1. Etiology

• Fanconi syndrome is considered to represent the uniform response of the proximal renal tubules to various exogenous and endogenous insults that spare the glomeruli but result in a generalized pattern of tubular dysfunction
• types of insults:

  1. Primary Fanconi Syndrome

  1. Sporadic
  2. Hereditary

  • autosomal dominant
  • autosomal recessive
  • x-linked recessive

  2. Secondary Fanconi Syndrome

  1. Inborn Errors of Metabolism

  • Cystinosis
  • Galactosemia I & III
  • Glycogenosis - GSD Ia & XI
  • Hereditary Fructose Intolerance
  • Lowe Syndrome
  • Tyrosinemia I
  • Wilson Disease
  2. Acquired Diseases

  1. Proteinuric States

  • Multiple Myeloma
  • Nephrotic Syndrome

  2. Tubular Toxins

  • heavy metals (cadmium, lead, mercury)
  • drugs (outdated tetracycline, gentamicin, azathioprine)

  3. Others

  • Hyperparathyroidism (Primary & Secondary)
  • Interstitial Nephritis
  • Transplanted Kidney
  • Tumors
  • Vitamin D Dependant Rickets

2. Pathogenesis

• in the Primary form, there appears to be two pathophysiologic mechanisms:
  1. defective intracellular production or transfer of energy
  2. absence of proximal tubular brush borders (congenital defect in the biochemical synthesis of brush-border constituents)
• both mechanisms result in an impaired reabsorption of amino acids, bicarbonate, glucose, and phosphate
  • loss of HCO3 in the urine leads to a proximal RTA
  • renal K loss is secondary to the flooding of the distal tubule with HCO3 which stimulates sodium reabsorption in exchange for potassium leading to hypokalemia
  • contraction of the extracellular volume stimulates chloride reabsorption resulting in hyperchloremia and secretion of aldosterone leading to further potassium loss
  • phosphaturia -> hypophosphatemia + metabolic acidosis ->
    • rickets +/- osteomalacia
    • osteoporosis +/- pathological fractures
  • Vitamin D resistance may be due to impaired conversion of Vitamin D -> 1,25 (OH)2D3 by abnormal proximal tubular cells in the presence of metabolic acidosis

1. Primary Fanconi Syndrome

• episodes of vomiting, dehydration, weakness, & unexplained fever
• anorexia
• constipation
• polydipsia and polyuria (concentrating defect)
• failure to thrive and growth failure
• rickets

1. Serum

• normal anion gap hyperchloremic metabolic acidosis (with low serum bicarbonate)
• normal or low amino acids
• normal glucose
• hypophosphatemia, hypokalemia, hypouricemia
• elevated alkaline phosphatase

2. Urine

3. Imaging Studies

1. Primary Fanconi Syndrome

2. Secondary Fanconi Syndrome

• treat underlying disorder