Alpha-1 Antitrypsin Deficiency

Overview

Alpha-1 antitrypsin is a protein made mainly in the liver that travels to the lungs, where it protects delicate lung tissue from being damaged by other enzymes. Alpha-1 antitrypsin deficiency is an inherited condition in which the body produces too little of this protein, or a faulty version that does not work properly and can build up in the liver.

Because the protein is not available to protect the lungs, people with this deficiency are at higher risk of developing lung damage and emphysema, often at a younger age than usual, especially if they smoke. The abnormal protein trapped in the liver can also cause liver disease in some people. Symptoms and severity vary widely, and some people are never significantly affected. Recognizing the condition matters because avoiding smoking and other steps can greatly reduce harm.

Symptoms

Symptoms depend on whether the lungs, liver, or both are affected, and they vary widely in severity and age of onset.

• Lung symptoms: Shortness of breath, wheezing, a long-lasting cough, frequent chest infections, and reduced exercise tolerance, often resembling COPD.
• Liver symptoms: Yellowing of the skin or eyes (jaundice), swelling of the abdomen or legs, fatigue, and easy bruising, which can occur in infants, children, or adults.
• Unexplained chronic liver problems or lung disease, sometimes appearing at a younger age than expected

Many people develop lung symptoms in adulthood, while liver involvement can appear at any age, including occasionally in newborns.

Causes

Alpha-1 antitrypsin deficiency is caused by inherited changes in the gene that makes the alpha-1 antitrypsin protein.

• Genetic inheritance: A person inherits one copy of the gene from each parent. Certain altered copies lead to low or faulty protein.
• Inheritance pattern: The condition follows a pattern in which inheriting two altered copies usually causes more significant deficiency, while one altered copy may cause a milder effect or none.
• Faulty protein build-up: Some abnormal forms of the protein become trapped in the liver, where they can cause damage, while too little reaches the lungs to protect them.

Smoking and exposure to lung irritants greatly accelerate lung damage in people with the deficiency, making them a major factor in how the condition develops.

Risk Factors

• A family history of alpha-1 antitrypsin deficiency or early lung or liver disease
• Inheriting two altered copies of the responsible gene
• Smoking, which dramatically worsens lung damage
• Exposure to dust, fumes, and other lung irritants
• Developing emphysema or COPD at a younger age or without a smoking history

Diagnosis

The condition is often suspected when lung or liver disease appears unusually early or without the usual causes, and is confirmed with specific tests.

• Blood test for the protein: Measuring the level of alpha-1 antitrypsin in the blood.
• Genetic testing: To identify the specific gene changes and confirm the diagnosis.
• Lung function tests: To assess any breathing impairment.
• Liver tests and imaging: Blood tests and scans to check for liver damage.

Testing is also recommended for close relatives of someone diagnosed, since the condition is inherited.

Treatment

There is no cure, but treatment can protect the lungs and liver, relieve symptoms, and slow damage. The most important single step is avoiding smoking.

• Not smoking: Stopping or never starting smoking is the most important measure to protect the lungs.
• Lung treatments: Inhalers and other medicines used for COPD, pulmonary rehabilitation, vaccinations to prevent chest infections, and oxygen if needed.
• Augmentation therapy: For some people with lung disease, regular infusions of alpha-1 antitrypsin protein may be used to raise protein levels.
• Liver care: Monitoring liver health, avoiding alcohol and other liver stressors, and managing complications; severe liver disease may require a liver transplant.
• Lung transplant: Considered in advanced lung disease in selected people.

A care team often includes lung and liver specialists, and treatment is tailored to which organs are affected.

Prevention

• Never smoke, and avoid secondhand smoke and lung irritants such as dust and fumes
• Limit or avoid alcohol to protect the liver
• Stay up to date with vaccines that help prevent chest infections
• Attend regular check-ups to monitor lung and liver health
• Consider testing for close relatives if someone in the family is affected

The deficiency itself cannot be prevented, but its complications can often be greatly reduced.

When to See a Doctor

See a doctor if you develop breathing problems, a long-lasting cough, or signs of liver trouble such as jaundice or abdominal swelling, especially at a younger age, without smoking, or with a family history of lung or liver disease. Seek emergency care for:

• Severe shortness of breath or sudden difficulty breathing
• Coughing up blood
• Vomiting blood, black tarry stools, or severe abdominal swelling with confusion, which can signal serious liver complications

Related Topics

Frequently Asked Questions

References

1. National Heart, Lung, and Blood Institute (NHLBI). Alpha-1 Antitrypsin Deficiency.
2. MedlinePlus, U.S. National Library of Medicine. Alpha-1 antitrypsin deficiency.
3. Mayo Clinic. Alpha-1 antitrypsin deficiency.
4. American Lung Association. Alpha-1 antitrypsin deficiency.