Alpha-1 antitrypsin deficiency (alpha-1 antitrypsin) is a genetically inherited condition. Individuals with this deficiency typically have two abnormal alpha-1 antitrypsin genes, one coming from each parent. This abnormality causes the alpha-1 antitrypsin to be released from the liver at a decreased rate, which results in higher than normal levels of inherent protein. Ultimately, the excessive accumulation of alpha-1 antitrypsin in the liver will predispose an individual to liver disease with associated pulmonary disease.
What is Alpha-1 Antitrypsin?
Alpha-1 antitrypsin is a protein that is produced in the liver, which travels throughout the blood stream and functions to protect vital organs against the harmful effects of other proteins. In the lungs, it exerts its protective properties to help prevent inflammation. This inflammation can be caused from infection and/or inhaled irritants, such as tobacco smoke.
The incidence of this disease is approximately 1 in 1,500 to 3,500 individuals. It occurs worldwide, but the prevalence varies by population. It is common for alpha-1 antitrypsin deficiency to go undiagnosed as the symptoms mirror those of both of chronic obstructive pulmonary disease (COPD) and asthma.
The most common signs and symptoms of the deficiency, with lung involvement, include shortness of breath, wheezing, chronic bronchitis, recurring chest colds, less exercise tolerance, year-round allergies, and bronchiectasis. The most common signs and symptoms with liver involvement include unexplained liver disease, elevated liver enzymes, jaundice, swelling of the abdomen or legs, and hyperemesis with blood originating from enlarged veins in the esophagus or stomach.
The diagnosis of alpha-1 antitrypsin deficiency cannot be solely determined by symptoms or physical examination. A blood test is used to confirm the deficiency and is done via a blood draw or finger stick test. The test is simple, quick, and highly accurate. Individuals who are recommended for testing are those with COPD – with or without associated emphysema or bronchitis, unexplained chronic liver disease, unexplained bronchiectasis, necrotizing panniculitis, granulomatosis with polyangiitis, or asthma that cannot be completely reversed after aggressive treatment. Additionally, it is recommended that individuals with parents, siblings, children, or extended family members who are identified with an abnormal alpha-1 gene proceed with testing.
Treatment of Alpha-1 Antitrypsin Deficiency
The only specific therapy for alpha-1 antitrypsin deficiency is augmentation, or replacement, therapy. The treatment plan should include:
- Initial lung function tests and chest computed tomography (CT) scan, with annual spirometry
- Evaluation for appropriate antibiotic use
- An immunization program including viral hepatitis and influenza strains
- Reduction or elimination of environmental risk factors
- Appropriate inhaled medications
- An exercise program
- Oxygen, if needed
The main goal of augmentation therapy is to supplement the deficient alpha-1 protein in the lungs. This will increase the level of alpha-1 protein in order to protect the lungs from destructive effects of neutrophil elastase; a white blood cell released by the body in response to inflammation or infection.
Alpha-1 antitrypsin therapy is considered ongoing and lifelong. Therapy cannot restore lung function that has already been lost and it is not considered a cure. In addition, evidence exists that supports augmentation therapy being able to reduce the frequency and severity of pulmonary exacerbations; a secondary benefit.
Augmentation therapy is recommended for any individual with Alpha-1 related lung disease. However, the COPD Foundation guidelines suggest that individuals with clinically worsening lung function, an Forced Expiratory Volume (FEV1) less than or equal to 65%, have obtained greater benefits.
There are four augmentation therapy medications available and approved by the FDA in the United States, including:
- Aralast NPTM
The recommended dose for these medications is 60 mg/kg IV weekly. The most common side effects reported are fatigue and flu-like symptoms that typically last up to 24 hours post infusion. These side effects can normally be reduced or stopped by slowing down the infusion rate.
Before starting these treatments, a patient should be tested for immunoglobulin A (IgA) deficiency. This is a heredity condition that can potentially cause a severe allergic reaction to plasma products. In addition, it is recommended that immunization against both Hepatitis A and B be considered to reduce the risk of liver damage.
Accredo’s immune disorders care team dedicated to alpha-1 antitrypsin deficiency understands the difficulty of coping with this complex condition. We work diligently to coordinate solutions for the challenges you face. Whether teaching you how to administer therapy, providing side effects counseling, or coordinating with physicians to determine a care plan – we understand patients’ unique therapy needs.
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