Abstract Background Cystic fibrosis (CF) is a multisystem autosomal recessive disorder primarily affecting the respiratory, digestive, and reproductive systems. While commonly diagnosed in early childhood, late-onset presentations are increasingly recognized, especially in populations with non-classical or region-specific CFTR mutations. Case presentation We report a case of an 18-year-old Omani male with chronic sinusitis, productive cough, intermittent hemoptysis, and borderline sweat chloride levels. Radiographic imaging revealed extensive bilateral bronchiectasis, and genetic testing identified a homozygous CFTR c.575AT, p.(Asp192Val) mutation. Functional studies using patient-derived intestinal organoids demonstrated partial CFTR activity, with significant in vitro responsiveness to CFTR modulators. Trikafta improved chloride and bicarbonate transport by 80% and 170%, respectively, while a Vanzacaftor-based combination showed even greater efficacy. Discussion This case highlights the diagnostic challenges of adult-onset CF in non-Western populations and emphasizes the importance of genetic and organoid-based functional testing in confirming pathogenicity and guiding therapy. It also illustrates the growing role of precision medicine, particularly the potential benefit of CFTR modulators in rare genotypes not traditionally covered by current indications. Conclusion Recognizing atypical CF presentations and integrating advanced diagnostics are crucial for timely intervention. This case supports expanding access to genotype-specific therapies and organoid testing, particularly in regions with diverse CFTRmutation profiles. This abstract is funded by: Nil
Kashoub et al. (Fri,) studied this question.