Alpha-1-antitrypsin deficiency

Inheritance

How does alpha-1 antitrypsin deficiency run in families?

Everyone has two copies of the gene associated with alpha-1 antitrypsin deficiency (AATD), which is called SERPINA1. We inherit our genes from our parents and pass them to our children. A person can inherit alpha-1 antitrypsin deficiency (AATD) if both of their parents carry a change, or mutation, in the SERPINA1 gene. Their parents, called AATD carriers, may not have symptoms of AATD themselves.

Carriers have one SERPINA1 gene with a mutation and one copy without it. If two AATD carriers have children together, they have a 25% (1 in 4) chance to have a child with AATD in each pregnancy. People with AATD have two SERPINA1 mutations -- one in each copy of their gene. This is also called autosomal recessive inheritance, which happens equally in males and females. Any child of an AATD carrier also has a 50% chance to be a carrier, too, just like their parents. Full siblings of someone with AATD are also at risk to have the condition and should be tested.

There are different versions, or alleles, of the SERPINA1 gene (also called "PI" types). The most common allele is the "M" allele, and having two of these leads to the usual amount of alpha-1 antitrypsin in the blood and no symptoms of AATD. The "S" allele leads to medium-low levels of alpha-1 antitrypsin protein. The "Z" allele leads to very low levels of alpha-1 antitrypsin protein. Having two copies of the Z allele leads to more symptoms of AATD.

AATD carriers are those who have a mutation in one copy of their SERPINA1 gene (usually PI type "MZ" but can be "MS" or "M-Other"). Most carriers do not develop symptoms of AATD. However, recent research has shown that AATD carriers who smoke are at high risk to develop lung disease. Some AATD carriers may also have a small increased risk for liver disease. Carriers should avoid smoking and live a healthier lifestyle.

References
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Who else should be tested for alpha-1 antitrypsin deficiency?

What is the chance that I will have a child with alpha-1 antitrypsin deficiency?

Who else should be tested for alpha-1 antitrypsin deficiency?

Full siblings of someone with severe alpha-1 antitrypsin deficiency (AATD) can also have severe AATD and should be tested. Parents and children of someone with severe AATD are usually carriers. Genetic testing can be done to confirm someone's carrier status and rule out the usually low risk of having two mutations in the SERPINA1 gene (severe AATD). Any relative with chronic obstructive pulmonary disease (COPD), incompletely reversible asthma or unexplained liver disease should also be tested. The risk for more distant relatives to have AATD depends on the gene mutations in the family and the closeness of relationship.

If you want to learn whether genetic testing for AATD may be right for you or your family member, speak to your healthcare provider about a referral to see a genetic counselor near you. In the U.S., the Alpha-1 Foundation provides free telephone-based genetic counseling and you can reach this service by calling 1-800-785-3177. Genetic counselors can be found on the National Society of Genetic Counselors website.

References
  • American Thoracic Society Documents. American Thoracic Society/European Respiratory Society Statement: Standards for the Diagnosis and Management of Individuals with Alpha-1 Antitrypsin Deficiency. Am J Respir Crit Care Med. Vol 168:818-900. February 2003.
  • Alpha-1 at MUSC: A shared voice for patient empowerment. Retrieved from https://alphaoneregistry.org/.
What is the chance that I will have a child with alpha-1 antitrypsin deficiency?

Alpha-1 antitrypsin deficiency (AATD) carriers have one SERPINA1gene with a mutation and one copy without it. If two AATD carriers have children together, they have a 25% (1 in 4) chance to have a child with AATD in each pregnancy. People with AATD have two SERPINA1 mutations -- one in each copy of their gene. This is also called autosomal recessive inheritance, which happens equally in males and females. Any child of an AATD carrier also has a 50% chance to be a carrier, too, just like their parents. Full siblings of someone with AATD are also at risk to have the condition and should be tested.

There are different versions, or alleles, of the SERPINA1 gene (also called "PI" types). The most common allele is the "M" allele, and having two of these leads to the usual amount of alpha-1 antitrypsin in the blood and no symptoms of AATD. The "S" allele leads to medium-low levels of alpha-1 antitrypsin protein. The "Z" allele leads to very low levels of alpha-1 antitrypsin protein. Having two copies of the Z allele leads to more symptoms of AATD.

AATD carriers are those who have a mutation in one copy of their SERPINA1 gene (usually PI type "MZ" but can be "MS" or "M-Other"). Most carriers do not develop symptoms of AATD. However, recent research has shown that AATD carriers who smoke are at high risk to develop lung disease. Some AATD carriers may also have a small increased risk for liver disease. Carriers should avoid smoking and live a healthier lifestyle.

References

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