P2.L237: Nasal Polyps Leading to Newly Diagnosed Cystic Fibrosis in an Adolescent

Introduction: Cystic Fibrosis (CF) is a genetic disorder characterized by various pathogenic mutations in the CFTR gene, typically detected by newborn screening. We present a case in which two rare CFTR mutations eluded routine newborn screening but were identified during the investigation of multiple nasal polyps, emphasizing the importance of remaining vigilant in the face of atypical clinical presentations.

Case Description: A previously healthy 14-year-old white adolescent presented with congestion refractory to conventional treatment. Physical exam revealed a large, right nasal polyp and left deviated septum. The adolescent was referred to ENT and started on dupilumab. After dupilumab failed to improve symptoms, a CT sinus without contrast revealed multiple sinonasal polyps involving the bilateral maxillary sinuses and nasal cavity prompting work up for CF. Newborn screening revealed an elevated immunoreactive trypsinogen (IRT) of 204.5 ng/mL with a subsequent reflex genetic panel being negative for common CF mutations, and therefore, sweat chloride testing was deferred at that time. Given the severity of nasal polyposis with history of an abnormal newborn screen, an expanded CF variant panel analysis was completed revealing two rare CFTR mutations, p.Ser492Phe and c.2490+1G>A. These have not been previously reported to be occurring simultaneously in one individual. Sweat chloride values of 76 mmol/L and 90 mmol/L on the right and left arms confirmed the diagnosis of CF. Consequentially, fecal elastase and pulmonary function testing were completed and found to be within normal limits. Nutritional status was normal and lab testing was otherwise unremarkable with only a mild vitamin D deficiency.

Discussion: The presence of nasal polyps in this case prompted a broader diagnostic workup, revealing two rare CFTR mutations. This case highlights the critical role of clinical vigilance beyond routine newborn screening in diagnosing CF, particularly when faced with atypical presentations such as nasal polyposis in the setting of an undetected genetic mutation on newborn screening. Some states advocate expanded CFTR gene analysis when IRT is ultra-high on newborn screening. That approach would have led to a diagnosis soon after birth for this adolescent.

Conclusion: The awareness that a negative newborn screen may miss some CF diagnoses underscores the need for a high index of suspicion and thorough evaluation in the presence of persistent or unusual symptoms, enabling timely diagnosis and intervention for improved patient outcomes.