Snapshot A 5-year-old boy is brought to the pediatrician for muscle aches and pains. He denies any recent trauma. On review of systems, he endorses increased thirst and increased urinary frequency. Laboratory exam reveals hypomagnesemia and normal potassium. His urine studies show decreased calcium. He is sent home on magnesium supplements and plans for future genetic testing. Introduction Clinical definition a renal tubular defect affecting the distal convoluted tubules characterized by mild hypokalemia mild metabolic alkalosis significant hypomagnesemia normal blood pressure Epidemiology Incidence rare 1:40,000 Demographics detected in young children but can be detected in adulthood Risk factors consanguinity Etiology Pathogenesis mutation involving NaCl cotransporter (NCTT) which results in impaired Na+ reabsorption in distal convoluted tubule Genetics inheritance pattern autosomal recessive mutations long arm chromosome 16, position 13 SLC12A3 gene Presentation Symptoms polyuria polydipsia muscle weakness or cramp fatigue paresthesias abdominal pain vomiting Physical exam growth is often normal but can be delayed Studies Labs hypokalemia (lower than in Bartter’s) hypomagnesemia metabolic alkalosis genetic testing most definitive diagnosis Urine studies ↓ Ca2+ Differential Bartter’s syndrome normal serum magnesium Renal Tubular DefectsCategoryFanconi SyndromeBartter SyndromeGitelman SyndromeLiddle SyndromeDefect localizationProximal tubuleThick ascending loop of HenleDistal convoluted tubuleCollecting tubuleEtiologyWilson diseaseTyrosinemiaCystinosisMultiple myelomaGalactosemiaMitochondrial myopathiesMedicationsaminoglycosidescisplatinifosfamidevalproic acidHeavy metalsmercuryleadAutosomal recessive mutation involving the NKCC2 cotransporterAutosomal recessive mutationinvolving the NaCl cotransporterAutosomal dominant mutation leading to increased activity of epithelial Na+ channel (ENaC)FindingsHypophosphatemiaAminoaciduriaRenal glucosuriaTubular proteinuriaProximal renal tubular acidosisHypokalemiaHypochloremiaMetabolic alkalosisNormotensionElevated plasma renin levelHypokalemiaHypochloremiaMetabolic alkalosisHypomagnesemiaHypocalciuriaNormotensionHypertensionHypokalemiaMetabolic alkalosis Treatment Conservative optimize electrolytes with diet or supplements indications those with hypokalemia or hypomagnesemia Medical nonsteroidal anti-inflammatory drugs (NSAIDs) indications for patients who require medical therapy beyond dietary supplements drugs indomethacin celecoxib potassium-sparing diuretics indications to treat hypokalemia and metabolic alkalosis drugs amiloride eplerenone Complications Cardiac arrhythmia due to hypomagnesemia and hypokalemia Chondrocalcinosis