Alpha-1 Antitrypsin Deficiency: Symptoms, Causes, and Treatment

An Overview Detail on Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin refers to a genetic condition that can result in lung disorders and liver disorders. This condition has symptoms that are different from one person to another and the age of onset of these symptoms also differ.

Individuals with alpha-1 antitrypsin deficiency start experiencing the first symptoms of lung disease between the ages of twenty-five and fifty. The first signs of the disease include difficulty in breathing after lightly exerting yourself, exercise tolerance, and whistling. Other symptoms that may be present include unexplained weight loss, frequent episodes of respiratory infections, and always feeling tired. People who suffer from this condition experience a significant level of emphysema, a condition that occurs due to the deterioration of the alveoli in the lungs. Signs and symptoms of emphysema include failure to breathe as required, persistent coughing, and a chest that has a barreled shape. Smoking or exposure to tobacco smoke worsens the rate at which emphysema develops and the extent of lung injury.

In rare circumstances, roughly less than 10 percent of infants that have alpha-1 antitrypsin deficiency develop liver disease that results in the skin and the whites of the eyes appearing to have a yellow hue (jaundice). It is significant to note that 15% of adults with alpha-1 antitrypsin deficiency cause liver damage cirrhosis because scar tissues are formed in the liver. The presence of ascites and yellowness of the skin features cirrhosis symptoms. Patients with alpha-1 antitrypsin deficiency also have an increased risk of liver cancer – hepatocellular carcinoma.

Although panniculitis is quite rare, it is one of the cutaneous manifestations seen in patients with alpha-1 antitrypsin deficiency. Panniculitis can present with mild or extensive presentations and may occur in patients of any age.

Causes of Alpha-1 Antitrypsin Deficiency

Mutations in the SERPINA1 gene lead to the development of Alpha-1 antitrypsin deficiency which is also referred to as variants. This gene is involved in the production of the alpha-1 antitrypsin protein, an enzyme that helps the body combat the damaging effects of a certain enzyme known as neutrophil elastase. Neutrophil elastase is a protein produced by white blood cells to combat infection; however, it readily targets normal tissues most specifically the lungs if not inhibited by alpha-1 antitrypsin.

Mutations in the SERPINA1 gene are associated with poor production of alpha-1 antitrypsin or the production of a protein that cannot suppress neutrophil elastase. If there is not sufficient functional alpha-1 antitrypsin in the body, neutrophil elastase leads to the destruction of alveoli and lung disorders. Pathological forms of alpha-1 antitrypsin can also be deposited in the liver and lead to this organ’s dysfunction.

The progression of alpha-1 antitrypsin deficiency has been considered to depend on certain environmental factors, including tobacco smoke, chemicals, and dust.

People with an abnormal Alpha-1 gene can therefore be expected to pass down the genetic mutation to their offspring. If both parents are carriers of the gene, their children have 1 in 4 chances of inheriting two flawed genes the rest 2 out of 4 children will be recessive gene carriers that is they shall have one perfect gene and one flawed gene. Since both genes are concerned with how you produce AAT and not with one gene overpowering the other, thus, Alpha-1 antitrypsin deficiency has a codominant trait.

Symptoms of Alpha-1 Antitrypsin Deficiency

Lung conditions associated with Alpha-1 deficiency exhibit symptoms akin to those of chronic obstructive pulmonary disease (COPD). These respiratory symptoms typically manifest between the ages of 30 and 50 and may include:

• Difficulty in breathing (dyspnea), particularly during physical activity.
• A wheezing sound during respiration.
• A persistent cough, frequently accompanied by mucus.
• Severe fatigue.
• Recurrent respiratory infections.

Approximately 10% of infants and 15% of adults diagnosed with Alpha-1 develop liver disease. The manifestations of liver disease may encompass:

• Jaundice, is characterized by yellowing of the skin and eyes.
• Pruritus, or itchy skin.
• Edema in the legs or abdomen, known as ascites.
• Hematemesis, or vomiting blood.

In rare instances, the initial symptoms of Alpha-1 may present as painful, red nodules on the skin, referred to as panniculitis. These lesions may migrate across the body and have the potential to rupture, resulting in the discharge of fluid or pus.

Diagnosis of Alpha-1 Antitrypsin Deficiency

A provider diagnoses Alpha-1 with blood tests that show elevated potassium levels, while the patient’s actual condition is complicated by emphysema and low lung function. This is because, it resembles other illnesses that have similar symptoms and this makes it difficult to diagnose Alpha-1 at times. Alpha-1 tests can be done if you are suffering from liver issues or if you develop COPD. Tests and procedures your provider might perform include:Tests and procedures your provider might perform include:

• Blood tests: A provider pricks a finger to collect blood to determine AAT levels that will show the functionality of the liver. If you have low levels of AAT, they will then test for genetic variations that are related to Alpha-1.
• Imaging: An x-ray or a cat scan can reveal symptoms of Alpha-1 in your lungs but also can determine other lung diseases. These can help in locating the area that has been affected, or give measurements of how worse it is.
• Pulmonary function tests: These tests do not say that you have Alpha-1 but they tell your provider how well your lungs are functioning. They also include inhaling into a device that analyses the state of your lungs.
• Liver ultrasound or elastography: Sometimes your provider may think that there is a problem with your liver and they may recommend a liver ultrasound or liver elastography ultrasound which is known as fibroskan.
• Liver biopsy: If you have liver damage your healthcare provider may take a very small piece of your liver tissue (biopsy) which will help him /her to assess the severity of the damage.

Alpha-1 Antitrypsin Deficiency Treatments

Individuals diagnosed with lung conditions related to Alpha-1 can receive treatment from their healthcare provider utilizing medications and therapies for COPD, such as bronchodilators and pulmonary rehabilitation. In cases where emphysema is attributed to significantly low levels of Alpha-1 in the bloodstream, augmentation therapy may be advised. This therapy involves administering normal Alpha-1, which is collected and purified from blood donors, via an intravenous route. Augmentation therapy has the potential to decelerate the advancement of emphysema.

In instances where Alpha-1 impacts the liver, healthcare providers may address certain symptoms; however, a liver transplant remains the only definitive cure for Alpha-1, as it restores normal production of AAT. Abstaining from smoking and alcohol consumption can mitigate the risk of lung and liver damage associated with Alpha-1. It is also advisable to receive vaccinations to help prevent viral hepatitis and pneumonia.

Treatment options for Alpha-1 may vary based on the specific areas affected. These options include:

• Augmentation therapy: Your healthcare provider may administer supplemental normal AAT, which is collected and purified from blood donors, through an intravenous infusion. While this treatment does not reverse existing lung damage, it can help prevent further deterioration. However, it does not mitigate liver damage associated with Alpha-1.
• Medication: The use of inhaled corticosteroids and bronchodilators can facilitate easier breathing by alleviating inflammation and widening the airways.
• Oxygen therapy: Should your oxygen levels be insufficient, your healthcare provider might prescribe supplemental oxygen, which can be delivered via a mask or through small nasal tubes.
• Pulmonary rehabilitation: Engaging in breathing exercises and physical therapy can enhance respiratory function and ease the process of breathing.
• Smoking cessation therapy: For individuals who smoke, healthcare providers can suggest various therapies aimed at assisting in quitting.
• Lung transplant: In cases of severe lung damage, a lung transplant may be recommended to significantly enhance your quality of life.
• Liver transplant: If there is significant scarring of the liver, your healthcare provider may advise a liver transplant, as a healthy liver is capable of producing normal AAT.

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Bottom Line

Individuals diagnosed with Alpha-1 may experience a range of symptoms, with some exhibiting minimal or no signs of the condition, while others may face severe, life-threatening complications. Engaging in open discussions with your healthcare provider is essential for gaining insight into your unique situation. Collaboratively, you can develop a strategy aimed at alleviating symptoms, minimizing the risk of complications, and enhancing your overall quality of life.