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 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.