Snapshot A 10-year-old girl with a past medical history of epilepsy presents to the emergency room after sustaining a fall on the playground. She was fatigued and confused after the event and complained of pain in her wrist. On review of systems, she endorsed polyuria and polydipsia. Relevant medications included valproic acid, started 6 months ago, for her epilepsy. On physical exam, her right wrist was erythematous, swollen, and tender. Laboratory evaluation revealed hypokalemia, hypocalcemia, hypophosphatemia, and a mild metabolic acidosis. Introduction Clinical definition a type of renal tubular acidosis (type 2) in the proximal convoluted tubules (PCT) Epidemiology incidence hereditary forms occur in 1:40,000 demographics hereditary forms affect Caucasian children Etiology hereditary conditions cystinosis most common genetic cause Wilson disease tyrosinemia galactosemia multiple myeloma drugs cisplatin tenofovir valproic acid expired tetracyclines ifosfamide heavy metal poisonings Pathogenesis defect in PCT causes problems in reabsorption of almost all amino acids, glucose, bicarbonate, phosphate, and potassium this causes all of the above to be excreted in the urine excretion of bicarbonate causes a metabolic acidosis defect is due to direct injury to PCT in genetic cases there is often a defective enzyme in nutrient metabolism that causes damage to the PCT light chains form crystals in PCT, causing damage Associated conditions osteomalacia/rickets chronic ↓ phosphate and insufficient synthesis of vitamin D hypokalemia due to ↓ early Na+ reabsorption leading to ↑ K+ exchange Prognosis depends on etiology of Fanconi syndrome prognostic variable negative hereditary diseases Presentation Symptoms primary symptoms renal disease polyuria polydipsia bone disease bone pain in the backs and hips pathologic fractures constitutional myalgias weight loss fatigue hereditary abnormalities failure to thrive developmental delay Physical exam signs of rickets bowed legs scoliosis teeth abnormalities Studies Labs electrolyte panel hyponatremia hypokalemia hypocalcemia hypophosphatemia ↑ serum creatinine metabolic acidosis Urine studies aminoaciduria glycosuria phosphaturia urine pH < 5.5 defect in bicarbonate reabsorption leads to increased excretion of bicarbonate in urine urine is then acidified by the intercalated cells in collecting tubule Diagnostic criteria no specific criteria, but these findings could suggest Fanconi syndrome increased excretion of amino acids, phosphates, and bicarbonate in the urine metabolic acidosis Differential Distal renal tubular acidosis (type 1) urine pH > 5.5 Hyperkalemic renal tubular acidosis (type 4) hyperkalemia and urine pH < 5.5 Treatment Conservative supportive care with fluid and electrolyte repletion indications if any metabolic derangements are found especially if hypokalemia or hypophosphatemia are found Medical vitamin D (active form, cholecalciferol. or ergocalciferol) indications if osteomalacia is present bicarbonate indications metabolic acidosis Complications Bone disease (osteomalacia, osteopenia, and osteoporosis) Renal insufficiency