Cargando…

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

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, e...

Descripción completa

Detalles Bibliográficos
Autores principales: Gray Cater, Taylor Lauren, Borges Espinosa, Luis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10555376/
http://dx.doi.org/10.1210/jendso/bvad114.595
_version_ 1785116642763603968
author Gray Cater, Taylor Lauren
Borges Espinosa, Luis
author_facet Gray Cater, Taylor Lauren
Borges Espinosa, Luis
author_sort Gray Cater, Taylor Lauren
collection PubMed
description 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
format Online
Article
Text
id pubmed-10555376
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-105553762023-10-06 THU598 Pseudohypoaldosteronism Type 2: A New Variant Of A Rare Disease Gray Cater, Taylor Lauren Borges Espinosa, Luis J Endocr Soc Cardiovascular Endocrinology 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 Oxford University Press 2023-10-05 /pmc/articles/PMC10555376/ http://dx.doi.org/10.1210/jendso/bvad114.595 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Cardiovascular Endocrinology
Gray Cater, Taylor Lauren
Borges Espinosa, Luis
THU598 Pseudohypoaldosteronism Type 2: A New Variant Of A Rare Disease
title THU598 Pseudohypoaldosteronism Type 2: A New Variant Of A Rare Disease
title_full THU598 Pseudohypoaldosteronism Type 2: A New Variant Of A Rare Disease
title_fullStr THU598 Pseudohypoaldosteronism Type 2: A New Variant Of A Rare Disease
title_full_unstemmed THU598 Pseudohypoaldosteronism Type 2: A New Variant Of A Rare Disease
title_short THU598 Pseudohypoaldosteronism Type 2: A New Variant Of A Rare Disease
title_sort thu598 pseudohypoaldosteronism type 2: a new variant of a rare disease
topic Cardiovascular Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10555376/
http://dx.doi.org/10.1210/jendso/bvad114.595
work_keys_str_mv AT graycatertaylorlauren thu598pseudohypoaldosteronismtype2anewvariantofararedisease
AT borgesespinosaluis thu598pseudohypoaldosteronismtype2anewvariantofararedisease