Pseudo‐Bartter syndrome in Chinese children with cystic fibrosis: Clinical features and genotypic findings

Abstract Objectives To characterize the clinical and genotypic features of cystic fibrosis‐associated pseudo‐Bartter syndrome (CF‐PBS) in Chinese children. Methods We recruited and characterized the clinical manifestations of 12 Chinese children with CF‐PBS. Sweat test, blood and urinary analysis, sputum culture, chest and sinus computed tomography, and abdominal ultrasonography were obtained. Whole‐exome sequencing, bioinformatics analysis, and Sanger sequencing validation were performed to define the genotypes. Results CF‐PBS was accompanied by recurrent and/or persistent pneumonia (91.7%), pancreatitis (83.3%), vomiting and/or diarrhea (66.7%), failure to thrive and liver disease (58.3% respectively), among our patients. The predominant organisms found in the airways were Pseudomonas aeruginosa (83.3%) and Staphylococcus aureus (75.0%). The mean concentrations of blood gas and electrolytes were pH 7.58, bicarbonate 40.8 mmol/L, sodium 125.9 mmol/L, chloride 77.5 mmol/L, and potassium 2.6 mmol/L. A high recurrence rate (50.0%) of CF‐PBS was observed despite continued electrolyte supplementation during follow‐up. In all, 19 different variants of CFTR gene were identified, and 10 of these were found to be novel observations (c.262_266delTTATA[p.L88FfsX21], c.579+2insACAT, c.1210‐3C>G, c.1733T>C[p.L578P], c.2236_2246delGAGGCGATACTinsAAAAATC[p.E746KfsX8], c.3068T>G [p.I1023R], c.3635delT[p.V1212AfsX16], c.3859delG[p.G1287EfsX2], c.3964‐7A>G and ΔE23 [c.3718‐?_3873+?del]). The c.2909G>A[p.G970D] was the most common variant, with an allele frequency of 16.6%. A homozygous genotype of c.1521_1523delCTT[p.F508del] was discovered for the first time in patients of Chinese origin. Conclusions In China, CF‐PBS usually presents early and recurs frequently in infancy, accompanied by multiple comorbidities. Recurrence of CF‐PBS in school‐going patients does occur but is rare. The p.G970D is the most frequent variant, with a significant ethnic tendency of Chinese origin.