Abstract
Background
Genetic predisposition in paediatric idiopathic acute, acute recurrent pancreatitis
and its consequences are unknown. We studied frequency of genetic markers in acute,
acute recurrent, chronic pancreatitis and their impact on natural history.
Methods
Over a period of 2 years 68 consecutive children with pancreatitis (35.3% acute, 32.3%
acute recurrent, 32.3% chronic) and 25 controls were recruited in a single centre.
Common mutations for serine-protease-inhibitor (SPINK1 N34S), protease-inhibitor (PRSS1
R122H) and cystic fibrosis transmembrane conductance regulator (CFTR DeltaF508, 5T)
were analysed.
Results
Mean age was 13.4 ± 2.5 years. Overall, 30 cases (SPINK1 N34S n = 26, CFTR 5T n = 4) and 1 control (SPINK1 N34S) had mutations (p = 0.0001). The prevalence of SPINK1 N34S mutation was similar in chronic and acute recurrent
pancreatitis (45%). Six children with severe acute pancreatitis had SPINK1 N34S mutations
(25%, p < 0.05), and 4 were homozygous. On follow-up 5 acute pancreatitis patients with mutations
and 1 without mutations developed chronic pancreatitis (p = 0.004); 8 cases of acute recurrent pancreatitis progressed to chronic pancreatitis
(38%); of these 66.7% had mutations vs. 16.7% who did not (p = 0.03).
Conclusions
Almost 50% of idiopathic chronic, acute recurrent and 33% of acute pancreatitis in
children are genetically predisposed. Presence of genetic mutations in acute and recurrent
acute pancreatitis increases the risk of developing chronic pancreatitis.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Digestive and Liver DiseaseAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- The changing incidences of acute pancreatitis in children: a single-institution perspective.Journal of Pediatrics. 2002; 140: 622-624
- Changing incidence of acute pancreatitis: 10-year experience at the Royal Children's Hospital, Melbourne.Journal of Gastroenterology and Hepatology. 2007; 22: 1313-1316
- Increasing incidence of acute pancreatitis at an American pediatric tertiary care center: is greater awareness among physicians responsible.Pancreas. 2010; 39: 5-8
- Contrast and comparisons between childhood and adult onset acute pancreatitis.Pancreatology. 2013; 13: 429-435
- Management of childhood pancreatic disorders: a multidisciplinary approach.Journal of Pediatric Gastroenterology and Nutrition. 2003; 36: 206-212
- Pancreatitis in children.Journal of Pediatric Gastroenterology and Nutrition. 2003; 37: 591-595
- Acute pancreatitis in childhood: analysis of literature data.Journal of Clinical Gastroenterology. 2003; 37: 169-172
- Acute and recurrent pancreatitis in children: etiological factors.Acta Paediatrica. 2007; 96: 534-537
- Value of genetic testing in the management of pancreatitis.Gut. 2003; 53: 1710-1717
- Role of genetic disorders in acute recurrent pancreatitis.World Journal of Gastroenterology. 2008; 14: 1011-1015
- The course of genetically determined chronic pancreatitis.Journal of the Pancreas. 2003; 4: 146-154
- Genetic aspects of pancreatitis.Annual Review of Medicine. 2010; 61: 413-424
- SPINK1/PSTI polymorphism act as disease modifiers in familial and idiopathic chronic pancreatitis.Gastroenterology. 2000; 119: 615-623
- Tropical calcific pancreatitis: strong association with SPINK1 trypsin inhibitor mutations.Gastroenterology. 2002; 123: 1020-1025
- Absence of PRSS1 mutations and association of SPINK1 trypsin inhibitor mutations in hereditary and non-hereditary chronic pancreatitis.Gut. 2004; 53: 723-728
- Idiopathic chronic pancreatitis in India: phenotypic characterization and strong genetic susceptibility due to SPINK1 and CFTR gene mutations.Gut. 2010; 59: 800-807
- Mutations in the gene encoding the serine protease inhibitor, Kajal type 1 are associated with chronic pancreatitis.Nature Genetics. 2000; 25: 213-216
- Analysis of CFTR, SPINK1, PRSS1 and AAT mutations in children with acute or chronic pancreatitis.Journal of Pediatric Gastroenterology and Nutrition. 2006; 43: 299-306
- High incidence of PRSS1 and SPINK1 mutations in Korean children with acute recurrent and chronic pancreatitis.Journal of Pediatric Gastroenterology and Nutrition. 2011; 52: 478-481
- Screening of R1 22H and N29I mutations in the PRSS1 gene and N34S mutation in the SPINK1 gene in Mexican pediatric patients with acute and recurrent pancreatitis.Pancreas. 2012; 41: 707-711
- Definitions of pediatric pancreatitis and survey of present clinical practice.Journal of Pediatric Gastroenterology and Nutrition. 2012; 55: 261-265
- A clinically based classification system for acute pancreatitis. Summary of the International Symposium on Acute Pancreatitis, Atlanta, GA, September 11 through 13, 1992.Archives of Surgery. 1993; 128: 586-590
- Genetic mutation in a Spanish population with chronic pancreatitis.Pancreatology. 2009; 9: 644-651
- High frequency of N34H mutation in the SPINK1 gene in chronic pancreatitis detected by a new PCR-RFLP assay.American Journal of Medical Genetics. 2001; 100: 252-253
- Relation between mutation of cystic fibrosis gene and idiopathic pancreatitis.New England Journal of Medicine. 1998; 339: 653-658
- Frequency of the delta F508 mutation in 108 cystic fibrosis patients in Sao Paulo: comparison with reported Brazilian data.Clinics (Sao Paulo). 2005; 60: 131-134
- Mutations in the cystic fibrosis transmembrane regulator gene in patients with tropical calcific pancreatitis.American Journal of Gastroenterology. 2000; 95: 3658-3659
- Mutations of the cystic fibrosis gene in patients with chronic pancreatitis.New England Journal of Medicine. 1998; 339: 645-652
- CFTR, SPINK1, CTRC and PRSS1 variants in chronic pancreatitis: is the role of mutated CFTR overestimated.Gut. 2013; 62: 582-592
- The SPINK1 N34S variant is associated with acute pancreatitis.European Journal of Gastroenterology and Hepatology. 2008; 20: 726-731
- Pancreatic secretory trypsin inhibitor (SPINK1) gene mutation in patients with acute pancreatitis.Pancreas. 2005; 30: 239-242
- SPINK1 N34S is strongly associated with acute recurrent pancreatitis but is not a risk factor for the first or sentinel acute pancreatitis event.American Journal of Gastroenterology. 2010; 105: 446-451
Article info
Publication history
Published online: May 15, 2015
Accepted:
April 18,
2015
Received:
December 19,
2014
Identification
Copyright
© 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Inc. All rights reserved.