title: The natural history of hereditary pancreatitis: a national series.
abstract: OBJECTIVE
  The 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 patients 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 mutation in the cationic trypsingen gene (PRSS1 gene), or chronic pancreatitis in at least two first-degree relatives, or three 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).
  
  
  CONCLUSIONS
  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 the deaths.
authors.affiliation: Pôle des Maladies de l'Appareil Digestif, Service de Gastroentérologie-Pancréatologie, APHP, Hôpital Beaujon, Clichy Cedex, France.
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authors.lastname: Rebours
authors.forename: M-C
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authors.lastname: Boutron-Ruault
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authors.lastname: Schnee
authors.forename: C
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authors.lastname: Férec
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authors.lastname: Le Maréchal
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authors.lastname: Hentic
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authors.lastname: Maire
authors.forename: P
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authors.lastname: Hammel
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authors.initials: P
authors.lastname: Ruszniewski
authors.forename: P
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authors.lastname: Lévy