What is alpha-1 antitrypsin deficiency?
Alpha-1 antitrypsin (AAT) is a protein made in the liver that travels in the blood to the lungs. Its job is to protect the delicate lung tissue from enzymes released by white blood cells during inflammation. In alpha-1 antitrypsin deficiency (AATD), an inherited change in the SERPINA1 gene means that too little AAT reaches the lungs, or the protein does not work properly.
Without enough protection, the air sacs are gradually destroyed, causing emphysema, often at a younger age than usual and sometimes in people who have smoked little or not at all. In some forms, the abnormal protein also builds up inside liver cells and can damage the liver.
AATD is a rare condition and is widely under-recognised. Many people are diagnosed only after years of being treated for asthma or COPD without the underlying cause being identified. Care is coordinated with hepatology and genetics where needed.
Symptoms of AATD
Lung symptoms usually begin in the 30s to 50s, earlier in people who smoke:
- Breathlessness on exertion that gradually worsens
- Wheezing, which may be mistaken for asthma
- Chronic cough and sputum, and frequent chest infections
- Reduced exercise tolerance and fatigue
Liver involvement can cause prolonged jaundice in newborns, abnormal liver tests, or cirrhosis in adults. A rare skin condition called panniculitis, with painful lumps under the skin, is also associated with AATD.
Causes and risk factors
AATD is inherited from both parents in a co-dominant pattern. The normal gene variant is called M. The most important deficient variants are Z and S. People with two Z genes (PiZZ) have very low AAT levels and the highest risk of lung and liver disease. Those with one normal and one abnormal gene (for example PiMZ) are carriers with modestly reduced levels. They have a higher risk of lung disease mainly if they smoke.
Smoking is by far the most important factor that determines whether, and how early, emphysema develops. Exposure to dusts, fumes and indoor smoke from biomass fuels adds to the damage.
How AATD is diagnosed
International guidance from the WHO and the ATS/ERS recommends testing everyone with COPD at least once, together with adults with poorly reversible asthma, unexplained liver disease, panniculitis, bronchiectasis without another cause, or a family history of AATD.
| Test | What it shows |
|---|---|
| Serum alpha-1 antitrypsin level | Whether the blood level is low (a simple screening blood test) |
| Phenotyping or genotyping | The specific gene variants, such as PiZZ, PiSZ or PiMZ |
| Spirometry with DLCO | Airflow obstruction and damage to the gas-exchanging surface of the lung |
| CT chest | The extent and pattern of emphysema, typically worse in the lower lobes |
| Liver function tests and ultrasound | Liver involvement, including fibrosis or cirrhosis |
Because AAT rises during infection and inflammation, a borderline level is interpreted with a CRP measurement or repeated when well. Once a diagnosis is made, testing of brothers, sisters and children is offered.
AATD treatment
Stopping smoking
Complete smoking cessation is the single most important treatment and substantially slows the loss of lung function. Avoiding second-hand smoke, incense and biomass smoke, and occupational dust is also advised.
Standard emphysema treatment
Lung disease is treated in the same way as COPD: long-acting bronchodilator inhalers, inhaled steroids in selected patients with frequent exacerbations, pulmonary rehabilitation, prompt treatment of infections, and oxygen when required. Vaccination against influenza, pneumococcus, COVID-19 and hepatitis A and B is recommended.
Augmentation therapy
Intravenous augmentation therapy with purified alpha-1 antitrypsin from donated plasma raises blood and lung levels of the protein. In patients with severe deficiency and emphysema, it has been shown to slow the loss of lung tissue measured on CT. It is given as a regular infusion and is considered for non-smokers with severe deficiency. Availability and cost in India are discussed individually.
Advanced disease
Selected patients with severe emphysema may be considered for lung volume reduction procedures or for lung transplantation. Liver disease is managed with hepatology, and severe liver disease can require liver transplantation.
Outlook and follow-up
The outlook varies greatly. Many non-smokers with AATD have a near-normal life expectancy, while people who continue to smoke tend to develop severe emphysema early. Regular review with spirometry, periodic liver tests and, in some patients, CT monitoring allows treatment to be adjusted. Alcohol should be limited to protect the liver.
When to seek urgent care
Seek urgent medical attention for breathlessness at rest or rapidly worsening breathlessness, sudden sharp chest pain with breathlessness (which may indicate a collapsed lung), blue lips, drowsiness or confusion, fever with increasing sputum, yellowing of the skin or eyes, vomiting blood, or swelling of the abdomen.
Frequently asked questions
Should everyone with COPD be tested for AATD?
Yes. Current international guidance recommends that every person with COPD has their alpha-1 antitrypsin level checked at least once, as the condition is otherwise easily missed.
I have never smoked. Can I still have AATD-related emphysema?
Yes. Although smoking greatly accelerates lung damage, people with severe deficiency can develop emphysema without smoking, particularly with exposure to dusts or fumes.
Should my family be tested?
Yes. AATD is inherited, so brothers, sisters, children and sometimes parents of an affected person are offered a simple blood test. Early diagnosis allows them to avoid smoking and protect their lungs.
What is augmentation therapy?
Augmentation therapy is a regular intravenous infusion of alpha-1 antitrypsin purified from donated plasma. It raises protein levels and can slow emphysema progression in people with severe deficiency.
Can AATD affect the liver?
Yes. In some gene types the abnormal protein accumulates in the liver, which can cause jaundice in newborns and liver scarring or cirrhosis in adults. Liver tests are part of routine follow-up.
Is AATD common in India?
Severe AATD appears to be uncommon in India, but it has been reported and is probably under-diagnosed because testing is not yet routine.
Related conditions and procedures
Consult Dr. Gogineni Ratnakara Rao
Apollo Hospitals, Financial District: Monday to Saturday, 8:30 AM to 5:00 PM. Anything in Lung Clinic, Chanda Nagar: Monday to Saturday (Thursday closed), 6:00 PM to 9:00 PM.