Alpha-1 Antitrypsin Deficiency

Alpha-1 antitrypsin deficiency is a rare inherited disorder characterized by the deficiency, reduced levels, or deficient transport of the Alpha-1 antitrypsin enzyme(AAT). It is a protein made by the liver and protects the lungs from the detrimental effects of irritants and infectious agents. The absence of this protective protein predisposes a person to develop lung disease manifested by the symptoms of shortness of breath, wheezing, cough, etc. The liver also gets affected by the build-up of proteins which may cause jaundice and scarring of the liver. 

It is diagnosed by measuring the levels of AAT protein in the blood. Treatment for lung disease involves cessation of smoking, vaccinations against common lung infections, bronchodilators, intravenous alpha1-antitrypsin, supplemental oxygen if needed, and physical rehabilitation programs. 

Alpha 1 antitrypsin deficiency is a genetic disorder passing from parents to children caused by mutations in the genes. Mutations are changes in the normal genetic constitution that results in the production of abnormal products that do not function normally, causing diseases. In a normal person, upon exposure to an irritant or infective agent, an inflammatory reaction occurs that is kept in balance with the AAT protein, the absence of which results in extra damage to the lung tissue (alveoli). In some people, the protein is produced by the liver but is not transported to the lungs and builds up in the liver causing liver diseases like hepatitis, jaundice, cirrhosis, and liver cancer. 

The disorder affects 1 per 3000-5000 people in the USA. It is more common in white people and affects males and females equally. Lung problems start to appear between the ages of 20 and 50 years. Liver problems may arise early, and their risk increase with age. 

Your risk of getting the disease is increased due to the following factors;

• Genetics- Family history
• Tobacco smoking
• Exposure to environmental dust.
• Excessive alcohol use

Some people may not develop any disease and may not show any symptoms. Some people may show symptoms similar to chronic obstructive pulmonary disease (COPD), including emphysema. While in others, symptoms related to the liver or the skin may appear. They include;

Symptoms related to lungs:

• Breathing difficulties- shortness of breath, especially on exertion
• Cough and wheezing
• Recurrent cold or lung infections
• Usual tiredness
• Unexplained weight loss

Liver symptoms:

• Bruising of the skin
• Yellowish discoloration of the skin and eyes called jaundice
• Accumulation of fluid around the belly and in the legs causing swelling
• Vomiting blood

Skin

Rarely, do some people develop painful red lumps in the skin, known as panniculitis. 

Many people with the disorder are often misdiagnosed with COPD or asthma due to common symptoms. When patients do not respond to regular treatment, then the following tests are ordered to make the diagnosis;

Blood test: You will be asked to submit a sample of your blood to check for the presence of the AAT enzyme, its levels, and its types.

Imaging tests: X-rays and high-resolution CT scans of the lungs are often ordered to visualize the damaged areas of the lungs and the severity of the disease.  

Genetic tests: This test can be performed on your blood to check for the abnormal genes causing the disease.

Liver biopsy: A sample of your liver may be taken to check for fibrosis of the liver.  

The symptoms often resemble some other disorders like;

• Chronic Obstructive Pulmonary Disease (COPD)
• Bronchiectasis
• Chronic Cough
• Chronic asthma
• Pulmonary Embolism (PE)
• Bronchitis
• Cystic Fibrosis
• Emphysema
• Kartagener Syndrome- Primary Ciliary Dyskinesia
• Autoimmune Hepatitis
• Viral Hepatitis

If you experience the symptoms of AAT deficiency, you should consult your healthcare provider. Your doctor will guide you regarding diagnosis and further treatment.

The goals of treatment are to slow down the progression of the disease and provide medical care and support by the following;

• Smoking cessation: First and foremost advice given is to quit smoking.
• Improvement of lung function: To improve lung function, bronchodilators such as ipratropium bromide and short-acting beta-adrenergic agents are given.
• Prevention of respiratory infections: You may be advised to receive vaccination against Pneumonia and influenza to prevent respiratory infections.
• Oxygen therapy: Supplemental oxygen is given if the patient shows low oxygen levels in the blood.
• Antibiotics: This is not the first-line treatment but helps treat bacterial infections since patients with AAT deficiency are more susceptible to lung infections.
• Lung transplant: In severe cases, transplantation with a healthy lung is offered
• Liver transplant: In severe cases, transplantation with a healthy liver is offered. Vaccination with hepatitis A and B vaccines is recommended to prevent further damage to the liver.
• IV alpha antitrypsin enzyme: You may be given AAT protein via a vein to improve its levels in your blood.
• Prevention and Rehabilitation: You may be advised to perform some exercises and adopt healthy habits to help you cope with the disease and improve your quality of life. To help you keep on track, several rehabilitation programs and centers are operating that focus on educating patients on maintaining a healthy lifestyle. These programs are based on counseling, education, fitness training, and nutrition advice. Pulmonary rehabilitation decreases the number of readmissions and improves your quality of life.

The outcome of the disease depends upon the presence of symptoms and the severity of the disease. Some people may not have severe illnesses and have a normal life span. Some people may show serious symptoms and develop complications like emphysema, bronchiectasis, and liver cirrhosis. By following a proper regimen and smoking cessation, the outcome is improved. 

By following a healthy lifestyle, you can cope with the illness;

• Quit smoking
• Try to avoid exposure to environmental pollutants by using face masks.
• Eat healthy foods
• Take care of your oxygen and lung exercises
• Stick to regular exercise
• Avoid excessive use of alcohol to prevent liver problems.
• Stay especially careful in your appointments and adherent to the treatments given.
• Keep track of your vaccination.

Our clinical experts continually monitor the health and medical content posted on CURA4U, and we update our blogs and articles when new information becomes available. Last reviewed by Dr.Saad Zia on May 11, 2023. 

References

https://www.nhlbi.nih.gov/health/alpha-1-antitrypsin-deficiency#:~:text=Alpha%2D1%20antitrypsin%20(AAT),This%20can%20lead%20to%20COPD.

https://www.sciencedirect.com/science/article/pii/S0168827821022273