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 Pathogenesis mutation involving NaCl cotransporter (NCTT) which results in impaired Na+ reabsorption in distal convoluted tubule Genetics inheritance pattern autosomal recessive mutations chromosome 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 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 epithelial Na+ 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 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