Published: 18 Jun 2025

ICD9: 273.4      ICD10: E88.01      ICD11: 5C5A

Alpha-1 Antitrypsin Deficiency (AATD) is a genetic condition that can cause lung disease, liver disease, and, less commonly, skin problems.
It's caused by a deficiency or absence of a protein called alpha-1 antitrypsin (AAT).

Here's a breakdown:

What is Alpha-1 Antitrypsin (AAT)?
AAT is a protein made in the liver.
Its primary function is to protect the lungs from damage caused by enzymes, particularly elastase. Elastase is released by white blood cells to fight infection and digest damaged tissue. AAT acts as an inhibitor, controlling elastase and preventing it from breaking down healthy lung tissue.

What happens in AATD?
Lung Disease (Emphysema): The lack of AAT allows elastase to break down the delicate structures of the lungs, leading to emphysema (a type of chronic obstructive pulmonary disease or COPD). The destruction of air sacs (alveoli) makes it difficult to breathe. This damage can occur even in people who don't smoke, but it's much more severe in smokers.
Liver Disease: The most common AAT mutation causes the abnormal AAT protein to become trapped in the liver cells, preventing its release into the bloodstream. This buildup can damage the liver and lead to cirrhosis (scarring of the liver), liver failure, or even liver cancer. Liver problems can occur in both children and adults with AATD.
Less Common Problems: Some individuals with AATD may experience skin conditions like panniculitis (inflammation of the fat layer under the skin).

Cause of AATD:
AATD is a genetic condition, meaning it's inherited from parents.
The gene responsible for making AAT is called *SERPINA1*.
Individuals inherit two copies of the *SERPINA1* gene, one from each parent.
If a person inherits two abnormal *SERPINA1* genes, they will likely have AATD. If they inherit one normal and one abnormal gene, they are typically carriers, meaning they usually don't develop severe symptoms but can pass the abnormal gene on to their children.

Symptoms:
Lung Disease:
Shortness of breath, especially with exertion
Wheezing
Chronic cough
Frequent respiratory infections
Early-onset emphysema (often in the 30s or 40s, especially in smokers)
Liver Disease:
Jaundice (yellowing of the skin and eyes)
Swollen abdomen
Fatigue
Nausea and vomiting
Dark urine
Pale stools
Skin:
Painful, red, inflamed nodules under the skin (panniculitis)

Diagnosis:
A blood test to measure AAT levels.
Genetic testing to identify specific *SERPINA1* gene mutations.
Liver function tests (if liver problems are suspected).
Pulmonary function tests (to assess lung function).
Liver biopsy (in some cases of liver disease).

Treatment:
Augmentation Therapy: Involves intravenous infusions of purified AAT protein derived from human plasma. This aims to increase AAT levels in the blood and protect the lungs.
Bronchodilators: Medications to open up the airways and make breathing easier (like those used for asthma and COPD).
Inhaled Corticosteroids: To reduce inflammation in the airways.
Antibiotics: To treat respiratory infections.
Oxygen Therapy: For individuals with severe emphysema.
Pulmonary Rehabilitation: A program to help people with lung disease improve their breathing and overall quality of life.
Lung Transplant: In severe cases of lung disease.
Liver Transplant: In severe cases of liver disease.
Lifestyle Modifications:
Avoid smoking: Smoking significantly accelerates lung damage in AATD.
Avoid lung irritants: Such as dust, fumes, and air pollution.
Vaccinations: Get vaccinated against influenza and pneumococcal pneumonia to prevent respiratory infections.
Maintain a healthy weight: Being overweight or underweight can worsen lung problems.
Treatment of Panniculitis: Can include antibiotics or other medications to reduce inflammation.

Important Considerations:
Early diagnosis is crucial: Early intervention can help slow the progression of lung and liver disease.
Genetic counseling: Is important for individuals with AATD and their families, especially if they are planning to have children.
Screening family members: It's recommended that family members of individuals with AATD be screened for the condition, as they may also be affected or carriers.

In summary, Alpha-1 Antitrypsin Deficiency is a genetic disorder where a deficiency in the AAT protein leads to lung and/or liver damage. Understanding the condition, getting diagnosed early, and following appropriate treatment plans are vital for managing the disease and improving the quality of life for affected individuals.