Hereditary pancreatitis: new insights, new directions.
Hereditary pancreatitis is an unusual form of acute and chronic pancreatitis with a familial predisposition. Recently, the gene mutations causing most cases of hereditary pancreatitis have been identified in the cationic trypsinogen gene. The known mutations are trypsinogen R117H and N211. These may predispose to acute pancreatitis by eliminating one of the fail-safe mechanisms used by the pancreas to eliminate prematurely activated trypsin. Accumulation of active trypsin mutants are hypothesized to initiate a digestive enzyme activation cascade in the pancreatic acinar cells leading to autodigestion, an intense inflammatory response, and acute pancreatitis. The observation that these patients also develop typical chronic pancreatitis and may later develop pancreatic cancer provides strong evidence that these conditions are linked. Knowledge of the pathophysiological conditions leading to acute and chronic pancreatitis and the development of a transgenic mouse expressing the mutant human trypsinogen genes will provide directions and tools necessary for the effective treatment or prevention of this human disease.
Whitcomb
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Division of Gastroenterology and Hepatology, University of Pittsburgh, PA, USA.
Ulrich
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D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D051379:Mice; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D010195:Pancreatitis / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D012680:Sensitivity and Specificity; D014362:Trypsinogen / Q000235:genetics*
D014362:Trypsinogen