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Alpha1-antitrypsin (AAT) deficiency is a relatively rare genetic disorder characterized by reduced serum levels of AAT. This genetic defect most often leads to polymerization of the AAT protein within the hepatocytes, leading to both accumulation of the protein within the hepatocytes and to decreased release of the protein into circulation.
Of the 80,000-100,000 people estimated to have AAT deficiency in the US, less than 5% have been diagnosed. Do your part to identify people with AAT deficiency by ordering your free AlphaKit today.
Circulating AAT is normally distributed to the lungs, where it is believed to serve an essential protective function against the destruction of elastin, a protein that supports the lung function. Individuals with low levels of circulating AAT are at increased risk for pulmonary problems, particularly emphysema, manifesting as early as the 3rd or 4th decade, which shortens life expectancy. Other manifestations of AAT deficiency include neonatal hepatitis, hepatitis, cirrhosis, and panniculitis |
Clinical Conditions Associated With AAT Deficiency
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Emphysema |
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COPD |
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Bronchiectasis |
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Chronic bronchitis |
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Neonatal hepatitis |
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Jaundice |
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Cirrhosis (children and adults) |
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Chronic active hepatitis |
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Necrotizing panniculitis (rare) |
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Lung and Liver Disease
AAT is a protease inhibitor produced principally in the liver and is found in the blood and epithelial lining fluid (ELF) of the lungs. AAT can inhibit the activity of several proteolytic enzymes; however, its primary substrate is neutrophil elastase. AAT is the most abundant antiprotease in the human circulation, and provides more than 90% of the protection against neutrophil elastase in the lower respiratory tract.1
Under normal conditions, neutrophil elastase is part of a secondary lung defense in response to infection or inflammation. However, if not neutralized by AAT, neutrophil elastase can destroy healthy lung tissue. Over time, this process can result in irreversible destructive enlargement of the airways and alveoli with or without fibrosis, ie, emphysema.2,3
Therefore, people with AAT deficiency are at high risk for the development of emphysema.
Although lung disease is the most common manifestation of AAT deficiency, accumulation of the protein within hepatocytes can precipitate liver disease in some patients. When liver disease develops, it usually manifests in infants as jaundice and hepatitis. However, liver disease may also appear in older children or adults as mild to severe hepatitis or cirrhosis. In rare instances, patients manifest significant lung and liver disease concomitantly.
Infrequently, panniculitis, a severe inflammation of subcutaneous fatty tissue, may develop in patients with AAT deficiency.
References:
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Crystal RG. alpha1-antitrypsin deficiency: pathogenesis and treatment. Hosp Pract. 1991;81-94. |
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Stockley RA. Neutrophils and protease/antiprotease imbalance. Am J Resp Crit Care Med. 1999;160:S49-S52. |
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O’Byrne PM, Postma DS. The many faces of airway inflammation: asthma and chronic obstructive pulmonary disease. Am J Resp Crit Care Med. 1999;159:S41-S63. |
Important Safety Information
Prolastin®, Alpha1-Proteinase Inhibitor (Human) is indicated for chronic replacement therapy of individuals having congenital deficiency of alpha-1 PI (alpha1-antitrypsin deficiency) with clinically demonstrable panacinar emphysema. Weekly Prolastin® therapy has demonstrated a low occurrence of side effects. In clinical studies with Prolastin®, reactions were observed in 1.16% of infusions, the most common events being fever (0.77%), light-headedness (0.19%), and dizziness (0.19%). As with all plasma-derived therapeutics, the potential to transmit infectious agents cannot be totally eliminated. Individuals with selective IgA deficiencies who have known antibody against IgA (anti-IgA antibody) should not receive Prolastin®, since these patients may experience severe reactions, including anaphylaxis, to IgA which may be present.
You are encouraged to report negative side effects of prescription drugs
to the FDA. Visit www.fda.gov/medwatch, or call 1-800-FDA-1088.
Please click here for Prolastin® full Prescribing Information.
Remember, your doctor or healthcare provider is the single best source of information regarding you and your health. Please consult your doctor or healthcare provider if you have any questions about your health or any of your medications.
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