Abstract: PUB300
Answering the Call for Genetic Testing: Recurrent Hypomagnesemia Secondary to the Gitelman-Like ADTKD-HNF1
Session Information
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Yanik, Andrew, University of Utah Health, Salt Lake City, Utah, United States
- Moody, Taylor R., University of Utah Health, Salt Lake City, Utah, United States
- Cioletti, Anne, University of Utah Health, Salt Lake City, Utah, United States
- Gilligan, Sarah, University of Utah Health, Salt Lake City, Utah, United States
Introduction
Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a group of inherited kidney disorders characterized by early onset chronic kidney disease. Mutations to the transcription factor hepatocyte nuclear factor 1B (HNF1B) are associated with renal cysts, diabetes, and tubular dysfunction. We report the case of a patient with recurrent hypomagnesemia and hypokalemia secondary to HNF1B mutation.
Case Description
A 22-year-old female with history of non-diabetic gastroparesis requiring tube feeds and total parenteral nutrition was seen by nephrology for refractory hypomagnesemia and hypokalemia. Since early adolescence she had recurrent hypomagnesemia and hypokalemia as low as 0.9 and 2.4, respectively. She was managed with thrice daily oral magnesium and potassium and daily IV magnesium through indwelling catheters. Due to frequent hospital admissions for central line-associated bloodstream infections, her long-term IV access was discontinued. A formal workup for hypomagnesemia showed an elevated 24-hour urinary magnesium of 578 mg/d and an elevated fractional excretion of magnesium of 17% with serum magnesium of 1.1 mg/dL. Interestingly, her genetic testing years prior revealed no pathogenic mutations causing Gitelman syndrome but instead showed a heterozygous whole gene deletion of HNF1B. She is currently managed with magnesium oxide thrice daily, IV mag thrice weekly, and amiloride. She was recently started on SGLT2 inhibition with improvement in her magnesium levels.
Discussion
HNF1B is a transcription factor encoded by the HNF1B gene on chromosome 17q12, mutations in which can present as tubular dysfunction similar to Gitelman syndrome. HNF1B has downstream targets that regulate the Na-K-ATPase pump in the basolateral membrane of the distal convoluted tubule (DCT). Loss of HNF1B limits active transcellular magnesium reabsorption and disrupts potassium handling, resulting in hypomagnesemia and hypokalemia. Several case reports demonstrated improvement in hypomagnesemia in patients with HNFB1 mutation when SGLT2 inhibitors are used as treatment for associated diabetes, but to our knowledge they have not been used for this indication in a non-diabetic patient. This case demonstrates the value of genetic testing, gives insight into the presentation of ADTKD-HNF1B, and suggests yet another indication for SGLT2 inhibitors.