Overview

Alpha-1 Antitrypsin Deficiency (AATD) is a genetic disorder caused by a mutation in the SERPINA1 gene, which provides instructions for making the alpha-1 antitrypsin protein. This causes the protein to be improperly folded and to accumulate in the liver cells, where it cannot be secreted into the bloodstream. This can lead to liver damage and inflammation, and in some cases also result in a decrease of functional alpha-1 antitrypsin protein in the blood, leading to lung damage. Diagnosis of AATD is typically made through a combination of blood tests and medical history. Treatment for AATD aims to slow the progression of lung and liver damage, alleviate symptoms, and improve the patient's quality of life.

 

What is Alpha-1 Antitrypsin deficiency?

Alpha-1 antitrypsin deficiency is a genetic disorder that can lead to lung and liver damage. It is caused by a deficiency of the alpha-1 antitrypsin protein, which is responsible for protecting the lungs from the effects of certain enzymes. This can lead to lung problems such as emphysema, as well as liver problems such as cirrhosis. The disorder is inherited in an autosomal recessive manner, which means that an individual must inherit two copies of the defective gene (one from each parent) in order to develop the disorder. Symptoms can include shortness of breath, wheezing, and chronic cough.

Who does Alpha-1 affect?

Alpha-1 antitrypsin deficiency affects people of all races and ethnicities, but it is more common in people of Northern European descent. It is estimated that about one in every 1,500 to 3,500 individuals of Northern European descent have the disorder. However, it is also found in other populations, including African Americans, Hispanic Americans, and Asian Americans. The disorder affects both men and women equally.

Individuals with Alpha-1 antitrypsin deficiency are at increased risk of developing lung disease, particularly emphysema, which is a type of chronic obstructive pulmonary disease (COPD). The lung problems caused by the disorder usually begin to develop in adulthood, often in individuals between the ages of 20 and 50.

Liver disease is less common in people with Alpha-1 antitrypsin deficiency, but it can still occur, usually in people over the age of 40.

 

How common is Alpha-1?

Alpha-1 antitrypsin deficiency is a relatively rare genetic disorder, but it is one of the most common genetic causes of COPD (Chronic Obstructive Pulmonary Disease) worldwide. The prevalence of Alpha-1 antitrypsin deficiency varies depending on the population and can range from 1 in 1,500 to 1 in 4,000 individuals. It is estimated that there are around 100,000 people with Alpha-1 antitrypsin deficiency in the United States and around 3-5 million worldwide.

It is more common in individuals of Northern European descent with an estimated prevalence of 1 in 2,500 to 1 in 3,500 individuals. However, it is also found in other populations, including African Americans, Hispanic Americans, and Asian Americans.

It is an autosomal recessive disorder, which means that an individual must inherit two copies of the defective gene (one from each parent) in order to develop the disorder. The disorder affects both men and women equally.

 

What causes Alpha-1 antitrypsin deficiency? 

Alpha-1 antitrypsin deficiency is caused by a genetic mutation in the SERPINA1 gene, which provides instructions for making the alpha-1 antitrypsin protein. The SERPINA1 gene is located on chromosome 14 and it is inherited in an autosomal recessive manner, which means that an individual must inherit two copies of the defective gene (one from each parent) in order to develop the disorder.

The most common mutation that leads to Alpha-1 antitrypsin deficiency is a change in the amino acid sequence of the alpha-1 antitrypsin protein, known as the PiZ allele, which causes the protein to be improperly folded and to accumulate in the liver cells, where it cannot be secreted into the blood stream.

This accumulation of abnormal alpha-1 antitrypsin protein in the liver cells can lead to liver damage and inflammation, and in some cases also result in a decrease of functional alpha-1 antitrypsin protein in the blood. This decrease in functional protein can lead to lung damage by allowing proteases to attack the lung tissue.

It's important to note that not everyone who inherits two copies of the defective gene will develop lung or liver problems, and the severity of symptoms can vary widely, depending on the specific mutation and other factors such as environmental exposure or lifestyle.

 

How does Alpha-1 deficiency affect my lungs and liver?

Alpha-1 antitrypsin deficiency affects the lungs and liver by causing a deficiency of the alpha-1 antitrypsin protein, which is responsible for protecting the lungs and liver from the effects of certain enzymes.

In the lungs, the deficiency of alpha-1 antitrypsin protein can lead to the destruction of lung tissue, particularly in the small air sacs (alveoli) of the lungs. This can cause emphysema, a type of chronic obstructive pulmonary disease (COPD) characterized by difficulty breathing, chronic cough and wheezing. The lung damage caused by Alpha-1 deficiency is usually progressive, meaning that it tends to get worse over time.

In the liver, the deficiency of alpha-1 antitrypsin protein can lead to the accumulation of abnormal forms of the protein in the liver cells, which can cause liver damage and inflammation. This can lead to cirrhosis, a condition in which the liver is replaced by scar tissue and is unable to function properly. The liver damage caused by Alpha-1 deficiency is usually slow progressing and may not cause symptoms until later in life.

It's important to note that not all individuals with Alpha-1 antitrypsin deficiency will develop lung or liver problems, and the severity of symptoms can vary widely. Early diagnosis and treatment can help slow the progression of lung and liver damage.

 

What are the symptoms of Alpha-1 antitrypsin deficiency?

The symptoms of Alpha-1 antitrypsin deficiency can vary depending on the individual and the severity of the deficiency. Some people with the disorder may not have any symptoms, while others may develop serious lung and liver problems.

 

Symptoms of lung problems caused by Alpha-1 antitrypsin deficiency can include:

• Shortness of breath, especially with physical activity
• Wheezing
• Chronic cough
• Chest tightness
• Recurrent respiratory infections
• Fatigue
• Rapid breathing

 

Symptoms of liver problems caused by Alpha-1 antitrypsin deficiency can include:

• Jaundice (yellowing of the skin and whites of the eyes)
• Fatigue
• Loss of appetite
• Abdominal pain
• Nausea and vomiting
• Swelling in the legs and abdomen
• Bruising easily

 

It's important to note that these symptoms can also be caused by other health conditions and are not specific to Alpha-1 antitrypsin deficiency. If you have a family history of Alpha-1 antitrypsin deficiency, have symptoms of lung or liver problems, or are concerned about your risk for the disorder, it is important to talk to your doctor.

How is Alpha-1 antitrypsin deficiency diagnosed?

Alpha-1 antitrypsin deficiency is typically diagnosed through a combination of blood tests and medical history.

A blood test is used to measure the level of alpha-1 antitrypsin in the blood. Individuals with the disorder will typically have low levels of alpha-1 antitrypsin protein. However, it's important to note that not everyone with low levels of alpha-1 antitrypsin protein has the disorder, and not everyone with the disorder will have low levels of the protein.

If the blood test shows low levels of alpha-1 antitrypsin protein, genetic testing can be used to determine if an individual has two copies of the defective gene that causes the disorder. Genetic testing can also be used to confirm a diagnosis in individuals who have a family history of the disorder but do not have symptoms.

A chest X-ray or CT scan may also be done to check for any signs of lung damage that may be caused by Alpha-1 antitrypsin deficiency. A breathing test, such as spirometry, may also be performed to measure lung function.

A liver function test, an ultrasound, or a liver biopsy may be done to check for any signs of liver damage that may be caused by Alpha-1 antitrypsin deficiency.

It's important to note that Alpha-1 antitrypsin deficiency can be difficult to diagnose in the early stages, because symptoms may be mild or similar to those of other respiratory or liver conditions. In some cases, a diagnosis may not be made until the individual has already developed serious lung or liver problems.

 

How is Alpha-1 treated?

The treatment of Alpha-1 antitrypsin deficiency aims to slow the progression of lung and liver damage, alleviate symptoms, and improve the patient's quality of life.

 

Treatment options for lung problems caused by Alpha-1 antitrypsin deficiency include:

• Augmentation therapy: This involves providing the patient with additional alpha-1 antitrypsin protein, which can help to protect the lungs from further damage. The protein is given as an injection or an intravenous infusion, usually once or twice a week.
• Medications: bronchodilators, inhaled corticosteroids and antibiotics can be prescribed to help alleviate symptoms such as shortness of breath, wheezing and chronic cough.
• Oxygen therapy: may be necessary if the patient has low levels of oxygen in their blood.
• Lifestyle changes: Quitting smoking and avoiding exposure to lung irritants can help slow the progression of lung damage.

 

Treatment options for liver problems caused by Alpha-1 antitrypsin deficiency include:

• Medications: ursodeoxycholic acid (UDCA) can be used to reduce inflammation and prevent the formation of liver scar tissue.
• Lifestyle changes: Avoiding alcohol, maintaining a healthy diet and maintaining a healthy weight can help slow the progression of liver damage.

Surgery, such as a lung transplant or a liver transplant, may be necessary in some cases, particularly if the patient has advanced lung or liver disease.

It's important to note that treatment plans will vary depending on the individual and the severity of their condition. Regular follow-up appointments with a healthcare provider are important to monitor the progression of the disease and to adjust the treatment plan as needed.

What can’t I eat/drink with Alpha-1? 

There is no specific diet recommended for individuals with Alpha-1 antitrypsin deficiency. However, if you have been diagnosed with liver problems caused by the disorder, there are a few dietary considerations that you should keep in mind to help protect your liver and slow the progression of liver damage.

• Alcohol: It's recommended that individuals with liver problems caused by Alpha-1 antitrypsin deficiency avoid alcohol completely, as alcohol can cause further damage to the liver.
• Salt: High-salt diets can lead to water retention, which can put more stress on the liver. It's recommended that individuals with liver problems caused by Alpha-1 antitrypsin deficiency avoid excessive salt intake.
• Sugar: High sugar intake, especially in the form of added sugars found in processed foods and drinks, can contribute to fatty liver disease, a condition that can lead to liver damage. It's recommended that individuals with liver problems caused by Alpha-1 antitrypsin deficiency avoid high sugar intake.
• Foods that are high in saturated fats and cholesterol, such as butter, cheese, red meat, fried foods and processed foods, should be avoided or consumed in moderation. Eating a well-balanced diet that is high in fruits, vegetables, and lean proteins can help to protect your liver and support overall health.

If you are unsure about what foods or drinks to avoid, it's best to consult with a dietitian or a healthcare provider. They can provide you with personalized advice on how to maintain a healthy diet while managing your Alpha-1 antitrypsin deficiency.

How can I prevent Alpha-1?

Alpha-1 antitrypsin deficiency is a genetic disorder, and there is no known way to prevent the disorder itself. However, if you are at risk of developing the disorder or have already been diagnosed with it, there are steps you can take to help slow the progression of lung and liver damage, and improve your overall health.

• Quit smoking: Smoking is a major risk factor for lung damage and can significantly increase the progression of lung disease in individuals with Alpha-1 antitrypsin deficiency. Quitting smoking can help to slow the progression of lung damage, improve lung function and reduce the risk of respiratory infections.
• Avoid lung irritants: Exposure to environmental pollutants, such as pollution, chemical fumes, and dust, can irritate the lungs and accelerate lung damage. Avoiding exposure to these irritants can help to slow the progression of lung damage.
• Maintain a healthy diet: Eating a well-balanced diet that is high in fruits, vegetables, and lean proteins can help to support overall health, and may help to slow the progression of liver damage.
• Exercise regularly: Regular exercise can help to improve lung function and reduce the risk of respiratory infections.
• Get regular check-ups: Regular follow-up appointments with a healthcare provider are important to monitor the progression of the disease and to adjust the treatment plan as needed.

It's also important to note that if you have a family history of Alpha-1 antitrypsin deficiency, it's important to talk to your doctor about your risk of developing the disorder. Genetic testing can be done to determine if you have the defective gene, and if you test positive, you may be eligible for early diagnosis and treatment that can help slow the progression of lung and liver damage.

 

What can I expect if I have Alpha-1?

If you have been diagnosed with Alpha-1 antitrypsin deficiency, you can expect to work closely with a healthcare team that will help you manage your condition and keep it under control.

The course of the disease and the symptoms can vary widely between individuals with Alpha-1. Some people may have only mild symptoms and a slow progression of the disease, while others may experience a more severe form of the disease and have more advanced symptoms.

You can expect to have regular check-ups with your healthcare provider to monitor your condition and adjust your treatment plan as needed. This may include blood tests, breathing tests, chest X-rays or CT scans, and ultrasound or liver biopsy.

You will also be advised to avoid smoking, exposure to lung irritants, and excessive alcohol consumption. Depending on the severity of your lung problems, you may be prescribed medications such as bronchodilators and inhaled corticosteroids, antibiotics, and oxygen therapy. You may also be prescribed augmentation therapy, which involves providing the patient with additional alpha-1 antitrypsin protein to help protect the lungs from further damage.

If you have liver problems, you may be prescribed medication such as ursodeoxycholic acid (UDCA) to reduce inflammation and prevent the formation of liver scar tissue.

In some cases, surgery such as lung or liver transplant may be necessary.

 

What are the complications of Alpha-1?

 

Alpha-1 antitrypsin deficiency can lead to a number of complications, both in the lungs and in the liver.

Lung complications:

• Emphysema: a condition characterized by the destruction of the small air sacs (alveoli) in the lungs, leading to difficulty breathing and chronic cough.
• Chronic bronchitis: inflammation of the airways, leading to chronic cough and excess mucus production.
• Respiratory infections: individuals with Alpha-1 antitrypsin deficiency may be more prone to respiratory infections such as pneumonia and bronchitis.
• Pulmonary hypertension: High blood pressure in the lung's blood vessels, which can make it harder for the heart to pump blood through the lungs.

 

Liver complications:

• Cirrhosis: a condition in which the liver is replaced by scar tissue and is unable to function properly.
• Liver failure: the inability of the liver to function properly and perform its many essential tasks.
• Liver cancer: Individuals with cirrhosis caused by Alpha-1 antitrypsin deficiency have a higher risk of developing liver cancer.

 

It's important to note that not all individuals with Alpha-1 antitrypsin deficiency will develop these complications. With proper management and treatment, many individuals with Alpha-1 antitrypsin deficiency are able to lead normal lives and maintain good quality of life. However, early diagnosis and treatment can help slow the progression of lung and liver damage, and reduce the risk of complications.

 

What is the life expectancy of someone with alpha-1 antitrypsin deficiency?

The life expectancy of an individual with Alpha-1 antitrypsin deficiency can vary depending on the severity of the disorder, the presence of lung and liver problems, and the effectiveness of treatment.

Individuals with Alpha-1 antitrypsin deficiency who have mild symptoms and a slow progression of the disease may have a normal life expectancy. However, in some cases, the disorder can lead to serious lung and liver problems that can significantly shorten life expectancy.

Smoking is a major risk factor for lung damage in individuals with Alpha-1 antitrypsin deficiency, and quitting smoking can help to slow the progression of lung damage, improve lung function and reduce the risk of respiratory infections. Avoiding exposure to lung irritants, maintaining a healthy diet, regular exercise and getting regular check-ups with a healthcare provider can also help to slow the progression of the disease and improve the quality of life.

In some cases, surgery such as lung or liver transplant may be necessary, especially if the patient has advanced lung or liver disease and these procedures can improve the patient's life expectancy.

 

When should you consult your doctor if you have Alpha-1 symptoms?

If you have symptoms of Alpha-1 antitrypsin deficiency, such as shortness of breath, chronic cough, wheezing, chest tightness, recurrent respiratory infections, fatigue, rapid breathing, jaundice, loss of appetite, abdominal pain, nausea and vomiting, swelling in the legs and abdomen, and bruising easily, it is important to see your healthcare provider as soon as possible.

If you have a family history of Alpha-1 antitrypsin deficiency or are concerned about your risk for the disorder, it is important to talk to your doctor. They can help determine if you have symptoms of the disorder and will refer you to a specialist if necessary.

Early diagnosis and treatment of Alpha-1 antitrypsin deficiency can help slow the progression of lung and liver damage, alleviate symptoms, and improve the patient's quality of life. Your healthcare provider will work with you to develop an individualized treatment plan that includes medications, lifestyle changes, and close monitoring of your condition.

 

Conclusion 

Alpha-1 antitrypsin deficiency is a genetic disorder that affects the lungs and liver. It is caused by a deficiency of the alpha-1 antitrypsin protein, which is responsible for protecting the lungs from the effects of certain enzymes. This can lead to lung problems such as emphysema and chronic bronchitis, as well as liver problems such as cirrhosis. The disorder is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the defective gene (one from each parent) in order to develop the disorder. 

Symptoms can include shortness of breath, wheezing, and chronic cough. Treatment options include augmentation therapy, which involves providing the patient with additional alpha-1 antitrypsin protein, and lifestyle changes such as quitting smoking and avoiding exposure to lung irritants. In some cases, lung transplantation may be necessary.