Snapshot A 3-year-old boy is brought to the pediatrician due poor growth and increased urinary frequency. According to the mother, the child appears to be very thirsty. He was born prematurely and the mother states she was found to have polyhydramnios on ultrasonograpahy while pregnant. Laboratory testing is significant for hypokalemia, hypochloremia, mild hypomagnesemia, and metabolic alkalosis. Introduction Clinical definition a renal tubular disorder characterized by hypokalemia hypochloremia metabolic alkalosis normotension elevated plasma renin level Epidemiology incidence rare precise incidence is unknown demographics neonatal cases login to view 1 more bullet classic cases login to view 1 more bullet no race or sex predilection risk factors family history Pathophysiology pathobiology mutation involving the Na+/K+/Cl- cotransporter (NKCC2) results in salt and water loss resulting in login to view 2 more bullets Genetics inheritance pattern autosomal recessive Prognosis can slowly progress to interstitial fibrosis resulting in chronic renal failure Presentation Symptoms failure to thrive increased thirst polyuria polydipsia vomiting Physical exam clinical volume depletion maternal polyhydramnios growth retardation Studies Labs ↑ plasma renin and aldosterone ↓ serum potassium and chloride ↑ urine prostaglandin E genetic testing Differential Diuretic abuse Gitleman syndrome Surreptitious vomiting Mineralocorticoid excess Cystic fibrosis 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 Na+Cl- cotransporter Autosomal dominant mutation leading to increased activity of epithelial sodium channel (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 nonsteroidal anti-inflammatory drugs (NSAIDs) indication login to view 1 more bullet drugs login to view 2 more bullets potassium-sparring diuretics indication login to view 1 more bullet drugs login to view 3 more bullets potassium and magnesium supplementation indication login to view 1 more bullet Complications Cardiac arrhythmia due to severe hypokalemia