P3C026: Keeping Clinical Curiosity Alive: Delayed Diagnosis of Ctfr-related Pancreatic Disease, a Case Report

Introduction: CFTR-related chronic pancreatitis is a rare, but increasingly diagnosed cause of chronic pancreatitis in both adults and adolescents. Delayed diagnosis carries deleterious consequences and chronic sequelae. Here with describe one such case.

Case Description: Our case focuses on a 28-year-old male who initially presented to establish care at the Internal Medicine-Pediatrics Clinic as a hospital follow-up for as episode of recurrent idiopathic pancreatitis. Physical exam was grossly unremarkable excepting for thin body habitus. He took no medications and abstained from alcohol. On systematic review, our patient endorsed chronic, foul-smelling diarrhea since adolescence. Starting in childhood, several admissions for pancreatitis found repeated negative workups by gastroenterology. In addition, he had been evaluated at age 17 by Pediatric Endocrinology for delayed puberty and short stature. Outside records revealed a bone age obtained during that time displaying diffuse osteoporosis when compared to age-matched peers. At the time, consultant notes explained this as ‘diagnostic error due to discrepancy in bone age versus chronologic age in the setting of delayed puberty’. Family history negative for genetic disorders, early onset osteoporosis, or pancreatitis. Recent labs indicated hypercalcemia, iron deficiency anemia, and vitamin D deficiency consistent with presumed exocrine pancreatic insufficiency and subsequent osteoporosis.
Piecing together this complicated clinical picture, we ultimately ordered genetic testing for heritable pancreatic diseases. This revealed a complex CFTR mutation associated solely with pancreatitis per the available literature. Our patient then started on pancreatic enzyme replacement. He went on to sustain a pathologic spiral tibial fracture from a ground level fall a year later.

Discussion: Overall, repeated misdiagnosis by several specialties spanning decades and developmental stages led to significant and potentially avoidable sequalae for our patient. In addition, it reminds us of the pitfalls of anchoring to prior diagnoses and to keep clinical curiosity alive when all the ‘pieces of the puzzle’ do not fit. The differential for chronic pancreatitis in the young adult population is relatively limited. Prior to the identification of causative genes, over 50% of chronic pancreatitis was deemed idiopathic. Exemplifying this, in a recent study when extensive sequencing of the CFTR gene was performed, 44% of patients previously diagnosed with idiopathic chronic pancreatitis were found to have at least one variant in the CFTR gene associated with CFTR dysfunction. Therefore, CFTR-related disease should always be considered even in the absence of pulmonary symptoms.

Conclusion: Our patient’s winding course to the final diagnosis of a CFTR-related disorder highlights the continued importance of a thorough history and continued questioning of prior diagnoses. With increasingly available and cost-effective genetic testing, we must reserve idiopathic chronic pancreatitis as a diagnosis of exclusion following these tests. Finally, this case beautifully illustrates the unique perspective and expertise an Internist-Pediatrician practicing primary care brings to the field of medicine.