Alpha-1 Antitrypsin Deficiency
AATD, Alpha-1, Inherited emphysema, Genetic COPD, Genetic emphysema
Alpha-1 antitrypsin deficiency is a genetic condition that can lead to serious lung and liver damage. While there is no cure, understanding the condition and taking the right steps can help people with Alpha-1 manage their symptoms and maintain a good quality of life.
Table of contents
- What is Alpha-1 Antitrypsin Deficiency?
- What Causes Alpha-1 Antitrypsin Deficiency?
- Who is Affected?
- How Alpha-1 Affects the Lungs and Liver
- Signs and Symptoms
- Diagnosis and Testing
- Treatment Options
- Living with Alpha-1: Lifestyle Changes
- Outlook and Life Expectancy
What is Alpha-1 Antitrypsin Deficiency?
Alpha-1 antitrypsin deficiency (often called “Alpha-1”) is an inherited genetic disorder that causes the body to produce low levels of a protective protein called alpha-1 antitrypsin (AAT)[1]. This protein is made by the liver and travels through the bloodstream to protect the lungs from damage[2].
When someone has Alpha-1, their body either doesn’t make enough of this protein, makes a faulty version of it, or the protein gets trapped in the liver instead of reaching the lungs[3]. Without enough working alpha-1 antitrypsin in the lungs, people with this condition face an increased risk of developing serious diseases, including emphysema (damaged air sacs in the lungs), cirrhosis (liver scarring), and, less commonly, panniculitis (a skin condition)[1].
What Causes Alpha-1 Antitrypsin Deficiency?
Alpha-1 antitrypsin deficiency is a genetic disorder caused by changes, or variants, in the SERPINA1 gene[3]. This gene carries the instructions for making the alpha-1 antitrypsin protein. These gene changes are inherited from parents, so Alpha-1 tends to run in families[6].
People inherit two copies of the SERPINA1 gene, one from each parent. Researchers have found more than 120 different variants of this gene that are linked to Alpha-1[2]. The most common version of the gene is called M, which produces normal levels of alpha-1 antitrypsin. Other versions, such as S and Z, produce reduced levels. The Z version produces very little of the protein[6].
If you have two abnormal copies of the gene (such as ZZ), you have Alpha-1 deficiency and are at higher risk of developing lung or liver disease before age 45[3]. If you have one abnormal copy and one normal copy (such as MZ), you are a carrier of Alpha-1. Carriers have a slightly higher risk of developing lung disease, especially if they smoke, and can pass the abnormal gene to their children[3].
The condition is inherited in an autosomal codominant pattern, which means that both versions of the gene may be active and both contribute to the trait[6].
Who is Affected?
Alpha-1 antitrypsin deficiency occurs worldwide, but how common it is varies by population[6]. It is one of the most common genetic disorders among people with European ancestry, but uncommon in people of Asian descent[1].
About 1 in 25 people of European descent have at least one abnormal copy of the gene for Alpha-1[1]. In the United States, about 1 in 3,500 people have two abnormal copies of the gene, putting them at risk for severe organ damage[1]. The condition affects approximately 1 in 1,500 to 3,500 individuals with European ancestry globally[6].
Many people with Alpha-1 are likely undiagnosed, particularly those who have a lung condition called chronic obstructive pulmonary disease (COPD). About 3% of people with COPD are believed to have Alpha-1, but the underlying deficiency is often never identified[8]. Some people are even misdiagnosed with asthma[6].
People of any racial or ethnic group can get Alpha-1, but it is more common in people of northern European and Iberian backgrounds[7].
How Alpha-1 Affects the Lungs and Liver
- Lungs
- Liver
Alpha-1 antitrypsin is a protein that forms in the liver and then moves through the bloodstream to the lungs, where it protects lung tissue from damage[1]. It works like an “off switch” for an enzyme called neutrophil elastase. This enzyme is released by white blood cells to fight infections in the lungs, but it can also destroy healthy lung tissue if left unchecked[1].
When gene mutations cause low levels of alpha-1 antitrypsin or create an incorrectly shaped version of the protein, there isn’t enough of it in the lungs to stop neutrophil elastase. The enzyme then starts breaking down elastin, a protein that gives strength and flexibility to the small air sacs in the lungs called alveoli[1]. Elastin allows the alveoli to stretch and contract like a rubber band. Without enough elastin, the alveoli lose their shape and become floppy, making it difficult to breathe and get oxygen properly. This damage is called emphysema[1].
In some cases, gene mutations change the shape of the alpha-1 antitrypsin protein in a way that prevents it from leaving the liver. The abnormal protein builds up in liver cells over time, which can cause scarring and damage to the liver[1]. Since the protein can’t escape the liver, it’s also unable to reach the bloodstream and lungs to provide protection there[1].
Signs and Symptoms
Some people with Alpha-1 antitrypsin deficiency do not have any symptoms[3]. The signs and symptoms of the condition, and the age at which they appear, vary greatly among individuals[6]. Symptoms can even vary within the same family[2].
Lung Symptoms
People with Alpha-1 usually develop the first signs and symptoms of lung disease between the ages of 20 and 50[6]. Lung symptoms are often similar to those of chronic obstructive pulmonary disease (COPD) or emphysema[1]. These symptoms may include:
- Shortness of breath, especially during physical activity or exertion[1]
- Wheezing (a whistling sound when breathing)[1]
- Chronic cough, often producing mucus or phlegm[1]
- Extreme tiredness or fatigue[1]
- Repeated respiratory infections such as colds and the flu[3]
- Frequent chest colds[1]
- Chest pain[3]
- Reduced ability to exercise[6]
- Unintentional weight loss[6]
Smoking or exposure to tobacco smoke greatly accelerates the appearance of emphysema symptoms and damage to the lungs in people with Alpha-1[6]. Environmental factors such as exposure to chemicals and dust also impact the severity of the condition[6].
Liver Symptoms
About 10% of infants and 15% of adults with Alpha-1 develop liver disease[1]. Liver disease is more common in children who have Alpha-1 antitrypsin deficiency[3]. In newborns, Alpha-1 can result in early onset jaundice followed by prolonged jaundice[8].
Signs and symptoms of liver damage include:
Some adults develop liver damage, called cirrhosis, due to the formation of scar tissue in the liver[6]. Individuals with Alpha-1 are also at increased risk of developing a type of liver cancer called hepatocellular carcinoma[6].
Skin Symptoms
Rarely, Alpha-1 antitrypsin deficiency can cause a skin condition called panniculitis, which is characterized by hardened skin with painful lumps or patches[6]. Panniculitis varies in severity and can occur at any age[6].
Diagnosis and Testing
Alpha-1 antitrypsin deficiency can be difficult to diagnose, and diagnosis often occurs late—sometimes more than five years after lung disease symptoms begin[12]. Many individuals with Alpha-1 remain undiagnosed[6].
Your healthcare provider may test you for Alpha-1 if you have[3]:
- Symptoms of Alpha-1 antitrypsin deficiency
- A condition that could be related to Alpha-1, such as emphysema or chronic obstructive pulmonary disease (COPD), especially if it started before age 55[12]
- Relatives who have Alpha-1
- Relatives who have lung or liver disease that could be related to Alpha-1
In babies, Alpha-1 often affects the liver. Your baby may need Alpha-1 testing if he or she has signs of liver disease such as jaundice or abnormal liver enzyme tests[3].
Blood Tests
A blood test can measure the level of alpha-1 antitrypsin protein in your blood[3]. If the level is lower than normal, it is likely that you have Alpha-1 deficiency[3].
Genetic Tests
A genetic test is the most certain way to check for Alpha-1 antitrypsin deficiency and should be done to confirm the results of the blood test[3]. There are two types of genetic tests[3]:
- A genotype test looks for the more common types of gene changes that can cause Alpha-1
- A phenotype test checks which type of alpha-1 antitrypsin protein your body makes
A genetic counselor can explain your test results and what the gene variants mean[12]. Genetic testing isn’t for everyone. Before you decide to be tested, talk with a genetic counselor about the mental health impact the test results might have[12].
Additional Tests
If you or your child has a low level of alpha-1 antitrypsin protein, your healthcare provider might suggest other tests to check for possible complications of the disease[12]. These tests could include:
- Lung function tests (such as spirometry) to tell how well your lungs are working[12]
- Imaging tests (such as a CT scan of your lungs or a chest X-ray) to show lung damage from COPD[12]
- Liver tests (blood tests and imaging tests such as ultrasound) to tell how well your liver is working[12]
Treatment Options
There is no cure for Alpha-1 antitrypsin deficiency[7]. However, treatment can help people with Alpha-1 manage symptoms and slow the progression of the disease. With early diagnosis and the right care, many people with Alpha-1 can prevent serious problems or control symptoms and improve their quality of life[2].
Augmentation Therapy
The only specific treatment for Alpha-1 antitrypsin deficiency is augmentation therapy (also called replacement therapy)[9]. This treatment is only for people with Alpha-1 who have emphysema or severe panniculitis[9].
Augmentation therapy raises the level of alpha-1 antitrypsin in the lungs and blood using AAT protein collected from the plasma (the liquid part of blood) of healthy donors[9]. The therapy is given through weekly infusions directly into the bloodstream through an IV catheter or a port[9].
Five augmentation therapies are approved by the U.S. Food and Drug Administration (FDA): Prolastin-C, Prolastin-C Liquid, Aralast NP, Zemaira, and Glassia[9].
The goal of augmentation therapy is to increase the level of alpha-1 antitrypsin in the lungs to protect them from further damage[9]. The therapy can help slow or stop more damage to the lungs, but it cannot reverse the damage that has already happened or return lung function that has been lost[9]. Studies have shown that augmentation therapy helps preserve lung function and decreases the number and severity of lung infections[13].
Treatments for Lung Disease
Treatment of lung disease may include[2]:
- Bronchodilators: These medicines make breathing easier by relaxing the muscles around the airways. They can be short-acting (lasting 4-6 hours and used as needed) or long-acting (lasting 12 hours or more and used every day)[13]
- Inhaled corticosteroids: These can reduce inflammation of the airways, making it easier to breathe[13]
- Antibiotics: These should be given early for bouts of bronchitis and COPD flare-ups[13]
- Oxygen therapy: Some people may need supplemental oxygen[9]
- Pulmonary rehabilitation: This involves an exercise program, training in managing the condition, nutritional counseling, and psychological counseling[13]
Surgery and Transplantation
In advanced disease, there are surgical options available, such as lung volume reduction surgery and bullectomy[13]. There are also experimental procedures such as valve and coil placement into parts of the airways in an attempt to shrink the damaged areas and improve the function of the less affected areas of the lung[13].
Eventually, patients with very advanced emphysema may require lung transplant surgery[13]. Lung transplantation involves removing a damaged lung and replacing it with a healthy lung from a deceased donor. Lung transplants can significantly improve lung function and quality of life, but involve many risks, including infection and rejection[13].
In those with severe liver disease, liver transplantation may be an option[2].
Vaccinations
Vaccination for influenza, pneumococcus, and hepatitis is recommended to help prevent infections that could worsen lung or liver disease[2]. Yearly flu vaccination and pneumococcal vaccination every 3-5 years is recommended[13].
Living with Alpha-1: Lifestyle Changes
Healthy lifestyle choices, in combination with treatment, can help manage Alpha-1 and prevent the condition from causing other health problems[16]. Certain behavior changes can help prevent or delay lung damage[9].
Avoid Smoking
Not smoking is the best way to reduce the risk of serious complications from Alpha-1[1]. Smoking greatly increases the risk of developing lung disease and speeds up the progression of lung damage in people with Alpha-1[16]. Avoiding smoking is strongly recommended[2].
Secondhand smoke is also an added risk. If someone in your household smokes, ask them to stop or step outside when smoking[17].
Avoid Environmental Pollutants
Pollutants in the workplace and home can be harmful if you have Alpha-1[17]. Steps to protect yourself include:
- Wearing a mask around dust or vapors[17]
- Taking precautions when cleaning, such as ensuring good airflow, avoiding aerosol and spray products, and using natural cleaning products instead of those with harsh chemicals like chlorine and ammonia[16]
- Staying indoors when air pollution levels are too high[17]
- Changing heating and air conditioning filters regularly[17]
Prevent Infections
Common infections like colds or the flu increase the risk of lung infections. People with Alpha-1 should[16]:
- Wash hands regularly
- Get a flu shot every year and other vaccinations as recommended
- Wear a medical-quality or N95 face mask when around other people
- Avoid contact with people who have colds[17]
- Treat infections right away by calling the doctor at the earliest signs of cold or flu[17]
Follow a Healthy Diet
Good nutrition is an important way to maintain health and lung function[17]. A healthy diet improves muscle function, helps preserve the body’s energy and strength, and improves resistance to lung infections[17]. Guidelines include:
- Eating plenty of fruits and vegetables[16]
- Avoiding processed foods[16]
- Choosing healthy proteins such as beans and nuts[16]
- Getting plenty of vitamin D, which supports overall lung health[16]
- Maintaining adequate levels of phosphorus by eating dairy, lean meats, fish, beans, peas, whole grain cereals, and nuts[17]
- Avoiding alcohol[16]
- Maintaining a healthy weight by balancing energy needs and food intake[17]
Exercise Regularly
Routine exercise can help improve mental outlook, stamina, and physical well-being[17]. Exercise improves overall health and lung health in particular. However, Alpha-1 can affect breathing and the ability to exercise safely. It’s important to talk to your doctor before starting regular exercise. They may run tests to measure heart and lung function to help determine how much exercise is safe[16]. Many people find that simple stretching exercises, walking, or bicycling improves exercise tolerance[17].
Manage Stress
Managing stress may help you feel better and avoid adverse effects on health[17]. Stress management may offer benefits such as improved breathing, reduced shortness of breath, and relief of anxiety. Relaxation techniques include[16]:
- Breathing exercises
- Yoga
- Meditation
- Muscle relaxation[17]
Seek Emotional Support
Coping with Alpha-1 can be challenging and may lead to anxiety or depression, which affects quality of life. Support groups exist to help people with Alpha-1 cope with their diagnosis[16].
Outlook and Life Expectancy
Alpha-1 is not necessarily a terminal illness[1]. Many people with Alpha-1, especially if they don’t smoke, can live a normal lifespan[1]. Some people who have never smoked may live a typical lifespan, though they may still develop lung disease, liver disease, or both[2].
Life expectancy among those who smoke is approximately 50 years, while among those who do not smoke it is almost normal[8]. About 75% of people with two abnormal genes will eventually develop lung function issues[1].
With early diagnosis and appropriate treatment, many people with Alpha-1 can prevent serious problems or control symptoms and improve their quality of life[2]. The key is to avoid smoking, take prescribed treatments, follow a healthy lifestyle, and work closely with healthcare providers to manage the condition[9].
