Abstract: SA-PO206
Idiopathic Hypokalemia in a Patient With Autosomal Dominant Hypocalcemia (ADH) Type 2 With a GNA11 Point Mutation
Session Information
- Vascular Calcification, Nephrolithiasis, Bone
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: Bone and Mineral Metabolism
- 402 Bone and Mineral Metabolism: Clinical
Authors
- Silverberg, Rachael A., Madigan Army Medical Center, Tacoma, Washington, United States
- Khayat, Maurice I., Madigan Army Medical Center, Tacoma, Washington, United States
Introduction
Calcium-sensing receptors (CaSR) expressed on parathyroid and renal tubule cells contribute to calcium homeostasis through negative-feedback. Activating mutations of the CaSR or downstream signaling components may result in Autosomal Dominant Hypocalcemia (ADH) Types 1 and 2. These rare disorders are characterized by hypocalcemia, hyperphosphatemia, and low PTH. While hypokalemia and metabolic alkalosis are reported among patients with ADH Type 1, this is not well established in ADH Type 2.
Case Description
A 22-year-old male presented with headaches, irritability, lethargy, perioral paresthesia, muscle and facial spasms progressive over several years with recurrent evaluations in the Emergency Department. Serial labs revealed hypocalcemia, hyperphosphatemia, and low iPTH as well as hypokalemia, hypomagnesemia, and metabolic alkalosis. Treatment comprised oral calcitriol and daily supplementation with calcium citrate, cholecalciferol, potassium chloride, and magnesium citrate. Genetic testing revealed a heterozygous likely pathogenic variant in the GNA11 gene (c.178C>T) associated with ADH Type 2. Testing for Gitelman Syndrome, ADH Type 1, and 22q11.2 deletion were negative. Despite daily supplementation and a high potassium diet, he reported continued symptomatic episodes of hypokalemia characterized by palpitations, headaches, nausea, and irritability. His aldosterone and plasma renin activity were within normal limits. A 24-hour urine study showed high renal excretion of potassium, calcium, and phosphorus.
Discussion
ADH type 2 results from a gain-of-function mutation in the GNA11 gene encoding a G-protein in the CaSR signaling pathway. Increased activation of this pathway reduces calcium reabsorption in the renal tubule and inhibits PTH synthesis and secretion. Hypokalemia from a Barrter’s like syndrome has been reported in ADH Type 1 suspected from an inhibitory effect of the CaSR on the sodium-potassium-chloride (NKCC2) cotransporter. To our knowledge this is the first described case of hypokalemia in ADH type 2. While it may be due to similar downstream constitutive activation of the CaSR signaling pathway, his normal aldosterone and renin activity may suggest an alternative etiology.
The views expressed above are those of the authors and do not reflect the official policy of the Army, Department of Defense, or US Government.