Snapshot A 3-year-old boy is brought to the pediatrician for a wellness visit. The mother reports that he has been sleeping and feeding well. She does not have any active concerns. Family history is significant for hypertension. His blood pressure is 110/90 mmHg. Laboratory testing is significant for hypokalemia and metabolic alkalosis. Introduction Clinical definition a renal tubular disorder affecting the collecting tubules characterized by hypertension hypokalemia metabolic alkalosis also known as pseudohyperaldosteronism Epidemiology incidence rare demographics young children suspected if there is early onset hypertension may not be detected until adulthood risk factors family history of early onset hypertension or hypokalemia may suggest Liddle’s Pathogenesis gain of function mutation involving the epithelial Na+ channel (ENaC) resulting in increased Na+ reabsorption in the collecting tubules this causes the lumen to be electronegative which causes a gradient that favors secretion of K+ into the lumen this results in decreased serum K+ mimics hyperaldosteronism recall that aldosterone increases the number of open luminal Na+ channels Genetics inheritance pattern autosomal dominant mutations chromosome 16p12 Prognosis very good with treatment Presentation Symptoms triad presenting at a young age hypertension hypokalemia metabolic alkalosis Physical exam hypertension Studies Labs hypokalemia metabolic alkalosis ↓ aldosterone ↓ renin genetic testing most definitive diagnosis Differential Primary hyperaldosteronism Congenital adrenal hyperplasia Renal Tubular Defects Category Fanconi Syndrome Bartter Syndrome Gitelman Syndrome Liddle Syndrome Defect localization Proximal tubule Thick ascending loop of Henle Distal convoluted tubule Collecting tubule Etiology Wilson disease Tyrosinemia Cystinosis Multiple myeloma Galactosemia Mitochondrial myopathies Medications aminoglycosides cisplatin ifosfamide valproic acid Heavy metals mercury lead Autosomal recessive mutation involving the NKCC2 cotransporter Autosomal recessive mutation involving the NaCl cotransporter Autosomal dominant mutation leading to increased activity of ENaC Findings Hypophosphatemia Aminoaciduria Renal glucosuria Tubular proteinuria Proximal renal tubular acidosis Hypokalemia Hypochloremia Metabolic alkalosis Normotension Elevated plasma renin level Hypokalemia Hypochloremia Metabolic alkalosis Hypomagnesemia Hypocalciuria Normotension Hypertension Hypokalemia Metabolic alkalosis Treatment Medical potassium-sparing diuretics indication for all patients with Liddle syndrome recall that these medications directly block Na+ channels in the collecting tubules drugs amiloride triamterene Complications Cardiac arrhythmia due to hypokalemia