Non pathological sweat test, pancreatic insufficiency and Cystic Fibrosis: an unusual case in a child with F508del-duplication of exons 1-3 CFTR genotype

• Published in: BMC pediatrics 2024-11, Vol.24 (1), p.752-6, Article 752
• Main Authors: Terlizzi, Vito, Fevola, Cristina, Castaldo, Alice, Vespa, Selene Del, Dolce, Daniela, Scarallo, Luca, Kleinfelder, Karina, Melotti, Paola, Sorio, Claudio, Taccetti, Giovanni, Lionetti, Paolo
• Format: Article
• Language: English
• Subjects: Aminophenols - therapeutic use; Case Report; CFTR; Child; Cystic fibrosis; Cystic Fibrosis - genetics; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Diagnosis; Drug Combinations; Drug therapy; Duplication; Exocrine Pancreatic Insufficiency - diagnosis; Exocrine Pancreatic Insufficiency - genetics; Exons - genetics; Female; Fibrosis; Gene mutations; Genetic aspects; Genotype; Health aspects; Humans; Ivacaftor; Male; Normal; Pancreatic diseases; Pancreatic insufficiency; Pediatric research; Physiological aspects; Risk factors; Sweat - chemistry; Sweat chloride
• ISSN: 1471-2431; 1471-2431
• DOI: 10.1186/s12887-024-05154-7

While Cystic Fibrosis is characterized by a high phenotypic variability, a correlation is reported between the pancreatic status and the CFTR genotype. Here we report an unusual case of a child with Cystic Fibrosis (F508del-duplication of exons 1-3 genotype) diagnosed at 8 years old for pancreatic insufficiency and non-pathological sweat test, in absence of respiratory symptoms and acute episodes of pancreatitis. Nasal potential differences and intestinal current measurements were normal, while the short-circuit current measured on patient-derived colonoids grown on Transwell indicated the presence of a reduced CFTR-dependent current relative to non-CF colonoids with, a modest improvement of CFTR activity record following treatment with elexacaftor/tezacaftor/ivacaftor.This case opens the discussion on the importance of performing CFTR sequencing and the search for large gene rearrangements in cases of pancreatic insufficiency of unclear etiology, also in the presence of non-pathological sweat test. Children with CF and non-pathological sweat chloride are likely to develop higher concentrations if they truly have CF.