PC2150: Pancreatitis Due to Novel Gene Mutation of Cystic Fibrosis Transmembrane Conductance Regulator Gene

Introduction: Cystic fibrosis is a genetic disorder most commonly seen in the Caucasian population with an incidence of approximately 1/2500. It is also a disease with a wide spectrum of presentation with two patients with the same diagnosis rarely displaying the same phenotype. This variation is largely due to various mutations in the CFTR gene. Here we discuss a patient with a novel CFTR mutation which resulted in a delayed presentation of cystic fibrosis.

Case Description: 35 year old Caucasian male presented to primary care clinic to establish care after being recently discharged from hospital for initial complaint of abdominal pain. During hospitalization, patient was found to have necrotizing pancreatitis for which partial pancreatectomy and Whipple procedure was performed. At that time etiology of acute pancreatitis was unknown as patient had never had prior episodes and denied any risk factors including alcohol abuse or abdominal trauma. Was found to have a 1st paternal cousin with a diagnosis of cystic fibrosis but otherwise no contributory family history. Was started on Creon and then discharged home. After this initial hospital admission, patient had further episodes of pancreatitis that required hospitalization. Evaluated by gastroenterology in the outpatient setting where multiple genetic labs including SPINK1, PRSS1, IgG4 and CFTR were drawn and sent. CFTR testing showed p.R74W, p.D1270N and p.V201M variants in the CFTR gene which were commented to be associated with “variable clinical phenotype.” Patient underwent sweat chloride testing with first test being “borderline” and repeat testing also with “borderline” result. Patient referred to pulmonology and genetics for further evaluation.

Discussion: Cystic fibrosis is a fairly common disorder and when diagnosed in childhood typically have symptoms such as meconium ileus, failure to thrive, frequent respiratory infections and/or pulmonary dysfunction. However, it is important to remember that while uncommon, cystic fibrosis can also present in adults. Typically, these patients have more atypical symptoms including frequent episodes of pancreatitis, diabetes mellitus or infertility. Thus it is important for clinicians to include genetic conditions such as cystic fibrosis in the differential for adult patients that present with these atypical symptoms.

Conclusion: Due to continued research, multiple genetic variants of the CFTR gene have been identified and their ability to cause a spectrum of disorder in relation to cystic fibrosis. Further research will need to be done to evaluate if the complex R74W;R1070W;D1270N mutation corresponds with other clinical presentations.