THU598 Pseudohypoaldosteronism Type 2: A New Variant Of A Rare Disease

Abstract

Abstract Disclosure: T.L. Cater: None. L. Borges Espinosa: None. Introduction: Familial hyperkalemia and hypertension syndrome or pseudohypoaldosteronism type 2 (PH2) is a rare monogenic hypertension resulting from WNK1, WNK4, KLHL3, or CUL3 gene mutation. Subsequent interference at the Na-Cl co-symporter, epithelial Na, or ROMK channel results in metabolic acidosis, hyperkalemia, and hypertension responsive to thiazide treatment. This case demonstrates PH2 resulting from a KLHL3 gene variant not previously described. Mutations to KLHL3 decrease Na-Cl cotransporter expression in the distal convoluted tubule leading to increased sodium and chloride reabsorption, volume expansion, hypertension, and, therefore, less sodium available for potassium exchange in the collecting duct. Case Description: A 30-year-old female G1P0 with twin gestation was admitted at 33 weeks for preeclampsia with severe features. PMH was unremarkable. She underwent C-section and was discharged home with healthy twin daughters. BMP during admission showed hyperkalemia with peak potassium 5.2 mmol/L which improved to 4.6 mmol/L by discharge. Essential hypertension was diagnosed 3 months later (BP 130/90, 78 bpm, RR 16, BMI 30.0 kg/m2). Labetalol 50 mg BID was initiated. BMP obtained showed hyperkalemia as high as 6.4 mmol/L. Further workup showed undetectable renin with normal aldosterone, hyperchloremic metabolic acidosis with chloride 111 mmol/L and bicarbonate 20 mmol/L, and normal EKG. She was managed in the ED where her potassium improved to 5.1 mmol/L with persistent hyperchloremic metabolic acidosis. A diagnosis of pseudohyperkalemia was presumed initially. Labetalol was discontinued in favor of hydrochlorothiazide 12.5 mg daily. Lost to follow-up, she presented 10 years later to Endocrinology at age 41 for chronic hyperkalemia and hyperchloremic metabolic acidosis. Labs showed potassium 6.5 mmol/L, chloride 108 mmol/L, and bicarbonate 23 mmol/L. Exam showed BP 133/98, BMI 26.63 kg/m2. She recounted several ER visits over the past decade for hyperkalemia with highest reported potassium of 7.8. She had stopped her thiazide due to dizziness, palpitations, and fatigue. Family history was now notable for hyperkalemia in her father, two brothers, and fraternal niece but no genetic testing was available. We resumed hydrochlorothiazide 12.5 mg every other day; follow-up labs showed improved potassium 5.2 mmol/L. Genetic testing revealed heterozygosity in the KLHL3 gene for the c.1064T &gt G sequence, a variant that has not been reported in the literature or large population database. Conclusion: Hypertension in PH2, distinct in its presentation with hyperkalemia and metabolic acidosis, requires a detailed family history and hormonal evaluation to make the diagnosis. Genetic testing in our case patient revealed a variant at the KLHL3 gene not previously described, underscoring the utility of genetic testing in understanding this rare condition. Presentation: Thursday, June 15, 2023