Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

alpha 1AT should no longer be ignored by hepatologists with regard to its role in protecting the liver from injury. This protective role needs further definition with regard to protease inhibition, immunologic control, and functional inactivation. Severe deficiency of alpha 1AT clearly predisposes to definable types of liver disease not only in infants and children, but at the other end of the spectrum in elderly adults. It is unfortunate that the pathophysiology of human and animal alpha 1AT related liver injury is not as readily apparent as in pulmonology conditions. However, it is time to digest the tremendous progress that has evolved in that field in relating alpha 1AT to emphysema. Cirrhosis of the liver should be studied in relationship to the pathophysiology demonstrated by our colleagues to be important in "cirrhosis of the lung." The diagnosis of alpha 1AT deficiency and the course of the associated liver disease have been reviewed and updated. Prevention and cure have been demonstrated to be possible but neither method has universal applicability. In contrast, other potential therapeutic endeavors, although not presently proved to be efficacious, with time and research will provide methodologies for the treatment of this disorder as well as insight into mechanisms of general liver injury not previously appreciated.
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PMID:Alpha-1-antitrypsin: an ignored protein in understanding liver disease. 676 44

alpha 1-Antitrypsin (AAT) deficiency, also known as alpha 1-antiprotease inhibitor deficiency, is a disease caused by genetically determined AAT deficiency. It occurs as a result of inheritance of two protease inhibitor (PI) deficiency alleles from the AAT gene locus (designated PI) on chromosomal segment 14q32.1. The most common deficiency allele is PI*Z and a large majority of individuals with severe AAT deficiency are PI type ZZ. The disease occurs predominantly in white persons of European origin and its frequency in Europe and North America is comparable to that of cystic fibrosis (1 in 2000 to 1 in 7000.) Persons with AAT deficiency may have no clinical manifestations. Chronic obstructive pulmonary disease (COPD) with a high frequency of panacinar emphysema is the most prevalent clinical disorder associated with AAT deficiency and the most frequent cause of disability and death. Tobacco smoking is the major risk factor for developing COPD, which generally begins by the third decade of life, much earlier than "usual" COPD that occurs in AAT-replete individuals. Liver disease, the second most frequent clinical manifestation of AAT deficiency, typically presents as cholestasis in infancy but is usually not severe and generally remits by adolescence. Chronic liver disease develops infrequently, although AAT deficiency is the commonest cause of chronic liver disease in childhood. Cirrhosis and carcinoma of the liver affect at least 25% of AAT-deficient adults over the age of 50 years. AAT deficiency appears to be widely underdiagnosed and based on predicted gene frequencies even in the most intensely studied populations, only a small proportion of those predicted to have AAT deficiency have been diagnosed. Human AAT is available in limited quantity for augmentation therapy. This Memorandum summarizes the discussions and recommendations made by participants at a WHO meeting held in Geneva on 18-20 March 1996 to review existing knowledge about this highly prevalent genetic disorder, develop a strategy for enhancing awareness of it among health-care-givers and the general public, and explore new case-finding and disease-prevention strategies.
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PMID:Alpha 1-antitrypsin deficiency: memorandum from a WHO meeting. 944 74