When Standard Newborn Screening Isn't Enough: Diagnostic Challenges in the Age of Globalization

Cystic fibrosis (CF) newborn screening combines immunoreactive trypsin testing and targeted CFTR mutation panels. However, in Europe, most standard panels are designed primarily for common variants in Caucasian populations. We report a newborn, born in Spain from immigrant parents, with positive CF screening but initially normal genetic testing and borderline sweat chloride values. Full CFTR sequencing ultimately revealed a homozygous pathogenic variant (p.H609R), previously described in individuals of Ecuadorian-Andean ancestry. This case highlights the importance of clinical vigilance and comprehensive genetic analysis in increasingly diverse populations.