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Updated: Dec 1 2021

Fanconi Syndrome

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  • Snapshot
    • An 18-year-old man with no significant past medical history presents with increased thirst and urinary frequency. Upon further questioning, the physician discovered that he recently decided on his own to take an old pack of tetracycline, prescribed 6 years ago, after he cut himself. Physical exam was unremarkable. Laboratory evaluation revealed hypokalemia and metabolic acidosis. Urine studies revealed glucosuria and phosphaturia.
  • Introduction
    • Clinical definition
      • a type of renal tubular acidosis (type 2) in the proximal convoluted tubules (PCT)
    • Associated conditions
      • osteomalacia/rickets
        • chronic ↓ phosphate and insufficient synthesis of vitamin D
      • hypokalemia
        • due to ↓ early Na+ reabsorption leading to ↑ K+ exchange
  • Epidemiology
    • Incidence
      • hereditary forms occur in 1:40,000
    • Demographics
      • hereditary forms affect Caucasian children
      • valproic acid-induced affects 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
  • 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
  • Imaging
    • Radiographs
      • indications
        • if bone disease is suspected
      • findings
        • pathological fractures
  • Studies
    • Labs
      • electrolyte panel
        • hyponatremia
        • hypokalemia
        • 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
  • Prognosis
    • Depends on etiology of Fanconi syndrome
    • Prognostic variable
      • negative
        • hereditary diseases
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