What is Alpha-1 Antitrypsin Deficiency?

Alpha-1 antitrypsin (AAT) deficiency is a disorder that’s passed down through families, and it often goes unnoticed in medical check-ups. This condition causes a decrease in the production of the alpha-1 antitrypsin protein. This protein is important because it helps protect the body from an enzyme called neutrophil elastase. This enzyme is produced by white blood cells when they’re fighting an infection. Because of the deficiency in this protein, there’s less active AAT in the blood and lungs. Plus, abnormal levels of AAT can build up in the liver, causing liver disease.

The root cause of this deficiency and the presence of abnormal AAT protein is changes or mutations in a certain gene called the SERPINA1 gene. Lower levels of active AAT can result in damage to the small air sacs in the lungs (called alveoli) by neutrophil elastase, leading to lung disease. Additionally, abnormal AAT can collect in the liver, causing harm to this organ.

People with AAT deficiency usually start to show signs of lung disease, like emphysema and bronchiectasis, between the ages of 20 and 50. Research has shown that smoking cigarettes significantly worsens the decline in lung function. This article will cover the causes, frequency, signs and symptoms, diagnosis, and treatment for AAT deficiency.

What Causes Alpha-1 Antitrypsin Deficiency?

AAT deficiency is a condition that you can inherit from both of your parents. It’s caused by abnormalities in a specific gene, SERPINA1, that’s on chromosome 14. This gene is responsible for making a protein called Alpha-1 Antitrypsin (AAT).

There are over 150 different versions, or “alleles”, of this gene, and each one is known by a letter. The most common version of this gene is the “M” allele, which is the normal one. Most people have two copies of the M allele (MM) in each cell. When there are variations in this gene, it leads to lower levels of AAT.

For example, the S allele leads to slightly low levels of AAT, while the Z allele causes significantly low levels of AAT. If you have two copies of the Z allele (ZZ) in each cell, you’re likely to have AAT deficiency. If you have an SZ combination, you’re more likely to develop lung diseases such as emphysema, especially if you smoke.

Around the world, about 161 million people carry one copy of the S or Z allele and one copy of the M allele in each cell (MS or MZ). If you have an MS or SS combination, you usually produce enough AAT to protect your lungs. However, if you have an MZ combination, you have a slightly increased risk of developing lung or liver problems.

AAT “phenotypes”, or characteristics, are based on the movement of the proteins produced by the different versions of the AAT gene. Genotyping, the process of identifying specific versions of genes, is done by looking at specific alleles in the DNA.

Based on this, AAT can be categorized into four main groups:

1. Normal: This is associated with normal levels of AAT and its proper functioning. The group of normal versions is known as “M”, and the normal AAT level genotype is “MM”.

2. Deficient: This is associated with AAT levels in your blood plasma below 35% of the normal level. The most common deficient version associated with emphysema is the Z allele, which is present in about 2% to 3% of the Caucasian population in the US.

3. Null: This results in no detectable AAT protein in the blood plasma. People with the null genotype are less common and are at a higher risk for severe lung disease, while liver disease is typically not associated with null alleles.

4. Dysfunctional: This is characterized by producing a normal amount of AAT protein, but the protein doesn’t function properly. This dysfunction can be due to either a conversion defect from an elastase inhibitor to a thrombin inhibitor, or the presence of the PI*F variant.

Risk Factors and Frequency for Alpha-1 Antitrypsin Deficiency

AAT deficiency is a global health issue, but the extent of its impact varies from one population to another. It affects approximately 1 in every 2,000 to 6,000 people, increasing their risk of liver disease and early development of emphysema. This condition is more common in people of European origin, while it is less frequent among Asians and other races.

Even though AAT deficiency is considered rare, it is thought that there are between 80,000 to 100,000 individuals in the United States alone who suffer from a severe lack of AAT. This suggests that the condition might be more common than recognized. Globally, it is estimated that over 3 million individuals have severe AAT deficiency related to their inherited genes.

Signs and Symptoms of Alpha-1 Antitrypsin Deficiency

AAT deficiency is a condition that primarily impacts three organs: the lungs, the liver, and sometimes the skin, each leading to different symptoms.

When the lungs are affected by AAT deficiency, patients might have diseases like emphysema, which shares many symptoms with COPD, a lung disease often seen in smokers. The two unique characteristics of AAT-related emphysema include the early age at which symptoms start and a distinct form of emphysema. According to research, people with AAT-related emphysema usually have symptoms at a younger age and lower than normal lung function scores. Shortness of breath is the most common symptom, but many patients also have a chronic cough, produce phlegm, and wheeze regularly or when they have an upper respiratory infection. Spontaneous secondary pneumothorax, or collapsed lung, may be either the initial symptom or a subsequent complication of the disease. Bronchiectasis, a condition where the large airways in the lungs are damaged, has also been associated with severe AAT deficiency.

The liver can also be affected by AAT deficiency, leading to conditions such as adult-onset chronic hepatitis, cirrhosis, or liver cancer in at-risk patients.

Sometimes the skin may be involved, leading to conditions like necrotizing panniculitis or red lumps or patches on the thigh or buttocks. AAT deficiency can also be connected to other health issues like systemic vasculitis, intracranial and peripheral aneurysms, psoriasis, hives, swelling, potential ties with inflammatory bowel disease, fibromuscular dysplasia, peripheral neuropathy, and glomerulonephritis, a type of kidney disease.

Testing for Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin (AAT) deficiency is an underdiagnosed condition due to limited access to healthcare and treatment. It’s crucial to screen for this deficiency using various methods, especially among individuals who have symptoms that could point to it. People who have related health conditions such as Chronic Obstructive Pulmonary Disease (COPD), unexplained liver disease, asthma, and certain types of vasculitis – an inflammation of the blood vessels – are especially at risk. Other conditions that may warrant testing for AAT deficiency include Panniculitis, a skin disorder, and Bronchiectasis, a lung condition.

A variety of diagnostic procedures can help detect AAT deficiency. Your doctor will likely start by taking your medical history and performing a physical examination. They might also order liver-function tests, complete pulmonary function tests (PFT) and possibly a chest X-ray. PFTs are used to evaluate the presence and level of lung disease while a chest X-ray can determine the pattern and extent of any resulting emphysema, a type of lung damage. If your breathing is affected, an additional six-minute walk test could be performed to measure the severity of the condition.

If there’s a chance that AAT deficiency is present, a blood test may be ordered to measure the level of AAT in your bloodstream. Genotyping, a method of analyzing your genetic information, might also be conducted to identify specific genetic mutations associated with the condition. In some cases, gene sequencing might be used to decipher the genetic code in search of unidentified variants.

Patients who have AAT deficiency but are currently symptom-free might still need to undergo regular lung function tests. If symptoms appear or lung function decreases, your doctor might consider initiating augmentation therapy, a treatment used to increase AAT levels in your bloodstream.

For patients at risk of liver disease, annual tests are usually conducted to measure liver enzyme and bilirubin levels. Bilirubin is a waste product that the liver usually breaks down and removes from the body. Some doctors might also recommend testing your platelet levels or conducting an abdominal ultrasound check for any signs of liver cirrhosis, a condition which causes scar tissue to replace healthy liver cells.

It’s important to remember that the symptoms of AAT deficiency can vary significantly among individuals. Environmental factors such as smoking or exposure to dust and kerosene can play a significant role in the severity or appearance of symptoms.

Treatment Options for Alpha-1 Antitrypsin Deficiency

For patients suspected or diagnosed with AAT deficiency, which is a condition that could lead to lung and liver diseases, it’s very important to quit smoking. If you have a severe form of this condition, it’s recommended to have regular check-ups, usually every 6 to 12 months. These check-ups include tests to assess how well your lungs are working, how far you can walk in 6 minutes, as well as evaluations of your overall health and quality of life.

Common treatments include inhalers and medications, which are often also used to manage Chronic Obstructive Pulmonary Disease (COPD). If your resting oxygen levels fall below a certain point, you may need oxygen therapy at home. You should also receive routine vaccination against respiratory infections, like the flu and pneumonia. Rehabilitation exercises for the lungs and nutritional support are also an important part of treatment.

The only specific therapy designed for AAT deficiency involves an infusion of a protein called alpha-1 antitrypsin, which can help raise the levels of AAT in your body. This treatment has been shown to slow down the loss of lung density, however, it hasn’t been proven to improve lung function or quality of life.

Different medical organizations have different recommendations regarding this therapy with alpha-1 antitrypsin. Some suggest using it weekly for certain individuals, while others recommend it for patients who have quit smoking, and for those patients whose disease isn’t adequately managed by other treatments. However, not all patients are suitable for this therapy. It’s not recommended for smokers, patients with certain genetic profiles, or those with AAT levels above a specific limit.

Side effects from the alpha-1 antitrypsin infusion are rare but can include mild fever, flu-like symptoms, and a few rare but serious conditions. Before starting this therapy, it is also recommended to check for IgA deficiency, a condition that could lead to severe allergic reactions to the infusion.

For severe AAT deficiency, lung transplantation can improve both the quality of life and survival rates. However, certain other therapies are not recommended due to a lack of evidence showing their benefits.

For patients with liver-related issues due to AAT deficiency, regular check-ups for liver function are essential. However, alpha-1 antitrypsin infusion therapy is not recommended for AAT-related liver diseases. If you also have cirrhosis (scarring of the liver), it’s important to have regular screenings for liver cancer. In severe cases, liver transplantation could be the right course of treatment.

In cases of AAT (Alpha-1 Antitrypsin) deficiency affecting the lungs, doctors might consider other conditions that have similar symptoms. These include:

  • Emphysema – lung condition that causes shortness of breath
  • Chronic bronchitis – long-term inflammation of the bronchial tubes in your lungs
  • Bronchiectasis – a disease where the bronchial tubes in your lungs are permanently damaged, widened, and thickened

When AAT deficiency affects the liver, these potential diagnoses might be considered:

  • Chronic viral hepatitis – long-lasting liver inflammation due to viral infection
  • Hereditary hemochromatosis – a genetic disorder that causes your body to absorb too much iron from the food you consume
  • Wilson’s disease – a rare inherited disorder causing copper to accumulate in vital organs
  • Non-alcoholic steatohepatitis – a type of fatty liver disease, where fat builds up in the liver and causes inflammation or damage
  • Primary biliary cirrhosis – a chronic disease that slowly destroys the bile ducts in the liver

What to expect with Alpha-1 Antitrypsin Deficiency

During the first 30 years of life, people with Alpha-1 Antitrypsin (AAT) deficiency mainly see negative impacts on their liver health while their lungs are less affected. But when people get older, it’s less certain what will happen to those suffering from severe AAT deficiency. This uncertainty stems from the fact that different studies draw upon different groups of people, leading to varied survival estimates.

For people with AAT deficiency who don’t smoke and show no symptoms, they may have a life expectancy similar to those without the condition. However, these findings will require more long-term research for confirmation. The Forced Expiratory Volume in one second (FEV1), which measures how much air a person can force out of their lungs in one second, plays a crucial role in predicting survival rates in people with AAT deficiency. As the FEV1 reduces to less than 35% of the expected value, the risk of death increases. Other factors that help predict the severity of the condition include a reduction in lung density, as judged by a chest CT scan.

The outlook for those with AAT deficiency varies and is influenced by factors such as disease severity, complications, and how a person responds to treatment. Lung diseases associated with AAT deficiency can continuously and irreversibly damage the lungs, leading to conditions like Chronic Obstructive Pulmonary Disease (COPD), emphysema, and breathing problems.

On the other hand, for individuals dealing with liver disease due to AAT deficiency, the outlook can also vary. In some cases, liver disease may develop into cirrhosis, a condition that causes liver scarring and prevents the liver from working properly, which may lead to serious complications like liver failure or liver cancer. As such, the forecast for these patients can be very serious.

Possible Complications When Diagnosed with Alpha-1 Antitrypsin Deficiency

The issues that can arise from alpha-1 antitrypsin deficiency are:

  • Asthma
  • Emphysema
  • Chronic Bronchitis
  • Chronic Liver Disease

Preventing Alpha-1 Antitrypsin Deficiency

If you have alpha-1 antitrypsin deficiency, it’s important to stop smoking and avoid being around occupational dust, such as from construction sites or certain factories. It’s also recommended to get yearly flu and pneumonia shots. Doing all these can help slow down the worsening of lung disease and lower the chance of getting lung infections and related health problems.

To prevent further complications related to liver disease, you should restrict your alcohol intake or if possible, quit drinking alcohol entirely. Receiving hepatitis A and B vaccinations is also suggested to protect your liver from these diseases.

It’s advised that close family members of individuals with alpha-1 antitrypsin deficiency have genetic counseling and testing. This is because they have a higher chance of having the same genetic risk factors related to this condition.

Frequently asked questions

Alpha-1 antitrypsin (AAT) deficiency is a genetic disorder that causes a decrease in the production of the alpha-1 antitrypsin protein. This protein is important for protecting the body from an enzyme called neutrophil elastase. The deficiency in this protein can lead to lung disease and liver disease.

It affects approximately 1 in every 2,000 to 6,000 people, increasing their risk of liver disease and early development of emphysema.

Signs and symptoms of Alpha-1 Antitrypsin Deficiency (AAT deficiency) can vary depending on which organs are affected. The primary organs impacted by AAT deficiency are the lungs, liver, and sometimes the skin. Here are the signs and symptoms associated with each: 1. Lungs: - Early onset of symptoms, usually at a younger age than typical lung diseases - Lower than normal lung function scores - Shortness of breath, which is the most common symptom - Chronic cough - Production of phlegm - Regular wheezing or wheezing during upper respiratory infections - Increased risk of spontaneous secondary pneumothorax (collapsed lung) - Association with bronchiectasis, a condition where the large airways in the lungs are damaged 2. Liver: - Adult-onset chronic hepatitis - Cirrhosis - Liver cancer in at-risk patients 3. Skin: - Necrotizing panniculitis, which is the inflammation of fat cells under the skin leading to red lumps or patches on the thigh or buttocks In addition to these specific organ-related symptoms, AAT deficiency can also be associated with other health issues, including: - Systemic vasculitis - Intracranial and peripheral aneurysms - Psoriasis - Hives - Swelling - Potential ties with inflammatory bowel disease - Fibromuscular dysplasia - Peripheral neuropathy - Glomerulonephritis, a type of kidney disease It is important to note that not all individuals with AAT deficiency will experience all of these symptoms, and the severity can vary from person to person. If you suspect you may have AAT deficiency, it is recommended to consult with a healthcare professional for proper diagnosis and management.

Alpha-1 Antitrypsin Deficiency is a condition that you can inherit from both of your parents.

Emphysema, Chronic bronchitis, Bronchiectasis, Chronic viral hepatitis, Hereditary hemochromatosis, Wilson's disease, Non-alcoholic steatohepatitis, Primary biliary cirrhosis.

The types of tests that are needed for Alpha-1 Antitrypsin Deficiency include: - Medical history and physical examination - Liver-function tests - Complete pulmonary function tests (PFT) - Chest X-ray - Six-minute walk test (if breathing is affected) - Blood test to measure AAT levels in the bloodstream - Genotyping to identify specific genetic mutations - Gene sequencing to search for unidentified variants - Regular lung function tests for symptom-free patients - Annual tests for liver enzyme and bilirubin levels for patients at risk of liver disease - Platelet level tests - Abdominal ultrasound check for signs of liver cirrhosis It is important to note that the specific tests ordered may vary depending on the individual's symptoms and risk factors.

Alpha-1 Antitrypsin Deficiency is treated through various methods. Common treatments include inhalers and medications, routine vaccination against respiratory infections, rehabilitation exercises for the lungs, and nutritional support. In severe cases, an infusion of a protein called alpha-1 antitrypsin can be administered to raise the levels of AAT in the body, which has been shown to slow down the loss of lung density. However, this treatment has not been proven to improve lung function or quality of life. The use of alpha-1 antitrypsin therapy is recommended for certain individuals, such as those who have quit smoking and whose disease is not adequately managed by other treatments. However, it is not suitable for all patients, particularly smokers, patients with certain genetic profiles, or those with AAT levels above a specific limit.

The side effects when treating Alpha-1 Antitrypsin Deficiency with an infusion of alpha-1 antitrypsin can include mild fever, flu-like symptoms, and a few rare but serious conditions. It is also recommended to check for IgA deficiency before starting this therapy, as it could lead to severe allergic reactions to the infusion.

The prognosis for Alpha-1 Antitrypsin Deficiency varies depending on factors such as disease severity, complications, and response to treatment. Lung diseases associated with AAT deficiency can cause irreversible damage to the lungs, leading to conditions like COPD, emphysema, and breathing problems. Liver disease due to AAT deficiency can also have serious complications, such as cirrhosis, liver failure, or liver cancer. The outlook for individuals with AAT deficiency can be very serious.

A pulmonologist or a hepatologist.

Join our newsletter

Stay up to date with the latest news and promotions!

"*" indicates required fields

This field is for validation purposes and should be left unchanged.