Genetic prevalence and characteristics in children with recurrent pancreatitis

J Pediatr Gastroenterol Nutr. 2012 May;54(5):645-50. doi: 10.1097/MPG.0b013e31823f0269.

Abstract

Aims: The causes of chronic (CP) and recurrent acute pancreatitis (RAP) in children include anatomic abnormalities and hereditary, metabolic, and autoimmune disorders, with a significant proportion of cases being labeled as idiopathic. Genetic pancreatitis (GP) is associated with mutations of cystic fibrosis transmembrane conductor regulator gene (CFTR), cationic trypsinogen (PRSS1) gene, and serine protease inhibitor Kazal type 1 (SPINK1). There literature is sparse regarding the clinical profile of GP in children. The aim of the present study was to estimate the prevalence and describe the clinical characteristics and outcome of genetic pancreatitis.

Methods: We reviewed the charts of children ages 18 years or younger with RAP or CP diagnosed from 2000 to 2009 at the Children's Hospital of Wisconsin, Milwaukee. Twenty-nine patients with RAP or CP were identified, of whom 23 (79%) were positive for mutations in ≥1 of the above-mentioned genes, and were included for review.

Results: The median age of symptom onset was 5 years (range 9 months-15 years) with diagnosis at 6.5 years (range 1-16 years). Twenty-one were white; 14 were girls. The most common presenting symptoms were abdominal pain and vomiting. Patients with RAP had 2 to 8 episodes of pancreatitis during 3.6-year average follow-up. Family history was positive in 5 of 29 of gene-tested patients. CFTR, SPINK1, or PRSS1 mutations were seen in 14 (48%), 8 (27%), and 7 (24%) patients, respectively. Two patients were homozygous for CFTR mutations, 6 heterozygote and 4 patients had 5 T variants. Two other patients had double heterozygous mutations in F508 del/2789 + 5G > A and F508 del/5T variant. Six patients with CP had a combination of CFTR and SPINK1 or PRSS1 mutations. Eleven of 29 (38%) patients met radiological criteria for CP. All of the heterozygote patients with a combination of CFTR and SPINK1 or PRSS1 mutations had CP. Eight patients developed a chronic pain syndrome and 2 developed exocrine pancreatic insufficiency during follow-up.

Conclusions: We found a high prevalence of genetic mutations in patients without anatomic or metabolic abnormalities known to be associated with pancreatitis. Studies are needed to ascertain the genetic causes of RAP and CP and examine the relation between single CFTR mutations and single mutations in the PRSS1 and SPINK1 genes.

MeSH terms

  • Acute Disease
  • Adolescent
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Child
  • Child, Preschool
  • Chronic Disease
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease*
  • Heterozygote
  • Humans
  • Infant
  • Male
  • Mutation
  • Pancreatitis / epidemiology*
  • Pancreatitis / genetics*
  • Pancreatitis / pathology*
  • Prevalence
  • Recurrence
  • Retrospective Studies
  • Trypsin / genetics
  • Trypsin / metabolism
  • Trypsin Inhibitor, Kazal Pancreatic
  • Wisconsin

Substances

  • CFTR protein, human
  • Carrier Proteins
  • SPINK1 protein, human
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Trypsin Inhibitor, Kazal Pancreatic
  • PRSS1 protein, human
  • Trypsin