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Background <p>Liddle syndrome is a rare autosomal dominant form of monogenic hypertension caused by gain-of-function mutations in genes encoding the epithelial sodium channel (ENaC). The disease is characterized by early-onset hypertension, hypokalemia, metabolic alkalosis, and suppression of the renin–angiotensin–aldosterone system (RAAS). Early diagnosis is essential because targeted therapy with ENaC inhibitors can effectively control blood pressure and prevent end-organ damage, whereas mineralocorticoid receptor antagonists are ineffective.</p> Case presentation <p>We report a 15-year-old Chinese male who presented with severe hypertension (196/143 mmHg) and profound hypokalemia (1.73 mmol/L) with a history of hypertension since the age of 10 years. Laboratory evaluation revealed suppressed plasma renin concentration (3.157 pg/mL), relatively normal aldosterone (61.784 pg/mL), and an aldosterone-to-renin ratio of 19.57. Arterial blood gas analysis demonstrated metabolic alkalosis (pH 7.48, HCO₃⁻ 28 mmol/L). A 24-hour urinary potassium excretion of 81.65 mmol/day confirmed renal potassium wasting. Serum cortisol and ACTH were within normal limits. Although definitive biochemical exclusion of apparent mineralocorticoid excess (AME) and glucocorticoid-remediable aldosteronism (GRA) was not performed, no pathogenic variants were identified in <i>HSD11B2</i>, <i>CYP11B1</i>, or <i>CYP11B2</i> on the comprehensive genetic panel, providing molecular-level exclusion of these conditions. Echocardiography demonstrated ventricular wall thickening with mild valvular regurgitation. Brain MRI revealed bilateral basal ganglia and left corona radiata encephalomalacia with white-matter hyperintensity (Fazekas grade 1), indicating chronic hypertensive brain injury. Next-generation sequencing identified a heterozygous <i>SCNN1B</i> variant (NM_000336.3: c.1853&#xa0;C &gt; G; p.Pro618Arg; absent from gnomAD), classified as Likely Pathogenic per ACMG/AMP guidelines (criteria: PM1, PM2, PP3, PP4), confirming the diagnosis of Liddle syndrome. Treatment with compound amiloride tablets and potassium supplementation normalized serum potassium within 48&#xa0;h and significantly improved blood pressure. At one-month follow-up, blood pressure was well controlled at 130/80 mmHg. Long-term follow-up is ongoing to assess sustained blood pressure control and end-organ recovery.</p> Conclusion <p>Although <i>SCNN1B</i> p.Pro618Arg is a recognized pathogenic hotspot variant, this case highlights the severe phenotypic consequences of delayed diagnosis in adolescents, and demonstrates that early genetic diagnosis and targeted ENaC inhibitor therapy are achievable even in resource-limited rural clinical settings. Early recognition and targeted therapy with ENaC inhibitors are critical to prevent serious cardiovascular and cerebrovascular complications. Genetic testing is essential for definitive diagnosis, particularly in resource-limited settings where misdiagnosis as primary aldosteronism (PA) may lead to ineffective treatment.</p>

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Liddle syndrome caused by SCNN1B mutation presenting with severe early-onset hypertension and hypokalemia in an adolescent: a case report

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  • 发表日期：

    2026年7月9日

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  • Xiao Min,
  • Yuan Liang

摘要

Background

Liddle syndrome is a rare autosomal dominant form of monogenic hypertension caused by gain-of-function mutations in genes encoding the epithelial sodium channel (ENaC). The disease is characterized by early-onset hypertension, hypokalemia, metabolic alkalosis, and suppression of the renin–angiotensin–aldosterone system (RAAS). Early diagnosis is essential because targeted therapy with ENaC inhibitors can effectively control blood pressure and prevent end-organ damage, whereas mineralocorticoid receptor antagonists are ineffective.

Case presentation

We report a 15-year-old Chinese male who presented with severe hypertension (196/143 mmHg) and profound hypokalemia (1.73 mmol/L) with a history of hypertension since the age of 10 years. Laboratory evaluation revealed suppressed plasma renin concentration (3.157 pg/mL), relatively normal aldosterone (61.784 pg/mL), and an aldosterone-to-renin ratio of 19.57. Arterial blood gas analysis demonstrated metabolic alkalosis (pH 7.48, HCO₃⁻ 28 mmol/L). A 24-hour urinary potassium excretion of 81.65 mmol/day confirmed renal potassium wasting. Serum cortisol and ACTH were within normal limits. Although definitive biochemical exclusion of apparent mineralocorticoid excess (AME) and glucocorticoid-remediable aldosteronism (GRA) was not performed, no pathogenic variants were identified in HSD11B2, CYP11B1, or CYP11B2 on the comprehensive genetic panel, providing molecular-level exclusion of these conditions. Echocardiography demonstrated ventricular wall thickening with mild valvular regurgitation. Brain MRI revealed bilateral basal ganglia and left corona radiata encephalomalacia with white-matter hyperintensity (Fazekas grade 1), indicating chronic hypertensive brain injury. Next-generation sequencing identified a heterozygous SCNN1B variant (NM_000336.3: c.1853 C > G; p.Pro618Arg; absent from gnomAD), classified as Likely Pathogenic per ACMG/AMP guidelines (criteria: PM1, PM2, PP3, PP4), confirming the diagnosis of Liddle syndrome. Treatment with compound amiloride tablets and potassium supplementation normalized serum potassium within 48 h and significantly improved blood pressure. At one-month follow-up, blood pressure was well controlled at 130/80 mmHg. Long-term follow-up is ongoing to assess sustained blood pressure control and end-organ recovery.

Conclusion

Although SCNN1B p.Pro618Arg is a recognized pathogenic hotspot variant, this case highlights the severe phenotypic consequences of delayed diagnosis in adolescents, and demonstrates that early genetic diagnosis and targeted ENaC inhibitor therapy are achievable even in resource-limited rural clinical settings. Early recognition and targeted therapy with ENaC inhibitors are critical to prevent serious cardiovascular and cerebrovascular complications. Genetic testing is essential for definitive diagnosis, particularly in resource-limited settings where misdiagnosis as primary aldosteronism (PA) may lead to ineffective treatment.