Genetic predisposition and its impact on natural history of idiopathic acute and acute recurrent pancreatitis in children

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: Child; Genetics; Idiopathic; Pancreatitis; SPINK1.