Hypochloremic Hypokalemic Metabolic Alkalosis as a Manifestation of CFTR-Related Disorder.

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.