Is Alpha 1-antitrypsin deficiency hereditary?

Alpha 1-antitrypsin deficiency is a hereditary genetic disorder caused by mutations in the SERPINA1 gene that result in the liver producing low levels of a protective protein. Because it is inherited from both parents, it follows an autosomal codominant inheritance pattern, meaning children who inherit two abnormal gene copies are at significant risk for developing lung and liver disease.

Is Alpha 1-antitrypsin deficiency hereditary?

Yes, Alpha 1-antitrypsin deficiency is strictly a hereditary condition, meaning it is passed down from parents to children through DNA. It is not contagious, nor can it be acquired through lifestyle choices; it is present from birth. In medical terms, it is both genetic (caused by a change in the DNA sequence) and hereditary (inherited from one's parents). While most people have two "M" alleles (the normal gene), individuals with Alpha 1-antitrypsin deficiency carry variants—most commonly the "S" or "Z" alleles—that disrupt the production or function of the alpha-1 antitrypsin protein.

What is the inheritance pattern of Alpha 1-antitrypsin deficiency?

Alpha 1-antitrypsin deficiency follows an autosomal codominant inheritance pattern. Unlike typical recessive disorders, both inherited alleles contribute to the person's phenotype. If an individual inherits one normal allele and one abnormal allele (such as MS or MZ), they are typically carriers with sufficient protein levels. However, if they inherit two abnormal alleles (such as ZZ), they are at high risk for clinical disease. De novo (spontaneous) mutations are extremely rare in Alpha 1-antitrypsin deficiency; the vast majority of cases are inherited from parents who are either carriers or have the condition themselves.

What are the risks to children of an affected parent?

When both parents are carriers of the Alpha 1-antitrypsin deficiency gene (e.g., both are MZ), the risks for each pregnancy are as follows:

• 25% chance the child will have two normal alleles (MM).


• 50% chance the child will be a carrier (MZ), generally showing no clinical symptoms but capable of passing the gene to their own children.


• 25% chance the child will inherit two abnormal alleles (ZZ), which is the genotype most strongly associated with severe Alpha 1-antitrypsin deficiency and clinical complications.

How is genetic testing and counseling utilized?

Genetic testing for Alpha 1-antitrypsin deficiency is performed via a simple blood test that analyzes the SERPINA1 gene to determine the individual's genotype. Clinical geneticists recommend testing for family members of anyone diagnosed with the condition, particularly siblings and children. Genetic counseling is a vital step in this process, as it helps families understand the inheritance risks, interpret test results, and navigate reproductive options. For those planning pregnancies, options such as preimplantation genetic testing (PGT) or prenatal diagnosis via chorionic villus sampling (CVS) or amniocentesis may be discussed to determine the status of a developing fetus.

Next steps

• Consult with a medical geneticist or a pulmonologist/hepatologist to discuss your specific genotype.


• Encourage first-degree relatives to undergo genetic testing to assess their risk levels.


• Join the Alpha 1-antitrypsin deficiency community on DiseaseMaps.org to connect with 339 other members who share lived experiences.


• Request a referral to a genetic counselor to discuss family planning and inheritance probabilities.

Medical disclaimer: This content is for informational purposes only and does not constitute professional medical advice, diagnosis, or treatment; always seek the advice of your physician or other qualified health provider with any questions regarding a medical condition.

References

• NIH Genetic and Rare Diseases (GARD) Information Center: Alpha-1 antitrypsin deficiency.


• Orphanet: Alpha-1 antitrypsin deficiency (ORPHA:73).


• OMIM (Online Mendelian Inheritance in Man): SERPINA1 gene entry (#107400).


• Alpha-1 Foundation: Genetic testing and counseling resources.