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Diseases

Genetic and Rare Diseases Information Center (GARD)

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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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Inheritance


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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.[1] 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.[2] The S allele produces moderately low levels of protein, and the Z allele produces very little protein.[1]

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.[1] 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.[2] 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.[2] 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.[1] Individuals with an MS or SS combination usually produce enough alpha-1 antitrypsin to protect the lungs.[2]

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.[3] 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

References
  1. Alpha-1-Antitrypsin Deficiency. NORD. December 31, 2010; http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Alpha-1-Antitrypsin%20Deficiency. Accessed 4/16/2011.
  2. Alpha-1 antitrypsin deficiency. Genetics Home Reference. August 2009; http://ghr.nlm.nih.gov/condition/alpha-1-antitrypsin-deficiency. Accessed 6/28/2011.
  3. Kamilla Schlade-Bartusiak, Diane W Cox. Alpha1-Antitrypsin Deficiency. GeneReviews. February 6, 2008; http://www.ncbi.nlm.nih.gov/books/NBK1519/. Accessed 4/16/2011.