Fanconi Syndrome: Definition and Clinical Features
Fanconi syndrome is a generalized dysfunction of the proximal renal tubules characterized by impaired reabsorption of multiple substances, leading to excessive urinary excretion of glucose, phosphate, amino acids, bicarbonate, and other organic compounds. 1, 2
Pathophysiology
- Fanconi syndrome represents a global transport defect in the proximal tubules, resulting in failure to reabsorb various substances that are normally reclaimed in this segment of the nephron 3
- The syndrome can be inherited (primary) or acquired (secondary) from various causes including medications, toxins, and systemic diseases 4, 2
- The underlying mechanism involves disruption of sodium-dependent transport systems and/or impairment of endocytosis in proximal tubular cells 5
Characteristic Laboratory Findings
Serum Abnormalities
- Hypophosphatemia due to impaired phosphate reabsorption, which can lead to osteomalacia and bone pain 1
- Hypokalemia resulting from increased urinary potassium losses, often exacerbated by metabolic acidosis 1
- Normal anion gap metabolic acidosis due to bicarbonate wasting 4
Urinary Abnormalities
- Glucosuria despite normal serum glucose levels (normoglycemic glucosuria) 1, 2
- Generalized aminoaciduria with excessive excretion of amino acids 1, 3
- Phosphaturia leading to renal phosphate wasting 1, 2
- Elevated urinary pH (often above 5.5) despite systemic acidosis 1
- Increased excretion of uric acid, calcium, and low-molecular-weight proteins 3, 4
Clinical Manifestations
- Bone disease (rickets in children, osteomalacia in adults) due to phosphate wasting 6
- Muscle weakness and fatigue related to hypokalemia and metabolic acidosis 1
- Growth failure in children 6
- Polyuria and polydipsia 2
- Dehydration due to sodium wasting 2
Etiologies
Inherited Causes
- Cystinosis (most common cause in children) 2
- Tyrosinemia type I 6
- Glycogen storage diseases (e.g., Fanconi-Bickel syndrome due to GLUT2 deficiency) 6
- Wilson's disease 2
- Lowe syndrome 2
Acquired Causes
- Medications (e.g., certain antiretrovirals, chemotherapeutics, aminoglycosides) 3, 4
- Heavy metals and toxins (e.g., lead, cadmium, mercury) 7, 5
- Multiple myeloma with light chain deposition (most common cause in adults) 6
- Hematopoietic disorders like Fanconi anemia 6
- Kidney transplantation 6
Management
- Treatment of the underlying cause when possible 8, 2
- Supportive care with fluid and electrolyte replacement 8
- Phosphate supplementation to address hypophosphatemia 1, 8
- Potassium supplementation for hypokalemia 1
- Bicarbonate supplementation to correct metabolic acidosis 1, 8
- Disease-specific therapies (e.g., cysteamine for cystinosis) 8
Special Considerations
- In patients with Fanconi anemia, additional monitoring is required for bone marrow failure and increased cancer risk, particularly head and neck squamous cell carcinoma 6, 8
- Regular monitoring of electrolytes, renal function, and bone health is essential for all patients with Fanconi syndrome 8
- Early diagnosis and treatment are crucial to prevent complications such as growth failure and bone disease 6