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255 DILEMMA OF CF DIAGNOSIS - ACUTE RECURRENT PANCREATITIS IN A PATIENT WITH 2 CFTR GENE ALTERATIONS T Gonska, L Ellis, S Martin, J Zielenski, M Solomon, P Durie INTRODUCTION: About 20% of patients with Cystic fibrosis (CF) and preserved pancreatic function develop acute recurrent pancreatitis or chronic pancreatitis. On the other hand, it is often not possible to definitively establish or exclude a diagnosis of CF disease in patients presenting with pancreatitis who may also have alterations in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene. To illustrate this dilemma, we describe the case of a 15 year old female.
The Hospital for Sick Children, Toronto, Ontario
CASE REPORT: The patient had 2 episodes of acute pancreatitis at the age of 5 and 11 years. Clinically, there were no signs of malabsorption and normal fecal elastase concentration confirmed pancreatic sufficiency. Imaging of the pancreatic duct by ERCP after the last episode of pain was indicative for pancreas divisum.
DIAGNOSTIC TESTING FOR CF: Repeated sweat tests demonstrated normal results with sweat chloride concentrations of 18, 23 and 30 mmol/l. CFTR-mediated potential difference measurements at the nasal mucosa showed intermediate values between those of healthy controls and those of CF patients. Extensive genotyping identified 2 alterations in the CFTR gene (M348K and 5T).
DISCUSSION: Diagnosis of CF disease could not be confirmed for the following reasons. Repeated sweat tests were normal, but this can also occur in non-classic CF patients. CFTR-mediated potential difference was reduced, but reference limits for CF disease have not been clearly defined. Over 1400 CFTR mutations have been identified of which only a few have been proven to be CF disease-causing. Thus, the presence of rare mutations does not necessarily confirm a CF diagnosis, as seen in our case. However, the 5T alteration has been found in higher frequency in patients with idiopathic pancreatitis.
Though the defined criteria for CF diagnosis were not met, the presence of 2 CFTR mutations may reduce pancreatic fluid flow and cause ductal plugging. In combination with a ductal anomaly, this may increase the susceptibility of this highly vulnerable organ to develop pancreatitis. Such a "two hit hypothesis" has been suggested by Gelrud et al (Am J Gastroenterol 2004;99:1557-1562) as an explanation for the fact that only a subset of patients with pancreas divisum develop pancreatitis.