ConditionLungs & breathing
Alpha-1 Antitrypsin Deficiency
Alpha-1 antitrypsin deficiency (AATD) is an inherited condition in which the body makes too little of a protein called alpha-1 antitrypsin (AAT), or a faulty version of it. AAT normally protects the lungs from damage by immune enzymes. Without enough, people can develop emphysema (COPD) at a young age, especially if they smoke. The faulty protein can also build up in the liver and cause liver disease in children and adults. A simple blood test diagnoses it, and quitting smoking is the most important treatment.
Also called: AATD, Alpha-1, AAT deficiency, A1AD, genetic COPD
At a glance
- What it is
- An inherited lack of a protective protein that leads to lung and liver damage.
- How common
- About 1 in 2,500 to 5,000 people of European descent; most are undiagnosed.
- Lung effects
- Emphysema, often before age 50, worse with smoking.
- Liver effects
- Jaundice in newborns, hepatitis, cirrhosis and liver cancer in adults.
- Diagnosis
- AAT blood level and genotype test.
- Treatment
- Stop smoking, standard COPD care, augmentation therapy, liver monitoring, transplant if needed.
When to get help
Call 911 or go to the ER
- Severe breathlessness, blue lips or confusion
- Vomiting blood or black stools, or sudden swelling of the belly with confusion (possible advanced liver disease)
See a doctor within a day or two
- Worsening breathlessness or cough with fever or more sputum (possible flare-up)
- Yellowing of the skin or eyes, or a newborn with prolonged jaundice beyond 2 weeks
Book a routine appointment
- Breathlessness, wheezing or a diagnosis of COPD before age 45, or in a nonsmoker
- Asthma that does not fully reverse with treatment
- Unexplained liver disease or abnormal liver tests
- A close relative diagnosed with alpha-1
What alpha-1 antitrypsin does
AAT is made in the liver and travels in the blood to the lungs. There it blocks neutrophil elastase, an enzyme white blood cells release to fight infection. Without enough AAT, elastase digests the elastic walls of the air sacs, causing emphysema. Smoke greatly increases elastase activity and inactivates the remaining AAT, which is why smokers with AATD develop severe lung disease 10 to 20 years earlier than nonsmokers.
In the most common severe variant (Z), the abnormal protein folds incorrectly and gets stuck in liver cells. The trapped protein causes inflammation and scarring. This is why the liver is affected even though blood levels are low.
Genetics
AATD is inherited in an autosomal codominant pattern. Everyone has two copies of the gene (called SERPINA1). Common versions:
| Genotype | AAT level | Risk |
|---|---|---|
| MM | Normal | Normal |
| MZ | Mildly reduced | Carrier; somewhat increased lung risk with smoking and some liver risk |
| SZ | Moderately reduced | Increased lung risk, especially with smoking |
| ZZ (PI*ZZ) | Severely reduced | High risk of emphysema and liver disease |
| Null variants | Absent | High lung risk, no liver accumulation |
Children of two carriers have a 1 in 4 chance of severe deficiency. Relatives of someone diagnosed should be offered testing.
Symptoms
Lungs
- shortness of breath on exertion, often starting in the 30s to 40s
- wheezing and frequent chest infections
- chronic cough and sputum
- reduced exercise tolerance
- bronchiectasis in some people
Emphysema in AATD typically affects the lower lungs, unlike smoking-related emphysema.
Liver
- prolonged jaundice, poor feeding or bleeding in newborns
- abnormal liver tests in children or adults
- in adults: fatigue, cirrhosis, fluid in the belly, jaundice and an increased risk of liver cancer
Skin
Panniculitis, painful lumps under the skin, is a rare complication.
Who should be tested
Guidelines recommend testing everyone with:
- COPD or emphysema, regardless of age or smoking history
- asthma that does not fully respond to treatment
- unexplained liver disease
- necrotizing panniculitis or certain types of vasculitis
- a family member with AATD
Diagnosis
- AAT blood level: a low level suggests deficiency.
- Genotype or phenotype test to identify the variant. Some tests use a finger-prick blood spot.
- Lung tests: spirometry, lung volumes, diffusion capacity and CT chest to assess emphysema.
- Liver tests: liver blood tests, ultrasound and elastography (FibroScan) to measure scarring.
Treatment
Lungs
- Stop smoking. This is the single most effective step and slows lung function decline dramatically. Avoid secondhand smoke, dust and fumes.
- Standard COPD treatment: inhaled bronchodilators, pulmonary rehabilitation, oxygen if levels are low. See COPD.
- Vaccinations: flu, pneumococcal, COVID-19 and RSV as recommended.
- Augmentation therapy: weekly IV infusions of AAT purified from donated plasma for people with severe deficiency and emphysema. It slows loss of lung tissue on CT scans.
- Lung volume reduction or lung transplant for advanced disease.
Liver
- Avoid alcohol and maintain a healthy weight.
- Get vaccinated against hepatitis A and B.
- Have regular liver monitoring, and liver cancer screening with ultrasound if cirrhosis develops.
- Liver transplant for liver failure, which also cures the deficiency because the new liver makes normal AAT.
Augmentation therapy does not help the liver. Treatments aimed at reducing the faulty protein in the liver are in clinical trials.
Outlook
Many people with AATD who never smoke have near-normal life expectancy. Smoking shortens life considerably. Early diagnosis allows lifestyle changes, monitoring and treatment before significant damage occurs, and testing of relatives.
Frequently asked questions
What are the symptoms of alpha-1 antitrypsin deficiency?
The most common symptoms are shortness of breath, wheezing, cough and frequent chest infections, often starting before 45. Liver involvement can cause jaundice in newborns and, in adults, fatigue, abdominal swelling and signs of cirrhosis. Some people have no symptoms.
How is alpha-1 antitrypsin deficiency diagnosed?
A blood test measures the level of AAT, and a genetic test identifies which variants you carry. Lung function tests, a chest CT scan and liver tests show whether organs are affected. Testing is simple and recommended for everyone with COPD.
Can you live a normal life with alpha-1?
Many people can, especially if diagnosed early and they never smoke. Avoiding smoke and alcohol, staying active, getting vaccinated and having regular lung and liver checks greatly reduce the risk of serious disease.
Is being an alpha-1 carrier dangerous?
Carriers (usually MZ) have mildly reduced AAT levels. Most never develop disease, but they have a higher risk of lung damage if they smoke and a modestly higher risk of liver disease with other liver stresses such as alcohol or fatty liver.
Sources
This guide was written from current patient and clinical guidance, including:
- Alpha-1 Foundation: Alpha-1 antitrypsin deficiency clinical practice guidelines
- American Thoracic Society/European Respiratory Society: Standards for the diagnosis and management of AATD
- MedlinePlus Genetics: Alpha-1 antitrypsin deficiency
- Global Initiative for Chronic Obstructive Lung Disease (GOLD): Report
- American Liver Foundation: Alpha-1 antitrypsin deficiency