Genetic issues in pediatric pancreatitis
The number of hospitalizations in children with acute and chronic pancreatitis is increasing and accounts for significant morbidity. Acute pancreatitis is a reversible event involving diffuse inflammation of the pancreas with variable involvement of other regional tissues, remote organs, or both, whereas chronic pancreatitis is a process that produces irreversible changes in the pancreatic structure and function. Mutations in the gene encoding cationic trypsinogen have recently been identified to be associated with hereditary pancreatitis. Genetic mutations in the pancreatic secretory trypsin inhibitor and the cystic fibrosis transmembrane conductance regulator have been described to play a role in the development of pancreatitis as well. Mutations in the cytokine target genes relating to regulation of inflammation are likely to be important in determining the severity of pancreatitis. These findings, along with the advances in cell biology, have contributed to a better understanding of the pathophysiology of pancreatic diseases.
KeywordsPancreatitis Acute Pancreatitis Chronic Pancreatitis Acute Pancreatitis Hereditary Pancreatitis
Unable to display preview. Download preview PDF.
References and Recommended Reading
- 2.Rinderknecht H: Pancreatic secretory enzymes. In The Pancreas: Biology, Pathobiology, and Disease. New York: Raven Press; 1993:219–251.Google Scholar
- 3.Whitcomb DC: Early trypsinogen activation in acute pancreatitis. Gastroenterology 1999, 116:770–773.Google Scholar
- 11.Schneider A, Whitcomb DC: Hereditary pancreatitis: a model for inflammatory diseases of the pancreas. Best Pract Res Clin Gastroenterol 2002, 16:347–363. This review discusses the genetic studies on kindreds with HP and reviews the theories on development of chronic pancreatitis.PubMedCrossRefGoogle Scholar
- 13.Khalid A, Finkelstein S, Thompson B, et al.: A 93 year old man with the PRSS1 R122H mutation, low SPINK1 expression and without pancreatitis: insights into phenotypic non-penetrance. Gut 2005. Dec 14; [Epub ahead of print].Google Scholar
- 20.Oralewska B, Oracz G, Sobczynska-Tomaszewska A, et al.: Hereditary pancreatitis in children: SY1-02. J Pediatr Gastroenterol Nutr 2005, 40:630.Google Scholar
- 28.Whitcomb DC: Value of genetic testing in the management of pancreatitis. Gut 2004, 53:1710–1717. Excellent review of the role of genetic factors in the development of pancreatitis. The author provides possible mechanisms of recurrent acute and chronic pancreatitis in the context of heterozygous CFTR mutations.PubMedCrossRefGoogle Scholar
- 30.De Boeck K, Weren M, Proesmans M, Kerem E: Pancreatitis among patients with cystic fibrosis: correlation with pancreatic status and genotype. Pediatrics 2005, 115:463–469. This recent study describes the occurrence and outcomes of pancreatitis in both pancreatic-sufficient and pancreatic-insufficient patients with CF.CrossRefGoogle Scholar
- 39.Noone PG, Zhou Z, Silverman LM, et al.: Cystic fibrosis gene mutations and pancreatitis risk: relation to epithelial ion transport and trypsin inhibitor gene mutations. Gastroenterology 2001, 121:1310–1319. This paper shows that the combination of two CFTR mutations and a SPINK1 mutation increases the risk of pancreatitis 900-fold.PubMedCrossRefGoogle Scholar