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Diagnosing Alpha1 takes a simple test

Early detection can make a difference. Find out about the free Grifols AlphaKit you can order.

Alpha-1 Etiology & Heredity

Etiology

Alpha-1 is caused by decreased plasma levels of alpha1-antrypsin (AAT)

  • Decrease due to inheritance of 2 abnormal alleles, which inhibits the production and release of AAT from the liver1
AAT Monomer Graphic
  • AAT is more than an antiprotease
  • 52kDa glycoprotein2
  • Acute-phase reactant2
  • Anti-inflammatory3,4
  • Secreted in large amount from hepatocytes, but also expressed in macrophages and bronchial epithelium2
  • Broad-spectrum antiprotease3,4
  • Inhibits α-defensin cytotoxicity and proinflammatory properties4
  • Antioxidant with 9 methionines4
  • One function of AAT is to inhibit various serine proteinases2
  • Neutrophil elastase has been identified by kinetic studies as the preferential target2
  • Inhibition occurs when neutrophil elastase binds to the AAT active site to form stable 1:1 equimolar complexes2
  • Smoking significantly increases the risk of emphysema in patients with Alpha-15
  • Failure to secrete functional AAT into circulation also decreases the amount of AAT available for protease activity in the lung, causing unopposed lung damage by neutrophil elastase6-8

Heredity

About 100 alleles have been identified2

  • Pi allele Z (Pi Z) is the most common deficiency allele2
  • Inheritance of 2 Pi Z alleles (Pi ZZ) results in severe Alpha-12
  • Pi allele S (the other common abnormal allele) also occurs through mutation and can cause reduced circulating plasma levels of AAT2

Family risk associated with presence of deficiency allele

Allele Algorithm

Examples of inheritance of AAT-deficient alleles:

A) One parent is homozygous normal (2 M alleles) and one parent is homozygous abnormal alpha-1 (two Z alleles): children have a 100% chance of being a carrier for alpha-1.

B) Both parents are heterozygous carriers of abnormal alleles (one normal M allele and one abnormal Z allele): children have a 25% chance of being an Alpha-1 patient, a 50% chance of being a carrier for Alpha-1 and a 25% chance of having two normal alleles.

Serum AAT levels are lower in patients with abnormal alleles9,10

Range of serum AAT levels by Phenotype

*11 uM AAT level is estimated to be protective.

Largely undiagnosed

Alpha-1 is one of the most prevalent potentially fatal hereditary diseases11

  • While about 100,000 Americans have Alpha-1, 95% of them remain undiagnosed.12
  • Up to 25 million Americans have an abnormal allele (S or Z)11

Testing early is important and easy

  • The average Alpha patient experiences symptoms for more than 8 years and sees 3 doctors before being correctly diagnosed with Alpha-1.
  • This delay is too long, especially considering the destruction of lung tissue prior to diagnosis.
  • Diagnosis is easy with simple blood tests.

Alpha-1 cannot be diagnosed clinically, but is easy to diagnose with the free Grifols AlphaKit

next: Diagnosis & Testing >

Important Safety Information

PROLASTIN-C, Alpha1-Proteinase Inhibitor (Human) is indicated for chronic augmentation and maintenance therapy in adults with emphysema due to deficiency of alpha1-proteinase inhibitor (alpha1-antitrypsin deficiency). The effect of augmentation therapy with any alpha1-proteinase inhibitor (alpha1-PI) on pulmonary exacerbations and on the progression of emphysema in alpha1-antitrypsin deficiency has not been demonstrated in randomized, controlled clinical trials. PROLASTIN-C is not indicated as therapy for lung disease in patients in whom severe Alpha1-PI deficiency has not been established.

PROLASTIN-C may contain trace amounts of IgA. Patients with known antibodies to IgA, which can be present in patients with selective or severe IgA deficiency, have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions. PROLASTIN-C is contraindicated in patients with antibodies against IgA.

The most common drug related adverse reactions during clinical trials in ≥ 1% of subjects were chills, malaise, headache, rash, hot flush, and pruritus.

PROLASTIN-C is made from human plasma. Products made from human plasma may carry a risk of transmitting infectious agents, e.g., viruses, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent.

Please see accompanying PROLASTIN-C Full Prescribing Information for complete prescribing details.

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.

References
  1. Brantly M, Nukiwa T, Crystal RG. Molecular basis of alpha- 1-antitrypsin deficiency. Am J Med. 1988;84(6A):13-31.
  2. American Thoracic Society/European Respiratory Society. American Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency. Am J Respir Crit Care Med. 2003;168(7):818-900.
  3. Köhnlein T, Welte T. Alpha-1 Antitrypsin Deficiency: Clinical Aspects and Management. Bremen, Germany: UNI-MED Verlag AG; 2007.
  4. Brantly M. Alpha1-antitrypsin: not just an antiprotease: extending the half-life of a natural anti-inflammatory molecule by conjugation with polyethylene glycol. Am J Respir Cell Mol Biol. 2002;27(6):652-654.
  5. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease—Updated 2007.Available at: www.goldcopd.org. Accessed February 18, 2008.
  6. Lomas DA, Mahadeva R. Alpha-1 antitrypsin polymerization and the serpinopathies: pathobiology and prospects for therapy. J Clin Invest. 2002;110(11):1585-1590.
  7. Mahadeva R, Shapiro SD. Chronic obstructive pulmonary disease 3: experimental animal models of pulmonary emphysema. Thorax. 2002;57(10):908-914.
  8. Shapiro SD. Proteinases in chronic obstructive pulmonary disease. Biochem Soc Trans. 2002:30(2):98-102.
  9. University of Florida College of Medicine AAT Deficiency Detection Laboratory.
  10. Wise RA. α1-Antitrypsin deficiency. The Merck Manuals Online Medical Library. http://www.merck.com/mmpe/sec05/ch049/ch049b.html#CIHFAGBJ. Accessed July 6, 2008.
  11. de Serres FJ. Worldwide racial and ethnic distribution of alpha1-antitrypsin deficiency: summary of an analysis of published genetic epidemiologic surveys. Chest. 2002;122(5):1818-1829.
  12. Campos MA, Wanner A, Zhang G, Sandhaus RA. Trends in the diagnosis of symptomatic patients with alpha-1 antitrypsin deficiency between 1968 and 2003. Chest. 2005;128(3):1179-1186.