Background and Aims: Prevalence and natural history of hereditary pancreatitis (HP) remain poorly documented. The aims of this study were to assess genetic, epidemiological, clinical and morphological characteristics of HP in an extensive national survey.
Methods: A cohort comprising all HP pts was constituted by contacting all gastroenterologists and paediatricians (response rate: 84 %) and genetics laboratories (response rate: 100 %) in France (60.200.000 inhabitants). Inclusion criteria were the presence of PRSS1 gene mutation, or chronic pancreatitis in at least 2 first-degree relatives, or 3 second-degree relatives, in the absence of precipitating factors for pancreatitis.
Results: 78 families and 200 patients were included (181 alive, 6673 person-years, males: 53%, alcoholism: 5%, smoking: 34%). The prevalence was 0.3/100.000 inhabitants. PRSS1 mutations were detected in 68% (R122H: 78%, N29I: 12%, others: 10%). Penetrance was 93%. Median age at first symptom, diagnosis and date of last news, were 10 (range: 1-73), 19 (1-80) and 30 (1-84) years, respectively. HP was responsible for pancreatic pain (83%), acute pancreatitis (69%), pseudocysts (23%), cholestasis (3%), pancreatic calcifications (61%), exocrine pancreatic insufficiency (34%, median age of occurrence: 29 years), diabetes mellitus (26%, median age of occurrence: 38 years) and pancreatic adenocarcinoma (5%, median age: 55 years). No differences in clinical and morphological data according to genetic status were observed. 19 patients died, including 10 directly from HP (8 from pancreatic adenocarcinoma).
Conclusion: The prevalence of HP in France is at least 0.3/100 000. PRSS1 gene mutations are found in 2/3 with a 93% penetrance. Mutation type is not correlated with clinical/morphological expression. Pancreatic adenocarcinoma is the cause of nearly half of the deaths.