Background and aims: 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). 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 the deaths.

Hereditary pancreatitis (HP) is an autosomal dominant disorder with incomplete penetrance characterized by recurring episodes of severe abdominal pain often presenting in childhood. Although this disorder has only been recently described, about 100 families have been documented worldwide. The pathophysiology of this disorder is unknown. Here, a large French family of 147 individuals (47 of whom were affected) from a four-generation kindred with HP has been examined and a genome segregation analysis of highly informative microsatellite markers has been performed. Linkage has been found between HP and six chromosome 7q markers. Maximal two point lod scores between HP and D7S 640, D7S 495, D7S 684, D7S 661, D7S 676 and D7S 688 were 4.00 (theta = 0.143), 5.85 (theta = 0.143), 4.91 (theta = 0.156), 8.58 (theta = 0.077), 8.28 (theta = 0.060), 4.40 (theta = 0.169), respectively. Multipoint linkage data combined with recombinant haplotype analysis indicated that the most likely order is: D7S 640-D7S 495-D7S 684-D7S 661-D7S 676-D7S 688, with the HP gene situated in the underlined region. As in all families reported in the literature, the clinical presentation of the disease is identical to the presentation of sporadic cases, one could expect that the knowledge of the HP gene could be a clue to pancreatitis in general. Based on its map position, this is the first step towards the positional cloning of the Hereditary Pancreatitis Gene (HPG).

Three dietary fibres with different physicochemical properties were studied in healthy humans for their effects on small intestinal motility and postprandial hyperglycaemia. Duodeno-jejunal motor activity was evaluated electromyographically for 180 min in six subjects who had ingested a test meal composed of glucose alone or glucose with 15 g of wheat bran (WB), sugar beet (SB) or ispaghula (I) fibres. Glucose and insulin concentrations were determined during the same period. Each subject received each of the four test meals randomly during a 4 d period. Addition of SB or I to the glucose meal altered duodeno-jejunal motility. Both of these fibres inhibited stationary contractile activity and increased the propagation length and velocity of propagated activity, whereas addition of WB had no effect. These results could reflect the high water-holding capacity of SB and 1. Blood glycaemic response to the glucose meal was reduced by SB and I but remained unchanged with WB. Postprandial blood glucose levels were significantly correlated with the total motility index (r 0·82) and stationary activity (r 0·79). Taken together, these observations suggest that the contractile activity induced by dietary fibre in the small intestine probably plays a major role in delayed glucose absorption.

Nearly one hundred families affected with hereditary chronic pancreatitis (HCP) have been reported in the literature. However, the fact that the disease involved only a few members of each family limits the informativeness of these reports and accounts for the infrequency and disappointing results of pathogenetic and genetic research. Our study concerned an exceptional HCP genealogy which would seem to provide an ideal model for the detection of a genetic anomaly linked to the expression of the disease. We studied 249 members of a family (214 still alive), covering eight generations born between 1800 and 1993. According to the customary criteria, 63 had definite and 17 probable HCP. Fifty-eight members under 18 years of age were still susceptible to developing the disease. This series confirms the mode of autosomal dominant heredity with variable penetrance. The clinical features and disease course were typical, except that symptoms tended to appear earlier. The series represents the most extensive HCP genealogy compiled and is one of the largest families studied in the field of genetic disease, regardless of etiology. Blood samples were taken from 146 subjects to facilitate pathogenetic and genetic research.