Kidney Week

Abstract: FR-PO0910

A Hypokalemic Patient with Variants in Genes Encoding Epithelial Sodium Channel (ENaC) and Renal Outer Medullary Potassium Channel (ROMK)

Session Information

• Fluid, Electrolyte, and Acid-Base Disorders: Case Reports - 1
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Fluid, Electrolytes, and Acid-Base Disorders

• 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical

Authors

• Sweis, Nabil William, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Nabil William Sweis, MD

• Nieves Santiago, Richard Alexis, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Richard Alexis Nieves Santiago, MD

• Moorthi, Kmlst, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Kmlst Moorthi, MD, FASN

• Batlle, Daniel, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States

Daniel Batlle, MD

Introduction

The increasing use of multigene panel testing has given rise to instances where multiple genetic variants of varying pathogenicity and significance are simultaneously detected, complicating diagnostic interpretation. Here, we report a case harboring genetic variants for various renal transporters whose ultimate diagnosis was determined by the clinical phenotype.

Case Description

A 30-year-old man was referred for evaluation of childhood-onset hypokalemia, nephrocalcinosis, hypercalciuria and severe polyuria. He was normotensive. Family history was unremarkable. Labs demonstrated hypokalemic metabolic alkalosis, elevated plasma renin and aldosterone, and high Na, K and Ca excretion.
The patient was referred to us after genetic testing revealed a likely pathogenic c.363dup (p.Val122Cysfs*9) frameshift variant in SCNN1B (encoding ENaC), associated with type 1 pseudohypoaldosteronism. The genetic report also noted two heterozygous variants of uncertain significance in KCNJ1 (encoding ROMK) (c.581T>C [p.Phe194Ser] and c.124C>G [p.Leu42Val]), associated with Bartter type 2 syndrome.

Discussion

The SCNN1B variant reported as likely pathogenic is seen in type 1 pseudohypoaldosteronism, a syndrome characterized by Na wastage, volume depletion, hyperkalemia with metabolic acidosis, and high levels of plasma renin activity and aldosterone. Bartter type 2 results from loss-of-function mutations in the potassium channel ROMK, impairing potassium recycling in the thick ascending limb and thereby decreasing NKCC2-mediated Na, K, and Cl reabsorption. This also results in increased Na excretion with relative hypotension, and hypokalemic metabolic alkalosis. Despite the reported ROMK mutations being of uncertain significance, the clinical phenotype is consistent with Bartter type 2 syndrome, and therefore, is the correct diagnosis.
In conclusion, the newly found ROMK mutations (c.581T>C [p.Phe194Ser] and c.124C>G [p.Leu42Val]) matched the clinical phenotype and are therefore pathogenic while the SCNN1B mutation described as pathoegnic for type 1 pseudohypoaldosteronism was not contributing to the clinical phenotype. This case illustrates that when multiple genetic variants are detected in multigene panels, a focus on the clinical phenotype is critically important.