AATD 101: Symptoms, Testing and Treatment for Alpha-1 Antitrypsin Deficiency

November is Alpha-1 Awareness Month, a time to shine a light on one of the most underdiagnosed inherited conditions in the United States. Alpha-1 antitrypsin deficiency (AATD) can lead to serious lung and liver disease. Many people live with it for years before anyone thinks to test for it.

A Missing Protein That Protects the Lungs

Alpha-1 antitrypsin (AAT) is a protein made mainly in the liver. Its job is to protect the lungs from neutrophil elastase, an enzyme the immune system releases to fight infection. Without enough AAT, that enzyme can damage lung tissue over time.

In AATD, changes in a gene called SERPINA1 lead to too little AAT or an abnormal form of the protein. The abnormal protein can also become trapped in the liver, where it accumulates and causes damage. MedlinePlus Genetics explains that this is why AATD can affect both organs.

How AATD Is Inherited

Everyone inherits two copies of the AAT gene, one from each parent. The most common version, called M, makes normal amounts of the protein. The Z version makes very little, and the S version makes moderately low amounts.

People with two Z copies (PiZZ) have the severe form of AATD and the highest risk of lung and liver disease. People with one Z copy and one normal copy (MZ) are carriers. They may have a slightly higher risk of lung or liver problems, especially if they smoke. According to MedlinePlus, an estimated 185 million people worldwide carry one S or Z copy.

AATD affects about 1 in 1,500 to 3,500 people of European ancestry. A 2026 review in the Cleveland Clinic Journal of Medicine estimates that roughly 100,000 Americans have the severe form, and fewer than 15% of them have been diagnosed.

Symptoms Often Mistaken for Asthma or COPD

Lung symptoms usually begin between ages 25 and 50. They may include the following:

• Shortness of breath after mild activity
• Wheezing
• Reduced ability to exercise
• Frequent chest infections or bronchitis

Over time, many people develop emphysema. Smoking or exposure to tobacco smoke speeds up lung damage. Because these symptoms look like asthma or chronic obstructive pulmonary disease (COPD), AATD is often missed. The Cleveland Clinic review notes that diagnosis typically takes five to eight years from the first symptoms and that longer delays have been linked to worse outcomes.

AATD can also affect the liver. According to MedlinePlus, about 10% of infants with AATD develop liver disease, often with jaundice. About 15% of adults with the condition develop cirrhosis, and the risk of liver cancer is higher. Rarely, AATD causes panniculitis, a skin condition with painful lumps or patches.

Who Should Be Tested

AATD is diagnosed with a blood test that measures AAT levels. Doctors often follow up with phenotyping or genetic testing to identify which gene variants a person has.

Experts recommend testing at least once for anyone with the following:

• COPD, emphysema or chronic bronchitis
• Asthma with breathing problems that don’t fully improve with treatment
• Unexplained liver disease
• Unexplained bronchiectasis
• Necrotizing panniculitis
• A parent, sibling or child with AATD

AlphaNet adds recurrent pneumonia and a family history of emphysema or liver disease to that list.

Treatment and Everyday Management

There is no cure for AATD yet, but treatment can help protect the lungs. According to the American Lung Association, augmentation therapy raises AAT levels using protein from donated human plasma. It’s usually given as a weekly IV infusion to people with the lowest AAT levels. It can’t reverse existing damage, but it may slow further lung damage. It doesn’t treat AATD-related liver disease.

Other steps include the following:

• Quitting smoking and avoiding secondhand smoke, dust and workplace fumes
• Avoiding alcohol to protect the liver
• Using standard COPD treatments, oxygen therapy and pulmonary rehabilitation as needed
• Talking with a doctor about medications that can affect the liver

People with advanced lung or liver disease may be referred for a transplant.

Research is moving quickly. RNA-based therapies and gene-editing approaches that aim to fix or silence the faulty gene are in clinical trials, according to the Cleveland Clinic review.

This Alpha-1 Awareness Month, the most important step may be the simplest: If you have COPD, hard-to-control asthma, unexplained liver disease or a family history of AATD, ask your doctor whether you should be tested.