🧬 Liddle's syndrome is a rare inherited cause of secondary hypertension. It presents with hypokalaemic hypertension, metabolic alkalosis, and suppressed renin + aldosterone levels — hence termed “pseudo-hyperaldosteronism”.

About 🔎

Liddle's syndrome: Autosomal dominant genetic disorder.
Mutation in the ENaC (Epithelial Sodium Channel) of the renal collecting ducts ➝ excessive sodium reabsorption ➝ hypertension.
Potassium wasting causes hypokalaemia, weakness, and arrhythmia risk.
Very rare but important to recognise in young patients with resistant hypertension.

Clinical Features 🧑‍⚕️

📈 Hypertension: Early onset, often severe.
💤 Weakness & Fatigue: From hypokalaemia.
⚡ Muscle cramps: Due to low potassium and metabolic alkalosis.
🌙 Nocturia & Polyuria: From impaired renal concentrating ability.
🫀 Arrhythmias: Severe hypokalaemia may trigger dangerous cardiac rhythms.

Investigations 🧪

🟢 Serum Potassium: Low (hypokalaemia).
🟢 ABG: Metabolic alkalosis.
🔻 Plasma Renin Activity: Suppressed.
🔻 Aldosterone: Suppressed (distinguishes from Conn’s syndrome).
🧬 Genetic Testing: Can confirm ENaC mutation.

Differential Diagnosis 🔍

Conn’s Syndrome (Primary Hyperaldosteronism): Both present with hypertension + hypokalaemia, but Conn’s has high aldosterone levels, while Liddle’s has low aldosterone.
Apparent Mineralocorticoid Excess (AME): Enzyme defect (11β-HSD2) or liquorice ingestion; also causes pseudo-hyperaldosteronism but via cortisol effect on mineralocorticoid receptors.

Management 💊

🥗 Low Sodium Diet: First-line to reduce hypertension.
💊 Amiloride or Triamterene: Block ENaC directly ➝ correct hypertension and hypokalaemia.
❌ Spironolactone ineffective: Because aldosterone is already low; mechanism is sodium channel mutation, not aldosterone excess.
👀 Lifelong treatment is usually required, with good prognosis if controlled.

Exam Clinical Pearl ✨

If you see a young patient with hypertension, hypokalaemia, metabolic alkalosis and low renin & aldosterone ➝ think Liddle’s syndrome. Treatment is with amiloride, not spironolactone.

Cases — Liddle’s Syndrome

Case 1 — Young-onset hypertension 🧑: A 19-year-old man is found to have BP 170/105 mmHg during a routine sports medical. Bloods: low potassium, metabolic alkalosis, suppressed renin and aldosterone. Family history: father with early stroke. Diagnosis: Liddle’s syndrome (ENaC overactivity causing pseudohyperaldosteronism). Managed with amiloride (ENaC blocker) and salt restriction.
Case 2 — Resistant hypertension 💊: A 24-year-old woman presents with persistent high BP despite triple therapy including ACE inhibitor, calcium-channel blocker, and thiazide. Labs: K⁺ 2.8 mmol/L, HCO₃⁻ 31 mmol/L, suppressed renin and aldosterone. Diagnosis: Liddle’s syndrome with resistant hypertension. Treated with triamterene/amiloride; spironolactone ineffective as aldosterone is suppressed.
Case 3 — Childhood presentation 👦: A 12-year-old boy is referred with growth retardation, polyuria, and muscle weakness. Exam: hypertension (150/95). Labs: hypokalaemia, metabolic alkalosis, low renin and aldosterone. Genetic testing confirms ENaC mutation. Diagnosis: paediatric Liddle’s syndrome. Managed with ENaC blockers and nephrology follow-up.

Teaching Point 🩺: Liddle’s syndrome is a rare autosomal dominant disorder causing constitutive activation of epithelial sodium channels (ENaC). This leads to sodium retention, hypertension, hypokalaemic metabolic alkalosis, suppressed renin and aldosterone. Key clue: it mimics hyperaldosteronism but does not respond to spironolactone — instead, amiloride/triamterene are effective.

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Liddle's syndrome