Alpha-1 Week

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General Information

Alpha-1 Week

Alpha-1 anti-trypsin deficiency is the most prevalent potentially fatal genetic disorder of adult Caucasians in the United States. An estimated 25 million individuals carry deficiency genes and over 100,000 Americans have alpha-1 deficiency. Yet less than 10% are diagnosed.  Laurell and Eriksson performed the pioneering work and discovered the absence of the Alpha-1 band in serum electrophoresis gels. The normal Alpha-1 anti-trypsin (A1A) protein phenotype is M and 95% is made in the liver. The main function of A1A is to neutralize/control neutrophil elastase a potent proteolytic enzyme able to damage the elastin matrix of the lung. The inheritance is autosomal  co-dominant.

The PiZ protein results from a point mutation that encodes a single amino acid substitution. The Z protein misfolds, polymerizes and accumulates in the liver, where it can damage the liver leading to cirrhosis and hepatoma.  Secretion of A1A from the liver is impaired and low serum levels can lead to lung disease. COPD is a common chronic lung disease in which A1A deficiency is not rare: in 965 emphysema patients 1.9% was Pi*ZZ and 8% were Pi*MZ or carriers. 

The clinical presentation of A1A deficiency from two outpatient registries reveals the following: 54% have emphysema, 72% have respiratory symptoms, and 45% with chronic bronchitis, 35% had a diagnosis of asthma. Also the presence of bronchiectasis in the A1A population is also very common.

On clinical presentations A1A patients often are short of breath and have hyperinflation of the lungs. Usually smoking related emphysema is predominately in apical lung whereas   20% of Alphas showed a classic finding on chest x-ray of emphysema at the base. A review of 102 cat scans showed 64% have basal disease. But it is essential to remember that clinical findings, CT scans and chest x-rays do not identify Alpha-1 deficiency. The diagnosis is made by testing of the serum and this is provided free of charge by the Alpha-1 Foundation at testing centers at the University of Florida and Medical University of South Carolina the site of the registry for A1A deficiency.

It is also important to note that patients have various therapeutic options. The A1A Foundation has designated 80 clinical resource centers across the country to serve patients with this condition. While there are no specific treatments to prevent Alpha-1 disease at present, augmentation or replacement therapy has been shown to be effective on the lung disease at least retrospectively in the NIH Registry. Similarly liver disease is undergoing intense investigation at the present time. Patients with A1A deficiency must assume a liver protective lifestyle Guidelines for clinical care of patients with either lung and liver diseases or both are available.

Who should be tested? All subjects with COPD, regardless of smoking history, all adults with asthma characterized by incompletely reversible airflow, patients with bronchiectasis, chronic liver disease and panniculitis.. The lab testing involves a finger stick and phenotyping or Pi-typing of the protein is done. This can determine whether the patient is a carrier or homozygous (ZZ) for the deficiency. Genotyping is DNA testing that determines the Pi genes from extracted DNA.

Augmentation therapy is now available, there are four approved drugs: Aralast, Glassia, Prolastin, Zemaira. These agents given intravenously each week were approved based on pharmacokinetic and biochemical data under the FDA orphan disease regulatory process. Many studies such as the NIH Registry support the use of augmentation therapy but intense research continues into new products using different routes of administration.

Both the ATS and Alpha1 Foundation recognize the critical importance of targeted research, comprehensive education, unrelenting advocacy and excellence in clinical care of patients with the A1A deficiency.

Four Facts About Alpha-1

  1. Alpha-1 Antitrypsin Deficiency (Alpha-1) is a genetic condition – passed on from parents to their children through genes.

  2. Alpha-1 may result in serious lung disease in adults and/or liver disease at any age.

  3. Alpha-1 has been identified in virtually all populations. About 1 in every 2,500 Americans has Alpha-1.

  4. Alpha-1 is the most common known genetic risk factor for emphysema, and a leading cause of liver transplants in children.