Abstract: TH-PO0407
Role of the FXYD2 Gene in Hypomagnesemia in Patients with 17q12 Deletion Syndrome
Session Information
- Fluid, Electrolyte, and Acid-Base Disorders: Clinical - 1
November 06, 2025 | Location: Exhibit Hall, 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
- Phiri, Thabiso Maseko, University System of Maryland, Baltimore, Maryland, United States
- Watnick, Terry J., University System of Maryland, Baltimore, Maryland, United States
- Al-Yousif, Yahya, University System of Maryland, Baltimore, Maryland, United States
Introduction
Patients with 17q12 deletion syndrome typically present in pediatric settings, exhibiting a range of congenital anomalies accompanied by electrolyte imbalances—most notably hypomagnesemia. Available literature is primarily based on individual case reports due to condition rarity. In this document, we present a specific case and detail the hypothesized mechanism as derived from the literature.
Case Description
A 22-year-old female presents with a medical history notable for short stature, intellectual delay, congenital esotropia, and a spontaneously closed ventricular septal defect (VSD). She also has a solitary right kidney with multiple cysts and chronic hypomagnesemia. The patient was referred to the adult nephrology clinic for evaluation of polycystic kidney disease (PKD) and hypomagnesemia. Prior microarray analysis identified a 17q12 deletion syndrome (1.274 Mb), which was felt to explain the patient's clinical features.
Her serum creatinine ranged between 0.88 to 0.92 mg/dl and magnesium 0.8 to 1.2. complete metabolic panel normal. Urine calcium to Creatinine ratio 0.02 and FEMg2+ documented as elevated Consistent with renal wasting. patient is chronically on magnesium oxide 800 mg to 1200 mg BID.
Discussion
The clinical presentation of patients with 17q12 deletion syndrome, including visual and heart defects, short stature, neurodevelopmental delays, and hypomagnesemia is well documented. This syndrome typically involves the loss of several genes, notably HNF1B, a transcription factor expressed in many tissues. HNF1B normally binds a conserved element in the FXYD2 promoter, driving the expression of FXYD2, which encodes the gamma subunit of the Na/K-ATPase. Since FXYD2 is predominantly expressed in the distal convoluted tubule (DCT) rather than the thick ascending limb (TAL), its loss disrupts Na/K-ATPase function. The reduced activity of this pump, essential for maintaining the sodium/potassium gradient, impairs several transporters such as NCC, KV1.1, TRPM6 (magnesium transporter), and SLC41A1. Unlike hypomagnesemia due to TAL dysfunction, which typically results in hypercalciuria, the DCT impairment leads to compensatory calcium reabsorption and, therefore, hypercalciuria, hypermagnesuria and hypomagnesemia are seen in 17q12 deletion syndrome. This case supports the hypothesis that FXYD2 dysregulation underlies the electrolyte imbalances observed.