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Pseudo-Bartter Syndrome in Chinese Children with Cystic Fibrosis: Clinical Features and Genotypic Findings
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  • Yuelin Shen,
  • xiaolei tang,
  • Jinrong Liu,
  • Shunying Zhao
Yuelin Shen
Beijing Children's Hospital
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xiaolei tang
Beijing Children's Hospital
Author Profile
Jinrong Liu
Beijing Children's Hospital
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Shunying Zhao
Beijing Children's Hospital
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Peer review status:UNDER REVIEW

14 May 2020Submitted to Pediatric Pulmonology
15 May 2020Submission Checks Completed
15 May 2020Assigned to Editor
19 May 2020Reviewer(s) Assigned
08 Jun 2020Review(s) Completed, Editorial Evaluation Pending
09 Jun 2020Editorial Decision: Revise Major
05 Jul 20201st Revision Received
06 Jul 2020Submission Checks Completed
06 Jul 2020Assigned to Editor
06 Jul 2020Reviewer(s) Assigned

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 11 Chinese children with CF-PBS. Sweat test, blood and urinary analysis, sputum culture, chest and sinus computed tomography, abdominal ultrasonography were obtained. Whole-exome sequencing, bioinformatics analysis, and sanger sequencing validation was performed to define the genotypes. Results: CF-PBS was accompanied by recurrent and/or persistent pneumonia (100%), pancreatitis (81.8%), vomit and/or diarrhea (63.6%), failure to thrive (FTT) (63.6%) and liver disease (54.5%) among our patients. The predominant organisms found in the airways was Pseudomonas aeruginosa (90.9%) and Staphylococcus aureus (81.8%). The mean concentration of blood gas and electrolytes were: PH 7.58, bicarbonate 40.8 mmol/L, sodium 126.7 mmol/L, chloride 80.0 mmol/L, and potassium 2.7 mmol/L, respectively. A high recurrence rate (54.5%) of PBS was observed despite continued electrolyte supplementation during follow up. 17 different mutations of CFTR gene were identified, and 9 of them turned out to be novel observations (c.262_266delTTATA, c.579+2insACAT, c.1210-3C>G, c.1733T>C, c.2236_2246delGAGGCGATACTinsAAAAATC, c.3635delT, c.3859delG, c.3964-7A>G and ΔE23 [c.3718-?_3873+?del]). The c.2909G>A/p.G970D was the most common mutation, with an allele frequency of 18.2%. c.1521_1523delCTT/p.F508del was the first time found with homozygous genotype in patients of Chinese origin. Conclusions: In China, CF-PBS always occurs early and repeatedly in infancy, accompanied by the high frequency of multi-system co-morbidities. Recurring in school-age patients is rare but does exist. The c.2909G>A/p.G970D is the most frequent mutation in Chinese patients with CF-PBS, showing a significant ethnic tendency of Chinese origin.