Kidney Week

Abstract: FR-PO450

Late Presentation of Bartter Syndrome Type 2

Session Information

• Pediatric Nephrology - I
  November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1102 Genetic Diseases of the Kidneys: Non-Cystic

Authors

• Kaushal, Amit, University of Minnesota Division of Renal Diseases and Hypertension, Minneapolis, Minnesota, United States

Amit Kaushal,

• Lieske, John C., Mayo Clinic Minnesota, Rochester, Minnesota, United States

John C. Lieske,

• Harris, Peter C., Mayo Clinic Minnesota, Rochester, Minnesota, United States

Peter C. Harris,

• Elfering, Sarah L., University of Minnesota Division of Renal Diseases and Hypertension, Minneapolis, Minnesota, United States

Sarah L. Elfering,

Introduction

Bartter syndrome (BS) is an autosomal recessive disorder characterized by salt wasting that results from variants in at least 5 genes that encode proteins important for ion transport in the thick ascending loop of Henle (TALH). Features include polyuria, metabolic alkalosis, hypokalemia, and secondary hyperaldosteronism (often with low blood pressure, BP). Variants in the ROMK1 potassium channel gene (KCNJ1) cause BS2 which often results in severe clinical manifestations in infancy. Cases of BS2 diagnosed in adulthood have only infrequently been reported. Here we report a BS2 patient that presented in adulthood with hypokalemia, metabolic alkalosis and nephrocalcinosis.

Case Description

A 33-year-old male with no prior medical history presented with flank pain. Imaging showed no stone but instead bilateral nephrocalcinosis and hydronephrosis. He reported polydipsia (5-6 L daily) since childhood. Family history was pertinent for a brother with kidney stones, polydipsia and polyuria. On evaluation, BP was 131/91, potassium 2.7 mmol/L, bicarbonate 30 mmol/L, and calcium 8.5 mg/dl, creatinine 0.94 mg/dl and eGFR > 90ml/min. A 24-hour urine revealed high calcium (410 mg), low citrate (74 mg), high pH (6.9), and high volume (5 L). Urine potassium was inappropriately high given the hypokalemia (55 mmol). Genetic testing on a 102 candidate gene panel revealed 2 missense variants in KCNJ1, with one variant (c.949A>G; p.Lys317Glu) that has been associated with low BP but not described in BS2 to date and a second novel variant predicted to be pathogenic (c.949A>G; p.Lys336Glu). Oral potassium chloride was initiated and on follow-up serum potassium was 3.1 mmol/L. His brother with a similar phenotype had the same biallelic KCNJ1 changes.

Discussion

BS2 is caused by variants KCNJ1 gene that cause loss of ROMK function. Reduced ROMK activity impairs effective TALH function resulting in hypokalemia, salt wasting and volume depletion with subsequent activation of renin-aldosterone axis, and metabolic alkalosis. Generation of an effective TALH transepithelial electrochemical gradient is also essential for paracellular reabsorption of Ca²⁺ and Mg²⁺. Thus hypercalciuria, hypomagnesemia, and nephrocalcinosis are also frequently observed. Our case highlights that the diagnosis of BS should be considered beyond the neonatal period in patients who present with hypokalemia, hypercalciuria and nephrocalcinosis.