What is the management of Fanconi syndrome?

Management of Fanconi Syndrome

The cornerstone of Fanconi syndrome management is aggressive fluid and electrolyte replacement combined with treatment of the underlying cause when identifiable, with specific disease-directed therapies for inherited forms like cystinosis requiring immediate cysteamine initiation. 1

Immediate Supportive Care

Fluid and Electrolyte Replacement

• Administer intravenous 10% dextrose/normal saline solutions at 1.5-2.0 times maintenance rate to maintain normoglycemia and prevent dehydration from sodium wasting. 1
• Provide phosphate supplementation to address hypophosphatemia and prevent progressive bone disease (rickets in children, osteomalacia in adults). 2
• Correct hypokalemia with potassium supplementation, which is often severe due to urinary losses exacerbated by metabolic acidosis. 2
• Administer bicarbonate supplementation to correct the type II renal tubular acidosis that characterizes this condition. 2

Disease-Specific Management

Cystinosis-Related Fanconi Syndrome

• Initiate cysteamine therapy immediately upon diagnosis confirmation at 1 mg/kg/day, escalating to 2 mg/kg/day if no improvement is observed. 1
• Implement nutritional management with restriction of phenylalanine and tyrosine intake, use medical foods devoid of these amino acids, and ensure protein intake higher than normal requirements. 1

Tyrosinemia Type I-Associated Fanconi Syndrome

• Start NTBC (nitisinone) treatment with dietary restriction of phenylalanine/tyrosine, which reverses or prevents tubulopathy in nearly all cases within weeks. 1
• Continue periodic screening for renal disease even after liver transplantation, as succinylacetone excretion persists post-transplant. 1

Acquired Forms (Adults)

• Conduct comprehensive medication and toxin review, as drugs, exogenous toxins, and heavy metals are the main causes in adults. 2, 3
• Discontinue offending agents immediately (including dietary supplements like red yeast rice, which can cause Fanconi syndrome). 4
• Perform serum and urine protein electrophoresis to screen for multiple myeloma with light chain deposition, the most common acquired cause in adults. 2

Fanconi Anemia-Related Manifestations

Hematologic Monitoring

• Obtain complete blood count at diagnosis with frequent ongoing monitoring. 1
• Perform bone marrow aspirate and biopsy at diagnosis and annually thereafter. 1

Cancer Surveillance

• Implement monthly oral self-examinations starting in early adolescence. 1
• Schedule biannual dental examinations. 1
• Arrange annual head and neck squamous cell carcinoma evaluation by otolaryngologist beginning in early adolescence. 1
• Conduct annual gynecologic examination starting in adolescence. 1
• Administer HPV vaccination per standard schedule. 1

Treatment of Bone Marrow Failure

• Consider androgen therapy, lower-dose hematopoietic stem cell transplantation regimens, and avoid DNA-damaging agents. 1

Ongoing Monitoring and Follow-up

Laboratory Assessment

• Regularly assess renal function through blood and urine tests including electrolytes, glucose, amino acids, and phosphate. 1
• Monitor serum creatinine and eGFR to track kidney function decline. 2
• Quantify proteinuria through albumin:creatinine ratio and protein:creatinine ratio. 2
• Check alkaline phosphatase levels, which are often elevated in rickets/osteomalacia from chronic phosphate wasting. 2

Imaging Studies

• Perform renal ultrasound to monitor kidney structure. 1
• Obtain bone X-rays and densitometry to assess for rachitic changes from hypophosphatemia. 1

Kidney Biopsy Indications

Perform kidney biopsy when Fanconi syndrome presents with hypouricemia, eGFR <60 mL/min/1.73m² with >2 mL/min/1.73m² per year decline, proteinuria with hematuria, or albumin:creatinine ratio >30 mg/mmol. 2

Genetic Testing

• Order genetic testing for inherited causes including cystinosis (CTNS gene), tyrosinemia type I, Fanconi anemia (multiple genes), and glycogen storage diseases when clinical presentation suggests hereditary etiology. 2

Critical Pitfalls to Avoid

• Do not overlook dietary supplements and non-prescription substances during history-taking, as these are increasingly recognized causes of acquired Fanconi syndrome. 4
• Do not delay cysteamine therapy in suspected cystinosis cases, as early treatment prevents irreversible complications. 1
• Do not assume liver transplantation cures tyrosinemia-related renal disease; continued monitoring is essential. 1