Alpha-1 Antitrypsin Deficiency
Return to Library
What is alpha-1 antitrypsin deficiency?Alpha-1 antitrypsin deficiency is an inherited disorder that can cause lung disease in adults and liver disease in adults and children. The first signs and symptoms of lung disease caused by alpha-1 antitrypsin deficiency usually appear between ages 20 and 50. The earliest symptoms are shortness of breath following mild activity, reduced ability to exercise, and wheezing. Other signs and symptoms can include unintentional weight loss, recurring respiratory infections, fatigue, rapid heartbeat upon standing, and vision abnormalities. Advanced lung disease leads to emphysema, in which small air sacs in the lungs (alveoli) are damaged. Characteristic features of emphysema include difficulty breathing, a hacking cough, and a barrel-shaped chest. Smoking or exposure to tobacco smoke accelerates the appearance of symptoms and damage to the lungs. About 10 percent of infants and 15 percent of adults with alpha-1 antitrypsin deficiency have liver damage. Signs of liver disease can include a swollen abdomen, swollen feet or legs, and yellowing of the skin and whites of the eyes (jaundice). In rare cases, alpha-1 antitrypsin deficiency also causes a skin condition known as panniculitis, which is characterized by hardened skin with painful lumps or patches. Panniculitis varies in severity and can occur at any age. How common is alpha-1 antitrypsin deficiency?Alpha-1 antitrypsin deficiency occurs worldwide, but its prevalence varies by population. For example, in Scandinavia this disorder affects 1 in 1,500 to 3,000 individuals, but it is less common in Asian and black populations. In North America, alpha-1 antitrypsin deficiency affects 1 in 5,000 to 7,000 people. What genes are related to alpha-1 antitrypsin deficiency?Mutations in the SERPINA1 gene cause alpha-1 antitrypsin deficiency. The SERPINA1 gene provides instructions for making a protein called alpha-1 antitrypsin. This protein protects the body from being damaged by a powerful enzyme called neutrophil elastase. Neutrophil elastase is released from white blood cells to fight infection, but it can attack normal tissues (such as lung tissue) if not carefully controlled by alpha-1 antitrypsin. Mutations in the SERPINA1 gene can lead to a shortage (deficiency) of alpha-1 antitrypsin protein or an abnormal form of the protein that cannot control neutrophil elastase. Uncontrolled, neutrophil elastase destroys alveoli, which can lead to emphysema. The abnormal form of alpha-1 antitrypsin can also accumulate in the liver and may damage this organ. How do people inherit alpha-1 antitrypsin deficiency?This condition is inherited in an autosomal codominant pattern. Codominance means that two different versions of the gene may be expressed, and both versions contribute to the genetic trait. The most common version (allele) of the SERPINA1 gene, called M, produces normal levels of the alpha-1 antitrypsin protein. Most people have two copies of the M allele (MM) in each cell. Other versions of the SERPINA1 gene lead to reduced levels of alpha-1 antitrypsin. For example, the S allele produces moderately low levels of this enzyme, and the Z allele produces very little alpha-1 antitrypsin. Individuals with two copies of the Z allele (ZZ) in each cell are likely to have alpha-1 antitrypsin deficiency. Those with the SZ combination have an increased risk of developing lung disorders (such as emphysema), particularly if they smoke. Worldwide, about 161 million people have one copy of the S or Z allele and one copy of the M allele in each cell (MS or MZ). Individuals with a MS (or SS) combination usually produce enough alpha-1 antitrypsin to protect the lungs. People with MZ alleles, however, have a slightly increased risk of impaired lung or liver function.
Source: National Institutes of Health
|
Free Alpha-1 Antitrypsin Deficiency Articles |
|
|
|
|
Committee for Orphan Medicinal Products
2007 MAR 5 -- The seventy-sixth meeting of the Committee for Orphan Medicinal Products (COMP) took place on 6-7 February 2007. The Committee was delighted to officially welcome Prof. Bjorn Beerman as the new COMP member nominated by Sweden. COMP Opinions The Committee adopted 7 positive opinions on orphan medicinal product designation during this meeting: * Elafin, from Proteo Biotech AG, for treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension (review time: day 90) * Enzastaurin hydrochloride, from Eli Lilly Nederland B.V., for treatment of diffuse large B cell Lymphoma (review time: day 59) * Hydrocortisone (modified release tablet), from Phoqus Pharmaceuticals Limited, for treatment of adrenal insufficiency (review time: day 59) * Idebenone, from Santhera Pharmaceuticals (Deutschland) AG, for treatment of Duchenne muscular dystrophy (review time: day 90) * Recombinant adeno-associated viral vector containing human alpha-1 antitrypsin gene, from The Matthews Consultancy Ltd, for treatment of congenital alpha-1 antitrypsin deficiency (review time: day 59) * Recombinant human monoclonal antibody to human IL-1beta of the IgG1/K class, from Novartis Europharm Limited, for treatment of cryopirin-associated periodic syndromes (Familial Cold Urticaria Syndrome (FCUS), Muckle-Wells Syndrome (MWS), and Neonatal Onset Multisystem Inflammatory Disease (NOMID), also known as Chronic Infantile Neurological Cutaneous Articular Syndrome (CINCA)) (review time: day 59) * Zanolimumab, from Serono Europe Limited, for treatment of peripheral T-cell lymphoma (nodal, other extranodal and leukaemic/disseminated) (review time: day 59) Two oral explanations on orphan medicinal product designation took place during the meeting. Withdrawals of Orphan Medicinal Product Applications The COMP noted that no applications for orphan medicinal product designation were withdrawn. Overview of orphan designation procedures The European Commission granted five positive decisions on orphan designation1 since the last COMP meeting on 9-10 January 2007 (see Annex 1). The status of orphan designation procedures, to date for 2007, is summarised below: An overview of orphan designation procedures for 2000-2006 is provided in Annex 2. Further information on designated orphan medicinal products is publicly available in the form of summarised COMP Opinions2, which the Agency routinely publishes following adoption of the respective decisions on orphan designation by the European Commission. Date of next COMP meeting The next COMP meeting will be held on 7-8 March 2007. Keywords: Hematology, Hypertension, Lymphoma, Oncology, Pharmaceuticals, European Agency for the Evaluation of Medicinal Pr. This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2007, Biotech Business Week via NewsRx.com.
|
