Hereditary pancreatitis syndromes commonly have an autosomal dominant inheritance.
Children present with recurrent episodes of abdominal pain caused by acute pancreatitis.
The pancreatitis becomes chronic.
With time, steatorrhoea and pancreatic calcification make the diagnosis simple.
Genetic defect was identified as a gain of function mutation in the cationic trypsinogen (PRSS1) gene that codes for the key pancreatic digestive enzyme, trypsin.
Chronic pancreatitis is also associated with loss of function gene mutations (1)
- examples include serine protease inhibitor Kazal-type 1 (SPINK1) and chymotrypsin C (CTRC) genes encoding for two different proteins that both inhibit trypsin activity
- physiologic importance of CFTR is that it is necessary for ductal ion and water secretion to carry digestive enzymes secreted by the acinar cells to the duodenum
- both gain of function and loss of function mutations lead to increased activation of trypsin - this emphasises the importance of trypsin in the pathogenesis of pancreatitis (1)
- mutations of PRSS1, SPINK1, and CTRC involve digestive enzymes in the acinar cell of the exocrine pancreas
- mutations in PRSS1, SPINK1 and cystic fibrosis transmembrane conductance regulator (CFTR) genes are also associated with a faster progression from acute pancreatitis to chronic pancreatitis (2)
- patients with hereditary pancreatitis are at increased risk of developing diabetes mellitus, exocrine pancreatic insufficiency, and pancreatic adenocarcinoma (2)
Reference:
- Hines O J, Pandol S J. Management of chronic pancreatitis BMJ 2024; 384 :e070920 doi:10.1136/bmj-2023-070920
- Panchoo AV, VanNess GH, Rivera-Rivera E, Laborda TJ. Hereditary pancreatitis: An updated review in pediatrics. World J Clin Pediatr. 2022 Jan 9;11(1):27-37.