Clinical study
Clinical characterization of patients with hereditary pancreatitis and mutations in the cationic trypsinogen gene

https://doi.org/10.1016/S0002-9343(01)00958-5Get rights and content

Abstract

Purpose

We determined the clinical manifestations of hereditary pancreatitis in nearly 30 families.

Patients and methods

The two trypsinogen mutations N29I and R122H were identified in a group of 550 patients with chronic pancreatitis of unclear origin. The following criteria were used to characterize the severity of chronic pancreatitis (one point each): calcifications, cysts, dilation of the pancreatic duct, diabetes, hospital treatment, and operation. Stages were defined as stage 0 (no points), stage 1 (one to two points), stage 2 (three to four points), and stage 3 (more than four points). Smoking and drinking habits were also recorded.

Results

Six families with the N29I mutation (25 subjects with the mutation) and 21 families with the R122H mutation (76 subjects with the mutation) were identified. The median ages for the onset of disease were 11 years in N29I and 10 years in R122H patients. The severity of chronic pancreatitis and symptoms were similar for both mutations. About 26% (n = 26) of the 101 subjects carrying a mutation were asymptomatic, and 42% (n = 42) had mild disease (stage 1). Twenty-nine percent (n = 29) had moderate disease (stage 2), and only 4% (n = 4) had severe disease (stage 3).

Conclusions

Symptoms of patients with the N29I or R122H trypsinogen mutation were generally similar. The majority of subjects with trypsinogen mutations had mild disease or was asymptomatic.

Section snippets

Nomenclature

There has been confusion concerning the nomenclature of the trypsinogen mutations because of the two different schemes (chymotrypsin and trypsin systems) in use. For clarity and in accordance with recent recommendations 22, 23, only the trypsin nomenclature is used. Thus, N21I is called N29I, and R117H is called R122H.

Laboratory techniques

We analyzed more than 550 blood samples that were sent to our referral center for analysis of cationic trypsinogen gene mutations in patients who had chronic pancreatitis of

Results

Of more than 550 patients with suspected hereditary pancreatitis, 6 with the N29I mutation and 21 with the R122H variant were identified. A family history of chronic pancreatitis was evident in all 27 patients. We received blood samples from 52 relatives of the N29I patients and from 96 relatives of the R122H patients. A complete set of clinical data was available from a total of 25 subjects with the N29I mutation and from 76 subjects with the R122H mutation who are included in this report.

Discussion

We evaluated the clinical characteristics of patients with hereditary pancreatitis associated with the two trypsinogen variants N29I and R122H, as well as those of their relatives. Our estimate of about a 78% penetrance is consistent with prior estimates of about 80% 1, 8. Most subjects with the mutations were asymptomatic or had mild disease, although the scoring system that we used for chronic pancreatitis has not been validated.

Based on the number of relatives or affected subjects, the R122H

Acknowledgements

We thank Susanne Kistner for her expert technical assistance. The help of the patients affected by the disease and their physicians are acknowledged. The following colleagues in Germany contributed to the study: R. Becker (Kempten), C. Behnen (Sögel), M. Bertele (München), R. Geyer (Rückersdorf), K. Jobke (Rückersdorf), S. Koletzko (München), E. Pahlov-Nejad (Emsbüren), H. J. Peters (Sögel), R. Renz (Weiden), and M. Rünzi (Essen).

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    Supported in part by Grant Ke 347/8-1 from the Deutsche Forschungsgemeinschaft.

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