Introduction: Hereditary Pancreatitis (HP) is a rare fibro-inflammatory genetic disease of the pancreas that follows a pathological pathway of recurrent pancreatitis precipitating cycles of inflammation and resolution, causing irreversible damage through fibrosis and pancreatic parenchymal loss, chronic abdominal pain, and dependency upon pain management opioids. HP symptoms typically present in children before the age of ten, and the condition is diagnosed by a genetic mutation panel inclusive of the following HP-associated genetic variants: serine protease 1 (PRSS1); serine protease inhibitor Kazal-type 1 (SPINK1), cystic fibrosis transmembrane conductance regulator (CFTR), chymotrypsin C (CTRC), A-type carboxypeptidase (CPA1), and calcium-sensing receptor (CASR). Severe HP are candidates for TPIAT. This project is the first to identify Australian families suffering from HP and assess correlation between phenotypic disease outcome and genotypic variant with the goal of establishing a comprehensive list of candidates for the TPIAT program within Australia.

Methods: HP patients from existing hospital records and interviews were administered to collect HP-associated data including pain management, medical prescriptions, interventions, smoking and alcohol history, and overall quality of life. Saliva biosamples were obtained for whole-exome-sequencing (WES). Genetic data were for variant discovery and correlation with HP phenotype.

Results: A total of 21 pedigrees comprising 155 individuals were recruited for the project. Overall, 76% of HP presented with clinical onset before the age of 10. Ongoing opioid usage for pain management in the HP cohort was 55% and 64% of patients reported ongoing moderate to severe pain. Strikingly, HP was 67 times more prevalent in Indigenous populations than non-Indigenous. Our estimated prevalence of HP in South Australia is much higher than the value of 0.1-0.3/100,000 previously described in European populations. Bioinformatics analyses of WES genotypic data yielded three potentially pathogenic variants identified outside of known HP-associated gene: ECE1, GJA5, and SPTBN5.

Conclusion: The percentage of HP patients requiring lifelong analgesics is alarming and genetic factors are an important cause of pancreatitis in Australian children. The study highlighted the importance of utilising genetic studies to guide medical decision-making in HP, and successfully established a patient database for candidates of TPIAT treatment.