Case report end-stage cystic fibrosis with fatal outcome in two siblings from a Chinese family: a 15-year diagnostic odyssey.

Background: Cystic fibrosis (CF) remains severely underdiagnosed in China due to the absence of newborn screening, limited sweat chloride testing capacity, and low clinical awareness. Diagnostic delay results in irreversible lung damage and precludes timely genotype-directed therapy. Case Presentation: A 16-year-old Chinese boy presented with end-stage CF lung disease after a 15-year diagnostic odyssey. He had recurrent lower respiratory tract infections since infancy, progressive bronchiectasis, CF-associated liver disease with portal hypertension, and chronic Conclusion: This family illustrates the convergence of three pharmacologically relevant barriers in underserved CF populations: prolonged diagnostic delay precluding specialized care, uncharacterized population-specific variants lacking theratyping data, and inaccessibility of CFTR modulators. The preserved pancreatic function despite end-stage lung disease is compatible with residual CFTR activity, but the contribution of either allele and potential responsiveness to CFTR modulators require transcript, protein, and functional characterization. This underscores the urgent need for systematic theratyping of under-characterized CFTR variants reported in East Asian populations. Expansion of sweat chloride testing, clinician education, and international collaborative theratyping efforts are needed to break this cycle.