Hereditary chronic pancreatitis Jonas

Hereditary chronic pancreatitis (HCP) is a very rare form of early onset chronic pancreatitis. With the exception of the young age at diagnosis and a slower progression, the clinical course, morphological features and laboratory findings of HCP do not differ from those of patients with alcoholic chronic pancreatitis. As well, diagnostic criteria and treatment of HCP resemble that of chronic pancreatitis of other causes. The clinical presentation is highly variable and includes chronic abdominal pain, impairment of endocrine and exocrine pancreatic function, nausea and vomiting, maldigestion, diabetes, pseudocysts, bile duct and duodenal obstruction, and rarely pancreatic cancer. Fortunately, most patients have a mild disease. Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin, and thus probably cause premature, intrapancreatic trypsinogen activation disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes, such as the anionic trypsinogen (PRSS2), the serine protease inhibitor, Kazal type 1 (SPINK1) and the cystic fibrosis transmembrane conductance regulator (CFTR) have been found to be associated with chronic pancreatitis (idiopathic and hereditary) as well. Genetic testing should only be performed in carefully selected patients by direct DNA sequencing and antenatal diagnosis should not be encouraged. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications, such as pseudocysts, bile duct or duodenal obstruction. The disease course and prognosis of patients with HCP is unpredictable. Pancreatic cancer risk is elevated. Therefore, HCP patients should strongly avoid environmental risk factors for pancreatic cancer. Disease name/synonyms Hereditary chronic pancreatitis Definition/diagnostic criteria Genetic definition Already in 1952 Comfort and Steinberg were first to recognize that chronic pancreatitis may accumulate in selected families suggesting a genetic background [1]. Thereafter, hereditary chronic pancreatitis (HCP) was defined as an autosomal dominant disease with a penetrance of approximately 80%. However, in the daily clinical setting the inheritance pattern cannot be determined in some cases. In 1996 several groups mapped a gene for HCP to chromosome 7 [2-4]. In the same year, Whitcomb and colleagues identified an R122H mutation in the cationic trypsinogen gene (PRSS1) [5]. Several other mutations were described subsequently (A16V, D22G, K23R, N29I, N29T, R122C) [6-12]. Until now, the R122H and Published: 04 January 2007 Orphanet Journal of Rare Diseases 2007, 2:1 doi:10.1186/1750-1172-2-1 Received: 25 November 2006 Accepted: 04 January 2007 This article is available from: http://www.OJRD.com/content/2/1/1 © 2007 Rosendahl et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.