While the absolute number of patients with genetic causes of pancreatitis is small, due to frequent hospitalizations, this remains a significant problem. This month additional information on genetic predisposition for pancreatitis is available (JPGN 2012; 54: 645-50).
Sultan et al (Milwaukee, WI) reviewed the charts of children <18 years with recurrent acute pancreatitis (RAP) and patients with chronic pancreatitis (CP) from 2000-2009. RAP was considered if patient had a minimum of two distinct episodes of acute pancreatitis. Acute pancreatitis was considered the diagnosis if patient had typical symptoms associated with 3-fold elevation of amylase or lipase or imaging changes consistent with acute pancreatitis. CP was defined as a minimum of 2 episodes of acute pancreatitis associated with pancreatic duct abnormalities or pancreatic insufficiency.
Among this cohort of 29 children, 23 (79%) had mutations which have been associated with genetic pancreatitis (GP). Family history was positive in only five patients.
- CFTR mutation in 14 (48%): two had homozygous mutations, six heterozygous, and four had 5 T variants. The importance of a single CFTR mutation in contributing towards pancreatitis is unclear. However, the Wisconsin population has a carrier frequency of 1:32; the striking difference in frequency indicates that even a single mutation may be important in the pathogenesis of RAP.
- SPINK1 (serine protease inhibitor Kazal type 1) in 8 (27%). SPINK1 mutations occur in 1-3% of the general population. It is often a modifying factor rather than an isolated causal factor in the development of RAP. Four of the patients with SPINK1 mutations also had a CFTR mutation.
- PRSS1 (cationic trypsinogen gene) in 7 (24%). Individuals with these mutations are considered to have hereditary pancreatitis, an autosomal disease with incomplete penetrance.
- Only one patient was tested for chymotrypsin C gene (CTRC) –tested negative.
Seven patients with RAP did not undergo genetic testing & were excluded from the study. These patients had other known causes of RAP: 3 had gallstones, 2 had pancreas divisum, 1 had a metabolic disorder, and 1 had a medication-induced pancreatitis. The authors note, however, that patients with pancreas divisum have had genetic mutations identified in other studies.
- www.uni-leipzig.de/pancreasmutation. This link will take you to the hereditary pancreatitis database where you can search for the specific mutation you identified and find articles dealing with a variety of aspects of that particular mutation.
- 2011 Naspghan Postgraduate Course:
-1st bout, check U/S, trig
-if 2nd bout, suggested to check MRI, genetics (SPINK1, PRSS1, CFTR), sweat test, fecal elastase, possibly IgG4/ANA
- -Gastroenterology 2006; 131: 1844. Mouse model w R122H Trypsiongen expression.
- -Whitcomb DC. Gut 2004; 53: 1710-17. test for PRSS1 (cationic trypsinogen), SPINK1 (Serine protease inhibitor, Kazal Type 1), and CFTR gene.
- -JPGN 2002; 34: 1A pg 444. n=108 with hereditary or idiopathic pancreatitis. (28% had + fhx) 12 c PRSS1 mutation, 24 c SPINK1 (21 s fhx); 22 had + CFTR mutation.
-Pancreatology 2001; 1: 405-415. Consensus guidelines for testing for H. Pancreatitis. PRSS1 gene -cationic trypsinogen
- David Whitcomb’s laboratory at the University of Pittsburgh. The test is commercially available there. Their web site for the forms is:
- -JPGN 2011; 52: 262. Review.
- -J Pediatrics 2011; 158: 612. Acute pancreatitis can result in diabetes.
- -Clin Gastro & Hep 2010; 8: 410-416, 417. REVIEW of acute pancreatitis. Rec NJ generally over TPN.
- -Clin Gastro Hep 2010; 8: xxii. Anomalous pancreatobiliary jxn as a cause.
- -JPGN 2009; 49: 137. Pancreatitis assoc w celiac
- -Clin Gastro & Hep 2009; 7: 702. Harmless Acute pancreatitis score. Nonsevere when NL hgb, NL creatitine, and no rebound tenderness/guarding
- -Alim Pharm Ther 2008; 28: 777-781. Use of a low fat diet helped shorten hospital stay among adult pts with acute pancreatitis.
- -Clin Gastro & Hep 2008; 6: 1070, 1077. Fluids and imaging in acute pancreatitis. With imaging, CT probably best.
- – J Pediatrics 2008; 152: 106. Acute pancreatitis in young children
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