Title: Genetic testing should be performed after the first attack of pancreatitis in children
Abstract: Hereditary pancreatitis is a rare, autosomal dominant disorder characterized by acute pancreatitis, chronic pancreatitis and a very high risk for pancreatic cancer. Over 300 families have been identified, with the majority originating in Europe. The cause of most of the cases is from mutations in the cationic trypsinogen gene, or PRSS1. The three most common mutations are R122H, N29I and R122C. The mutations are thought to cause gain-of-function mutations so that trypsinogen is either more easily activated, or active trypsin has delayed degradation. Research focused on the amino acids mutated in hereditary pancreatitis teach us about the central role of trypsin in the initiation of acute pancreatitis, and how the pancreas is normally protected from trypsin. The link between SPINK1 and trypsin activation further supports these concepts. Hereditary pancreatitis also teaches us about chronic pancreatitis. In this case, chronic pancreatitis develops in patients with recurrent acute pancreatitis. The unifying sentinel acute pancreatitis event (SAPE) model is reviewed. There are several major unanswered questions. First, how are 20% of the individuals who inherit the hereditary pancreatitis gene protected from ever getting an attack of pancreatitis? Secondly, what is the cause of the pancreatitis in the 35–40% of patients who do not have trypsinogen mutations? Third, what determines the severity of pancreatitis in those who develop pancreatitis? Finally, with knowledge of the mechanisms leading to pancreatitis, what can be done to limit or prevent damage from this disease?
Publication Year: 2014
Publication Date: 2014-06-01
Language: en
Type: article
Indexed In: ['crossref']
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