Genotype and phenotype correlations in patients with cystic fibrosis and pancreatitis.
OBJECTIVE
Pancreatitis is known to occur in some patients with cystic fibrosis (CF), but the prevalence, natural history, and genotypic basis are unclear. We examined a well-defined cohort of patients with CF to answer these questions.


METHODS
Patients with CF were identified from a computerized database (1966-1996). Chart audit identified all patients with CF and pancreatitis.


RESULTS
Among 1075 patients with CF, 937 (87%) were pancreatic insufficient at diagnosis, 28 (3%) were pancreatic sufficient but developed pancreatic insufficiency after diagnosis, and 110 (10%) have remained pancreatic sufficient. No patients with pancreatic insufficiency developed pancreatitis. Nineteen patients (17.3%) with pancreatic sufficiency experienced one or more attacks of pancreatitis. The mean age at diagnosis of pancreatitis was 22.7 +/- 10.3 years (range, 10-35 years), and pancreatitis was recognized before the diagnosis of CF in 6 patients (32%). The diagnosis of CF in pancreatic-sufficient patients, with and without pancreatitis, was established at a significantly older age than in those with pancreatic insufficiency (P < 0.0001). Genotyped patients with pancreatic insufficiency carried 2 severe mutant alleles. All genotyped patients with pancreatic sufficiency and pancreatitis carried at least one mild mutation. No specific genotype was predictive of pancreatitis.


CONCLUSIONS
Patients with CF with pancreatic sufficiency carry at least one mild mutant allele and are at a significant risk of developing pancreatitis. Symptoms of pancreatitis may precede the diagnosis of CF. Pancreatitis is associated with an otherwise mild CF phenotype.
Durno
Carol
C
Programmes in Integrative Biology, The Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
Corey
Mary
M
Zielenski
Julian
J
Tullis
Elizabeth
E
Tsui
Lap-Chee
LC
Durie
Peter
P
D000328:Adult; D000483:Alleles; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000150:complications* / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D016208:Databases, Factual; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D010195:Pancreatitis / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics* / Q000503:physiopathology; D010641:Phenotype; D015995:Prevalence; D011446:Prospective Studies
C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator