Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that may increase the risk of lung disease and other conditions. People with AATD lack the protective protein alpha-1 antitrypsin (AAT). This makes them more susceptible to developing certain conditions. There is currently no cure for AATD, but treatments can help slow and manage complications.
AATD is an inherited condition that increases the risk of lung and liver disease. It occurs worldwide, but the prevalence varies in populations. Some evidence suggests that it affects roughly 1 in 1,500–3,500 people with European ancestry.
People with AATD may receive a misdiagnosis of a lung condition such as asthma or receive no diagnosis at all.
Symptoms may vary based on the condition itself, and getting a thorough diagnosis of the complications may help lead to the diagnosis of AATD.
Avoiding certain environmental exposures and receiving augmentation therapy may help slow the condition.
This article will discuss AATD — including its symptoms, causes, risk factors, and treatment options — in more detail.
The symptoms of AATD will vary from person to person. Some people may not experience any symptoms at all. Typically, people develop the first signs and symptoms of AATD between the ages of
The earliest symptoms usually include:
- shortness of breath or difficulty breathing
- less ability for physical activity
- weight loss
- frequent lung infections
- a rapid heartbeat
Many of the more common symptoms relate to problems with the lungs or liver. The Genetic and Rare Diseases Information Center notes that 80–99% of people with AATD have symptoms of emphysema and liver failure.
In rare cases, a person may develop dermatological symptoms such as panniculitis. This refers to the inflammation of the fat underneath the skin. The National Organization for Rare Disorders notes that only about 1 in 1,000 people with a severe form of deficiency may develop these symptoms.
AATD is a rare genetic condition. It
The liver cells create AAT and send it to various organs, such as the lungs, via the bloodstream. The function of AAT is to protect against damage and inflammation from an overactive immune system. Without it, the immune system may make a person more susceptible to organ damage.
AATD is an inherited condition, meaning that people pass it through their genes. If a person receives a mutated AAT gene from each parent, they will develop AATD. Some people who receive one mutated gene may experience some AATD complications.
The most common mutations that cause AATD are called PiZ and PiS.
Although AATD can affect people of any race or ethnicity, it seems to occur most often in white people of European ancestry. AATD is an inherited mutation, meaning that having a close relative with it increases a person’s risk of developing the condition themselves.
Additionally, some environmental and lifestyle factors may make the symptoms worse or make them appear sooner.
Smoking tobacco is a major risk factor for lung conditions and may worsen the symptoms of AATD deficiency or cause them to appear sooner. Exposure to environmental toxins — such as inhaling chemicals, dust, exhaust fumes, or other toxic substances — may also damage the lungs over time.
Similarly, alcohol use may damage the liver. In a person with AATD who is dealing with liver damage, this may be an additional risk factor.
There is currently no cure for AATD. Treatment aims to slow damage to the organs and control or treat complications.
Treatment will vary in each case. Working with a team of specialists in each damaged area may help ensure that the person receives adequate treatment in each area.
The only specific AATD treatment is an infusion of alpha1-proteinase inhibitor (Prolastin). Some doctors refer to this as augmentation therapy. This involves a person receiving an infusion of purified AAT protein from blood donors. This adds AAT to the blood and helps slow organ damage.
These infusions are generally well-tolerated. The person may require infusions all their life, generally on a weekly basis.
Doctors will treat liver and lung issues due to AATD as they would treat the issues themselves. For example, treatment for emphysema from AATD is the same as it is for other forms of chronic obstructive pulmonary disease (COPD).
Depending on the complication from AATD, the person may need various additional therapies, such as:
- oxygen therapy
- inhaled steroids
- pulmonary rehabilitation
- lung transplants
- liver transplants
Doctors may also recommend making some lifestyle changes to help improve health. For example, they may suggest that people quit or reduce smoking, reduce their exposure to secondhand smoke, and limit their alcohol intake. They might also recommend getting regular exercise to keep the lungs healthy and functioning.
Doctors may also suggest preventive measures such as vaccinations to help protect against potential recurring infections.
Diagnosis may take time in some cases, depending on how the symptoms present. For example, some people may be unaware that they have AATD until they start having problems related to their lungs at 30–40 years of age, or earlier if they smoke.
One 2020 review notes that AATD is underdiagnosed and recommends testing specific groups of people, such as those with:
- liver disease
- asthma that does not respond to treatment
- C-ANCA vasculitis, which is an autoimmune condition of the blood vessels
- panniculitis, or symptoms resulting from inflammation in the fat layer underneath the skin
- bronchiectasis, which refers to widening and damage in the bronchial tubes
A doctor may perform several tests to diagnose AATD. These can include:
- Medical history and physical exam: A doctor may ask about risk factors such as smoking. They may also ask about relatives with AATD, lung conditions, or liver diseases and about the symptoms a person is experiencing. They will also perform a physical exam, during which they may listen to the lungs.
- Diagnostic tests: A doctor may suggest a blood test to measure the level of AAT protein in the blood. They may also perform a genetic test to confirm the AATD diagnosis.
- Lung tests: If a person has a lung condition related to AATD, a doctor may recommend lung function and imaging tests to show how well the lungs are working and determine whether or not a person has other lung conditions.
The life expectancy of someone with AATD can vary widely based on a number of factors, such as when they receive the diagnosis, how any lung or liver damage progresses, and how well they respond to treatment and lifestyle changes.
One 2018 study notes that most people with a severe deficiency have a lower life expectancy than those in the general population.
Early diagnosis and treatment are key to improving life expectancy, as they help control damage via treatment and lifestyle changes to avoid other sources of damage, such as tobacco, alcohol, and environmental pollutants.
The outlook for a person with AATD who responds well to treatment, controls damage to their liver and lungs, and makes lifestyle changes to support their health is generally good.
People can find more information about the condition — such as advancements in therapy, support groups, and financial support — from:
- National Organization for Rare Disorders
- Alpha-1 Foundation
- Patient Services Incorporated
Genetic Testing Registry
- clinical trials
AATD is a rare genetic condition that can cause damage to the lungs and liver. It occurs when the body produces too little AAT, which is a protein that protects organs from damage.
Many people may not present any symptoms until adulthood, and some may not present any symptoms at all. Common symptoms include those that affect the lungs or liver, such as emphysema or liver disease.
Diagnosis can be difficult, but getting an early diagnosis is key to managing and treating the condition.
Treatment typically involves augmentation therapy with Prolastin and making certain lifestyle changes.