What is Alpha 1-antitrypsin deficiency

Alpha 1-antitrypsin deficiency (AATD) is a genetic condition that occurs when the body does not produce enough of the protein alpha-1 antitrypsin, leading to increased risk of lung and liver disease. This deficiency prevents the lungs from being protected against inflammation and enzymes, often resulting in premature emphysema or chronic liver damage.

What exactly is Alpha 1-antitrypsin deficiency?

Alpha 1-antitrypsin deficiency is an inherited disorder characterized by a lack of the alpha-1 antitrypsin (AAT) protein, which is primarily produced in the liver. Under normal circumstances, this protein travels through the bloodstream to protect healthy tissues—especially the lungs—from damage caused by infections or environmental pollutants like cigarette smoke. When a person has Alpha 1-antitrypsin deficiency, the dysfunctional AAT protein often builds up inside liver cells, causing damage there, while simultaneously failing to provide the necessary protection for the lungs, leading to tissue breakdown.

Which body systems are primarily affected?

The primary organs involved in Alpha 1-antitrypsin deficiency are the lungs and the liver. Because the AAT protein is meant to neutralize an enzyme called neutrophil elastase, a deficiency allows this enzyme to break down lung tissue unchecked, leading to early-onset emphysema. In the liver, the accumulation of abnormal, misfolded AAT protein can cause inflammation, scarring (cirrhosis), and in some cases, an increased risk of liver cancer. While less common, some individuals may also experience skin conditions like panniculitis.

How common is this condition and who is affected?

Alpha 1-antitrypsin deficiency is often underdiagnosed, but it is estimated to affect approximately 1 in 1,500 to 3,500 individuals of European descent. It is a genetic condition, meaning it is present from birth, though symptoms typically manifest in adulthood. Key factors regarding the patient population include:

• Age of onset: Lung symptoms often appear between ages 20 and 50, while liver symptoms can occur in childhood or later in life.


• Gender: Men and women are affected equally.


• Geographic factors: The condition is most prevalent in populations with Northern European ancestry, though it can occur in any ethnic group.


• Community Insight: Currently, 339 people with Alpha 1-antitrypsin deficiency have joined the DiseaseMaps.org community to share their experiences and support one another.

How is Alpha 1-antitrypsin deficiency classified?

The severity of Alpha 1-antitrypsin deficiency is determined by the specific genetic mutations inherited from one's parents. The gene responsible is the SERPINA1 gene. Geneticists classify individuals based on their "Pi" (protease inhibitor) type:

1. PiMM: The most common genotype, representing normal AAT protein levels.


2. PiZZ: The most severe form, where individuals have very low levels of the protective protein and are at high risk for both lung and liver disease.


3. PiSZ or PiMZ: Intermediate forms where protein levels may be reduced, carrying a variable risk depending on environmental factors like smoking.

Next steps

• Consult a pulmonologist or hepatologist to discuss baseline lung function tests and liver enzyme screenings.


• Request a blood test specifically for AAT levels and phenotype (genotyping) if you suspect you are at risk.


• Avoid smoking and environmental pollutants, which drastically accelerate lung damage in those with Alpha 1-antitrypsin deficiency.


• Connect with the 339 community members at DiseaseMaps.org to share experiences and learn about ongoing clinical trials.

Medical disclaimer: This information is for educational purposes only and does not constitute medical advice, diagnosis, or treatment; always consult with a qualified healthcare professional regarding your specific health needs.

References

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


• Orphanet: Alpha-1 antitrypsin deficiency (ORPHA:97).


• OMIM (Online Mendelian Inheritance in Man): SERPINA1 Gene Entry #107400.


• Alpha-1 Foundation: Patient resources and disease education.