes the protein, and releases it into the bloodstream.[2] Because of a mutation in the SERPINA1 gene, some people have little or no AAT.[1][2] Not having enough AAT may lead to emphysema or liver problems. Smoking increases the risk. A deficiency of AAT can be treated but not cured. One treatment involves adding to or replacing the missing protein. More severe cases may require a lung transplant.[2] This condition is caused by mutations in the SERPINA1 gene and inherited in an autosomal co-dominant fashion.[1]
Last updated: 7/26/2011

What causes alpha 1-antitrypsin deficiency?

Mutations in the SERPINA1 gene cause alpha-1 antitrypsin deficiency. This gene provides instructions for making a protein called alpha-1 antitrypsin, which protects the body from a powerful enzyme called neutrophil elastase. Neutrophil elastase is released from white blood cells to fight infection, but it can attack normal tissues (especially the lungs) if not tightly controlled by alpha-1 antitrypsin.[1]

Mutations in the SERPINA1 gene can lead to a shortage (deficiency) of alpha-1 antitrypsin or an abnormal form of the protein that cannot control neutrophil elastase. Without enough functional alpha-1 antitrypsin, neutrophil elastase destroys alveoli and causes lung disease. Abnormal alpha-1 antitrypsin can also accumulate in the liver and damage this organ.[1]
Last updated: 7/26/2011

How is alpha 1-antitrypsin deficiency inherited?

Alpha 1-antitrypsin deficiency (A1AD) is caused by mutations (changes) in the SERPINA1 gene, which is responsible for production of the alpha-1 antitrypsin protein. Over 100 different mutations in the SERPINA1 gene have been identified, but the most common are termed S and Z, whereas the normal version (allele) of the gene is termed M.[3] The M allele produces normal levels of alpha-1 antitrypsin. Most people in the general population have two copies of the M allele (MM) in each cell.[4] The S allele produces moderately low levels of protein, and the Z allele produces very little protein.[3]

A1AD is inherited as an autosomal recessive genetic condition. Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent.[3] Each parent who has one abnormal copy of the gene is referred to as a carrier; carriers typically do not show signs and symptoms of a recessively inherited condition. When two carrier parents have a child, with each pregnancy there is a 25% (1 in 4) risk that the child will have the condition, a 50% (1 in 2) risk for the child to be a carrier like each of the parents, and a 25% chance for the child to not be a carrier and not have the condition (and therefore not pass the abnormal gene on to future generations). Furthermore, when an individual is a carrier for a recessive condition, each successive generation has about half of the risk to be a carrier as the person before.

People who have two copies of the Z allele (ZZ), and therefore have extremely low levels the alpha 1-antitrypsin protein, are likely to have A1AD.[4] If an individual receives one normal allele and one Z allele (MZ), they do have a slightly increased risk for impaired lung or liver function.[4] If an individual receives one S allele and one Z allele (SZ) they have an increased risk to develop chronic obstructive pulmonary disease, particularly if they smoke.[3] Individuals with an MS or SS combination usually produce enough alpha-1 antitrypsin to protect the lungs.[4]

If an individual has a relative who has been diagnosed with A1AD, carrier testing is available for the affected individual's siblings and children; this is typically done by PI typing (isoelectric focusing) or mutation analysis.[5] Individuals who are concerned about their personal risk to inherit A1AD or carry a mutation for the condition should speak with a genetics professional.
Last updated: 6/28/2011

How is alpha-1-antitrypsin deficiency diagnosed?

Alpha1-antitrypsin deficiency is suspected in people with evidence of lung disease (i.e., emphysema, asthma, persistent airflow obstruction, and/or chronic bronchitis) and/or evidence of liver disease at any age. The diagnosis of Alpha1-antitrypsin deficiency relies on the demonstration of low plasma concentration of alpha1-antitrypsin and observation of a deficient variant of the protein AAT by protease inhibitor (PI) typing OR detection by molecular genetic testing of mutations in both copies of SERPINA1, the gene encoding AAT.[6]

For a comprehensive review of Alpha1-antitrypsin deficiency including its diagnosis, you can visit GeneReviews at the following link. GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.

You can also learn more about Alpha1-antitrypsin testing on the Lab Tests Online Web site. A public resource developed by the American Association for Clinical Chemistry.

Last updated: 7/26/2011

  1. Alpha 1-antitrypsin deficiency. Genetics Home Reference (GHR). August 2009; Accessed 7/26/2011.
  2. Alpha 1-Antitrypsin Deficiency. MedlinePlus. January 2011; Accessed 7/26/2011.
  3. Alpha-1-Antitrypsin Deficiency. NORD. December 31, 2010; Accessed 4/16/2011.
  4. Alpha-1 antitrypsin deficiency. Genetics Home Reference. August 2009; Accessed 6/28/2011.
  5. Kamilla Schlade-Bartusiak, Diane W Cox. Alpha1-Antitrypsin Deficiency. GeneReviews. February 6, 2008; Accessed 4/16/2011.
  6. Schlade-Bartusiak K, Cox DW. Alpha1-Antitrypsin Deficiency . GeneReviews. February 2008; Accessed 7/26/2011.