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Review
. 2007 Jan 4:2:1.
doi: 10.1186/1750-1172-2-1.

Hereditary chronic pancreatitis

Jonas Rosendahl  1 , Hans Bödeker, Joachim Mössner, Niels Teich
Affiliations
Review

Hereditary chronic pancreatitis

Jonas Rosendahl et al. Orphanet J Rare Dis. .

Abstract

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.

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Figures

Figure 1
Figure 1
Diagrammatic illustration of genetic and environmental factors with their suspected influence on the pathogenesis of chronic pancreatitis. Abbreviations: ACP = alcoholic chronic pancreatitis, TCP = tropical calcific chronic pancreatitis, ICP = idiopathic chronic pancreatitis, HCP = hereditary chronic pancreatitis; abbreviations of the genes see within the text (According to Witt, [85]).
Figure 2
Figure 2
Linear map of pancreatitis associated mutations within the primary structure of the human cationic trypsinogen. The amino-acid positions affected by the pancreatitis-associated PRSS1 mutations are denoted by asterisks (*). The positions of the most frequent N29I and R122H mutations are indicated. The blue call-out demonstrates the sequence of the trypsinogen activation peptide (TAP) and the mutations found in this region. The highly conserved tetra-aspartate motif in the activation peptide is underlined and bold.
Figure 3
Figure 3
Model of inherited pancreatitis. In the normal pancreas (left) trypsin that is prematurely activated within the pancreas is inhibited by SPINK1 and in the second line by trypsin and mesotrypsin preventing autodigestion. In inherited pancreatitis (right) mutations in PRSS1 or SPINK1 lead to an imbalance of proteases and their inhibitors resulting in autodigestion. The role of CFTR is until now poorly understood. Abbreviations: AP = activation peptide (According to Witt, [85]).
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