What is the treatment for Fanconi syndrome?

Treatment of Fanconi Syndrome

The treatment of Fanconi syndrome requires addressing the underlying cause while providing supportive care through fluid and electrolyte replacement, with specific therapies determined by the etiology. 1

Underlying Cause Management

• For cystinosis-related Fanconi syndrome, initiate cysteamine therapy as soon as diagnosis is confirmed, starting at 1 mg/kg/day and potentially increasing to 2 mg/kg if no improvement is observed 1
• In tyrosinemia type I-associated Fanconi syndrome, NTBC (nitisinone) treatment with dietary restriction of phenylalanine/tyrosine is associated with reversal or prevention of tubulopathy in nearly all cases within weeks 2
• For medication-induced cases (e.g., tenofovir, valproic acid), discontinuation of the offending agent is crucial and can lead to substantial recovery of proximal tubule function, though this may take months 3, 4, 5
• In supplement-induced cases (e.g., red yeast rice), discontinuation of the supplement and sometimes corticosteroid therapy may improve renal function 6

Supportive Care

• Provide fluid replacement with intravenous 10% dextrose/normal saline solutions at 1.5-2.0 times maintenance rate to maintain normoglycemia 1
• Replace lost electrolytes, particularly:
  • Phosphate supplementation to treat hypophosphatemia and prevent bone demineralization 7, 4
  • Bicarbonate supplementation to correct metabolic acidosis (type II renal tubular acidosis) 7, 5
  • Potassium replacement for hypokalemia 7
  • Sodium supplementation if sodium wasting is present 7

Nutritional Management

• For patients with cystinosis-related Fanconi syndrome:
  • Restrict phenylalanine and tyrosine intake 1
  • Use medical foods devoid of phenylalanine and tyrosine 1
  • Ensure adequate protein intake (higher than normal requirements) 1

Monitoring and Follow-up

• Regular assessment of renal function through:
  • Blood: blood urea nitrogen, creatinine, electrolytes including bicarbonate, calcium, and phosphate 2
  • Urine: glucose, amino acids, calcium, phosphate, calcium-to-creatinine ratio, tubular reabsorption of phosphate, total protein and albumin 2
  • Renal ultrasound to monitor kidney structure 2
  • Bone X-rays and densitometry to assess for rachitic changes from hypophosphatemia 2

Special Considerations

• For tyrosinemia type I patients who have undergone liver transplantation, periodic screening for renal disease is recommended as SA (succinylacetone) excretion continues post-transplant 2
• In patients with Fanconi anemia-related manifestations, additional monitoring is required:
  • Hematologic monitoring with complete blood count and bone marrow evaluation 1
  • Cancer surveillance, including oral, dental, and head and neck examinations 1
  • Annual gynecologic examination starting in adolescence 1
  • HPV vaccination per standard schedule 1

Common Pitfalls and Caveats

• Standard renal function tests like estimated GFR and urine albumin/creatinine ratio are not sensitive markers of proximal tubule toxicity; more specific tests should be used for monitoring 4
• Diagnosis may be delayed due to vague symptoms, leading to unnecessary invasive investigations 3
• Recovery of proximal tubule function after withdrawal of toxic agents can take months, and chronic damage may persist in some cases 4
• For medication-induced cases, consider alternative therapies with less nephrotoxic potential (e.g., tenofovir alafenamide instead of tenofovir disoproxil fumarate for hepatitis B treatment) 3