6568 A Novel Case of Liddle Syndrome in Siblings: Insights into a Rare Genetic Mutation

Abstract

Abstract Disclosure: A.B. Humrickhouse: None. M. Peltsverger: None. Introduction: Liddle syndrome (LS) is an inherited form of hypertension caused by a mutation in the epithelialsodium channel (ENaC). This condition is characterized by hypertension (HTN), hypokalemia,hyporeninemia, and metabolic alkalosis, although clinical presentation can vary. Asymptomaticearly-onset HTN is common, and if left undiagnosed, it can lead to advanced renal disease,cardiovascular complications, stroke, and even sudden death. Treatment typically involves theadministration of ENaC blockers such as amiloride and triamterene. We present a novel case ofLS in two siblings resulting from a missense mutation in the SCNN1B gene. Case Presentation: The patient is a 24-year-old Hispanic female who presented for evaluation of poorly controlledHTN and severe hypokalemia of 2.9 mmol/L during the first trimester of pregnancy. She wasdiagnosed with HTN at age eighteen. The family history was notable for resistant HTN in herfather and younger brother. Biochemical evaluation revealed normal plasma-free metanephrinesand 24-hour urine-free cortisol. Low plasma renin activity (0.530 ng/mL/hr) and aldosterone(<1.0 ng/dL) were detected on multiple tests. The urine-free cortisol-to-cortisone ratio was <0.5,excluding the diagnosis of apparent mineralocorticoid excess syndrome. The diagnosis of LS wasconfirmed by genetic analysis, which identified a novel heterozygous mutation, c.1859 A>G(Tyr620Cys), in the SCNN1B gene, which had not been reported in the literature to date. Thesame mutation was identified in her brother. The patient was treated with a high dose ofamiloride (15 mg daily), which controlled her HTN and hypokalemia throughout her pregnancy. Discussion: LS is an autosomal dominant disorder with genetic heterogeneity. It is characterized by HTN,low plasma aldosterone and renin activity, and increased potassium excretion. This leads tohypokalemia and metabolic alkalosis. LS is caused by germline mutations found in theSCNN1A, SCNN1B, and SCNN1G genes, which encode the alpha, beta, and gamma subunits ofthe ENaC channel. These mutations lead to enhanced sodium reabsorption in the kidneys,independent of aldosterone. Our patient was diagnosed with hypertension at the age of 18.However, the diagnosis of LS was not made until six years later when she presented during herfirst trimester of pregnancy. Treatment with amiloride effectively controlled her hypertension andhypokalemia, which allowed her to deliver a healthy child. Amiloride was also prescribed for thepatient's brother. A combination of biochemical analysis and genetic testing enables a betterunderstanding of the various clinical presentations, ensuring appropriate treatment andprevention of end-organ damage. Genetic counseling is essential for families affected by LS. Presentation: 6/1/2024