The course of genetically determined chronic pancreatitis.
BACKGROUND
The clinical course of chronic pancreatitis in patients with mutations of cationic trypsinogen and the trypsin inhibitor SPINK1 has not yet been characterized.


METHODS
Cationic trypsinogen (PRSS1) and the serine protease inhibitor, Kazal type 1 (SPINK1), were analyzed in patients with pancreatitis of unclear origin.


METHODS
Eighty subjects with trypsinogen mutations (21x N29I, 59x R122H) and 59 patients with the SPINK1 N34S variant (11 homozygous, 48 heterozygous) were included in the study.


METHODS
In patients with mutations of PRSS1 (N29I, R122H) and SPINK1 (N34S) the parameters such as calcification, dilatation of the main pancreatic duct, diabetes mellitus, hospital treatments, and surgery were recorded.


METHODS
Case control studies were performed to compare both mutational groups, and the follow-up time served as a matching criterion. The Kaplan-Meier analysis was used to estimate the time course of the symptoms.


RESULTS
Ten years after the onset of the disease, the probability (+/-SE) of symptoms in patients with PRSS1 mutations was as follows: 1st hospital stay: 86+/-4%; calcification: 21+/-4%; duct dilatation: 26+/-9%; surgery: 19+/-5%; diabetes: 6+/-5%. After 25 years, we found the following data: 1st hospital stay: 96+/-3%; calcification: 38+/-8%; duct dilatation: 38+/-8%; surgery: 37+/-10%; diabetes: 28+/-8%. A case-control-study of 38 pairs of patients with either PRSS1 or SPINK1 mutations showed that the probability of duct dilatation, diabetes and calcification was slightly higher in patients having a SPINK1 mutation. There was no difference between those subjects with a homozygous or heterozygous SPINK1 mutation. In comparison to alcoholic chronic pancreatitis patients, the PRSS1 associated disease revealed a lower frequency of calcification and diabetes.


CONCLUSIONS
The progression of chronic pancreatitis was slightly more rapid in patients with SPINK1 mutations than in patients with cationic trypsinogen mutations, but was much less than in those having alcoholic chronic pancreatitis.
Keim
Volker
V
Medizinische Klinik II, Universitätsklinikum Leipzig, Germany. keimv@medizin.uni-leipzig.de
Witt
Heiko
H
Bauer
Nadine
N
Bodeker
Hans
H
Rosendahl
Jonas
J
Teich
Niels
N
Mossner
Joachim
J
D016022:Case-Control Studies; D002648:Child; D002908:Chronic Disease; D018450:Disease Progression; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D010195:Pancreatitis / Q000175:diagnosis* / Q000235:genetics*; D014357:Trypsin; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000235:genetics*; D014362:Trypsinogen / Q000235:genetics*
D014359:Trypsin Inhibitor, Kazal Pancreatic; D014362:Trypsinogen; C489303:PRSS1 protein, human; D014357:Trypsin