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C. McCaul, K. Caulfield

Liddle’s syndrome

Liddle’s syndrome

Schlüsselwörter Liddle’s syndrome; ICD 10: I15.1; Pseudohyperaldosteronism
Keywords Liddle’s syndrome; ICD 10: I15.1; Pseudohyperaldosteronism
Zusammenfassung Dieser Beitrag enthält keine Zusammenfassung
Summary

In 1963, Dr. Grant Liddle, an endocrinologist in the United States, described this syndrome. It is a rare inherited disorder of sodium channels resulting in excessive salt reabsorption from the distal nephron [1]. Initial presentation has been described from infancy through to late adulthood and in some circumstances first presentation of genetically prone patients has been evident with pregnancy induced hypertension [2,3]. This renal tubular defect causes severe hypertension, hypokalaemia, metabolic alkalosis, decreased renin and angiotensin [2].  It is inherited as an autosomal dominant trait with variable penetrance. Complete linkage of the disorder is localized to gene 16p13-p12 or 16p12.2 [4].

These genetic defects either delete the C-terminus of β- or γ-ENaC or mutate a proline or a tyrosine within a short sequence, called the PY (Pro-Pro-x-Tyr) motif. This deletion/mutation of the PY motif in βENaC or γENaC impairs the ability of Nedd4-2 to bind (and thus ubiquitylate) ENaC, leading to accumulation of ENaC channels at the plasma membrane and increased channel activity. These alterations of the beta or gamma subunits of the epithelial sodium channel of the aldosterone sensitive distal nephron lead to increased sodium and water reabsorption owing to the resulting increase in transepithelial voltage [6]. Potassium and hydrogen ions are secreted into the collecting duct, resulting in hypokalaemic metabolic alkalosis. There have been only 30 cases of Liddle’s syndrome reported in English literature [2].

The clinical phenotype resembles primary hyperaldosteronism, and the presenting feature is typically hypertension in teenage years. Patients are often asymptomatic. Renal impairment may occur due to hypertension. Muscle weakness in combination with severe hypertension has been reported in elderly population with the syndrome [2]. The defining factor in the diagnosis is evidence of suppressed aldosterone levels, and the lack of response to treatment with the mineralocorticoid receptor blocker spironolactone [6;7]. Metabolic abnormalities can be corrected by dietary salt restriction, and administration of antagonists of the epithelial sodium channel such as amiloride or triamterene [8].  Renal transplantation has been used as treatment [9].

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