Related Experiment Video
Updated: Mar 13, 2026
Functional Reconstitution and Channel Activity Measurements of Purified Wildtype and Mutant CFTR Protein
Published on: March 9, 2015
Hypochloremic Hypokalemic Metabolic Alkalosis as a Manifestation of CFTR-Related Disorder
Burcu Capraz Yavuz1, Deniz Dogru1, Birce Sunman1
1Department of Pediatric Pulmonology, Hacettepe University Faculty of Medicine, Ihsan Dogramaci Children's Hospital, Ankara, Türkiye.
Insights
Hypochloremic hypokalemic metabolic alkalosis (HHMA) is an early sign in children with cystic fibrosis (CF) and CFTR-related disorder. Early diagnosis and management, including salt supplementation, are vital for these patients.
Area of Science:
- Pediatric Endocrinology
- Genetics
- Metabolic Disorders
Background:
- Hypochloremic hypokalemic metabolic alkalosis (HHMA) can manifest in children with cystic fibrosis (CF) and CFTR-related disorder (CFTR-RD).
- Inadequate salt supplementation in diagnosed CF patients or presentation in unscreened/undiagnosed CF children can lead to HHMA.
- HHMA may also be a clinical sign in children with CFTR-RD who have normal or borderline sweat chloride test (SCT) levels.
Purpose of the Study:
- To compare the characteristics of children with CF (cwCF) and CFTR-RD who experienced HHMA.
- To analyze CFTR variant diversity in Türkiye within the context of HHMA episodes.
- To highlight the diagnostic and therapeutic challenges in managing these conditions.
Main Methods:
- A single-center retrospective study included children with CF and CFTR-RD who had at least one HHMA episode between January 2002 and August 2024.
- Demographic, genetic, clinical, and laboratory data were collected and compared between the two groups.
- Analysis focused on CFTR variant diversity in the Turkish population.
Main Results:
- 103 children (91 cwCF, 12 cwCFTR-RD) experienced 150 HHMA episodes.
- Median SCT levels were significantly lower in cwCFTR-RD (43 mmol/L) compared to cwCF (90 mmol/L).
- CF-related complications like diabetes, chronic Pseudomonas aeruginosa infection, and pancreatic insufficiency were exclusively observed in cwCF.
Conclusions:
- HHMA is a significant early clinical manifestation in both children with CF and CFTR-RD.
- Guidelines should better acknowledge HHMA as a manifestation of CFTR-RD to improve diagnosis and management.
- Salt supplementation, patient education, and long-term follow-up are crucial; diagnostic and therapeutic gaps persist, particularly regarding CFTR functional assays and modulator eligibility.
Background:
Hypochloremic hypokalemic metabolic alkalosis (HHMA) may occur in unscreened, undiagnosed, and unsupplemented children with cystic fibrosis (cwCF) or in diagnosed people with CF (pwCF) who are inadequately supplemented with salt. It may also present as a clinical manifestation in children with cystic fibrosis transmembrane conductance regulator-related disorder (cwCFTR-RD) who have borderline or normal sweat chloride test (SCT) levels.
Methods:
In this single-center retrospective study, we included cwCF and cwCFTR-RD who experienced at least one HHMA episode between January 2002 and August 2024. We compared the demographic, genetic, clinical, and laboratory characteristics of both groups within the context of the CFTR variant diversity observed in Türkiye.
Results:
A total of 103 children (91 cwCF, 12 cwCFTR-RD) were evaluated, comprising 150 HHMA episodes. Median SCT levels were significantly lower in cwCFTR-RD than in cwCF (43 [IQR, 34-53] vs. 90 [IQR, 75-99] mmol/L, p < 0.001). Variants such as F1052V, D1152H, and F200I were observed in 6 of 24 variants (25%) in cwCFTR-RD. CF-related complications including diabetes (15.3%), chronic Pseudomonas aeruginosa infection (18%), and pancreatic insufficiency (83%) occurred only in cwCF.
Conclusion:
HHMA represents an early and clinically significant manifestation in both cwCF and cwCFTR-RD. Clearer acknowledgment of HHMA as a manifestation of CFTR-RD within guidelines is crucial for improving diagnostic clarity and guiding appropriate management decisions. Salt supplementation, family education, and long-term follow-up are essential components of care for both groups. Furthermore, limited access to CFTR functional assays and the ineligibility of one-third of cwCF for current modulators together show the ongoing diagnostic and therapeutic gaps.
Related Concept Videos
01:23Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
01:29Roles of Electrolytes: Chloride and Bicarbonate
Conditions such as hypochloremia can arise from insufficient chloride reabsorption by the kidneys, often compounded by extended bouts of diarrhea, vomiting,...
01:29Disorders of Acid-Base Balance
Respiratory Acidosis and Alkalosis
Respiratory acidosis occurs due to an increase in the partial pressure of carbon dioxide PCO2 in the blood. It often arises from shallow breathing or impaired gas exchange caused by...
01:24Renal Tubule and Collecting Duct
Proximal Convoluted Tubule (PCT):
The PCT is the initial segment of the renal tubule, extending from the Bowman's capsule that encloses the glomerulus. Its convoluted structure and microvilli-lined cells increase the surface area for reabsorption. The PCT reabsorbs glucose, amino acids, sodium, and water from the filtrate, ensuring essential...
01:24Chronic Kidney Disease II: Clinical Manifestations
01:24Cystic Fibrosis: Management
Sinus disease and chronic...