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The Alpha-1 Foundation, based in Miami, Florida, was founded in 1995 as an advocacy organization for Alphas, individuals with Alpha-1 Antitrypsin Deficiency, and their friends and families. The Foundation is dedicated to providing the leadership and resources that will result in increased research, improved health, worldwide detection, and a cure for Alpha-1. Collaborating with investigators throughout the United States and Europe, the National Institutes of Health (NIH), the Food and Drug Administration (FDA), the pharmaceutical industry, and individuals with Alpha-1, the Alpha-1 Foundation works to expedite the development of improved therapies.

What is Alpha-1 Antitrypsin Deficiency?


Alpha-1 Antitrypsin Deficiency (Alpha-1) is a genetic disorder characterized by the production of an abnormal alpha-1 antitrypsin (AAT) protein. The liver cells cannot secrete the abnormal AAT protein, which accumulates within the cells and results in marked reductions of circulating AAT levels. The build-up of AAT in the liver can lead ro serious liver disease, and the low circulating AAT level leaves the lungs unprotected from the deleterious effects of lung infection and environmental irritants including cigarette smoke, resulting in chronic lung disease Description AAT is a protein that is produced mostly in the liver. Its primary function is to protect the lungs from neutrophil elastase. Neutrophil elastase is an enzyme that normally serves a useful purpose in lung tissue digesting damaged or aging cells and bacteria to promote healing. However, it can also attack healthy lung tissue. AAT, in sufficient amounts, will trap and destroy neutrophil elastase before it has a chance to begin damaging the delicate lung tissue. Consequently, if an individual doesn't have enough AAT secreted from the liver, the neutrophil elastase will damage the lung tissue, causing chronic lung disease. The non-secreted AAT that accumulates in the liver is toxic to the liver cells, and can cause cirrhosis of the liver and liver cancer. Conditions associated with Alpha-1: • Lung disorders: COPD (chronic bronchitis and/or emphysema), bronchiectasis and therapy resistant asthma. These problems are usually seen in adults • Liver disorders: elevated liver enzymes, neonatal hepatitis, chronic liver disease, cirrhosis, and liver cancer. Although less common, Alpha-1 related liver disease can be seen at all ages beginning in infancy. • Panniculitis: a skin condition characterized by hardened skin with painful lumps or patches, created by an excess of inflammatory cells within the fatty lobules of the skin, with or without inflammation of the blood vessels. The severity of this condition varies and can occur at any age. There are other diseases that can cause panniculitis.

Signs and Symptoms

Symptoms Related to the Lungs:

• Shortness of breath • Wheezing or non-responsive asthma • Coughing with or without sputum (phlegm) production • Recurring respiratory infections • Rapid deterioration of lung function • Decreased exercise tolerance (Shortness of breath)

Symptoms Related to the Liver:

• Unexplained liver problems and /or elevated liver enzymes • Eyes and skin turning yellow (jaundice) • Swelling of the abdomen (ascites) • Vomiting or passing blood in the stool • Failure to thrive in children.

Other Symptoms:

• Painful skin nodules • Swelling of legs


For each trait, a person inherits two genes (one gene from each parent). People who have received two defective AAT genes (called Z or S) will be either ZZ (majority), SZ, or SS. In addition, there could be an absence of one or both AAT genes (Z-null, or null-null). The ZZ, ZS, Z-null, null-null genotypes and possibly the SS genotype are characterized very low AAT levels and lung and liver disease. The normal AAT gene is called M. Therefore, the genotype of normal individuals is MM. Current evidence suggests that there are about 100,000 people with the ZZ genotype in the US.

An Alpha-1 carrier is a person who has one normal alpha-1 gene (M) and one defective Alpha-1 gene (usually S or Z). Most Alpha-1 carriers are MS or MZ, and it is believed that over 20 million people in the United States are carriers of one defective AAT gene. Carriers may have lower blood levels of the AAT protein, but their levels are rarely as low as those of people with Alpha-1, decreasing the possibility of liver and /or lung disease. There currently is no proof that MS or MZ carriers suffer lung or liver disease.


Alpha-1 has been identified in virtually all populations and ethnic groups. It is estimated that about 1 in every 2,500 Americans have Alpha-1. Alpha-1 is the most prevalent potentially fatal genetic disorder of adult Caucasians in the U.S., in both men and women.

Alpha-1 related chronic lung disease can be detected as early as in the third decade of life, especially in smokers. Alpha-1 should be suspected in children and adults with unexplained elevated liver enzymes, prolonged clotting tests, chronic active hepatitis or “cryptogenic” cirrhosis.

AAT Deficiency is the leading genetic cause of liver disease in infants and children, and is the second most common indication for liver transplantation in this group in the U.S. The risk of hepatocellular carcinoma is increased in adults with Alpha-1


Family History:

A positive family history of Alpha-1 is the greatest risk factor for Alpha-1; therefore it is important to test all family members of a person with Alpha-1.

Identification of Patients:

Persons with the following conditions or risk factors should be tested:

• COPD • Asthma • Family History of Alpha-1 • Chronic Liver Disease • Bronchiectasis • Panniculitis • Unexplained vasculitis, particularly Wegener’s granulomatosis type • Hepatocellular carcinoma • Any evidence of unexplained liver disease


Alpha-1 can’t be diagnosed by having any particular symptom(s) or by a medical examination; one must be tested using a finger prick (blood spot) test or by having serum levels tested by drawing blood and/or via a buccal swab.

AAT serum levels are normal between 75-150 micrograms/ml (0.075-0.15 grams/ml)

Treatment and Management

Persons with Alpha-1 should avoid risky behaviors such as smoking, or working in pollution filled environments. Persons with Alpha-1 also should avoid indoor or outdoor pollutants, infections, and develop an exercise and nutritional program to minimize stressors. Annual influenza vaccination is strongly advised. While the following therapies can improve quality of life and prevent frequent flare-ups of the disease, only augmentation therapy (regular intravenous infusions of AAT) has the potential of slowing the progression of lung disease. There is no specific treatment for liver disease.

Therapies for Alpha-1 lung and liver disease include:

Lung Disease and Alpha-1:

• Antibiotics • Bronchodilators • Corticosteroids • Supplemental Oxygen • Augmentation Therapy • Pulmonary rehabilitation • Surgery • Lung Volume Reduction • Lung Transplantation

Liver Disease and Alpha-1:

There are several treatment options available that will improve advanced liver disease (caused by the damage of liver tissue) but only liver transplantation will completely cure the disease. Treatment options include:

• Large volume paracentisis (LVP), which is the removal of fluid from the abdomen. • Banding of sclerotherapy of veins in the esophagus to reduce bleeding from the distended or swollen veins. • Portal vein decompression, to reduce pressure in the blood vessels entering the liver from the digestive organs. • Liver transplantation


Alpha-1 Foundation Toll Free: 877-2-CURE-A1 (228-7321) Web Site: <>

Alpha-1 Association Toll Free: 800-521-3025 Web Site: <>

AlphaNet Toll Free: 800-577-ANET (577-2638) Web Site: <>

COPD Foundation Toll Free: 1-866-316-COPD (2673) Web Site: <>


Alpha-1 Foundation Education Materials Working Group. Alpha-1 Foundation. N.p., n.d. Web. 3 Sept. 2009. <>.

Alpha-1 Foundation Education Materials Working Group. “A Guide for the Recently Diagnosed Individual.” Alpha-1 Antitrypsin Deficiency. 2008. Print.

Alpha-1 Foundation Education Materials Working Group. “A Healthcare Provider’s Guide.” Alpha-1 Anitrypsin Deficiency. 2008. Print.

Alpha-1 Foundation Education Materials Working Group. “The Liver and Alpha-1.” Alpha-1 Antitrypsin Deficiency. 2006. Print.



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