Fanconi's syndrome

Fanconi's Syndrome

Fanconi's syndrome is a rare disorder of the kidney's proximal tubules, which leads to a loss of essential substances such as glucose, amino acids, uric acid, phosphate, and bicarbonate in the urine. This condition can be either inherited or acquired and is associated with various underlying diseases and environmental factors.

Pathophysiology

The proximal tubules of the kidneys are responsible for reabsorbing approximately 65% of the glomerular filtrate, including essential nutrients and electrolytes. In Fanconi's syndrome, there is a generalized dysfunction of these tubules, leading to a failure in reabsorption. This results in excessive urinary excretion of substances that are normally reabsorbed, causing metabolic imbalances.

Genetic Causes

Inherited forms of Fanconi's syndrome can be associated with genetic disorders such as cystinosis, galactosemia, glycogen storage disease, and Wilson's disease. These conditions affect the function of the proximal tubules through various mechanisms, such as the accumulation of toxic substances or metabolic defects.

Acquired Causes

Acquired Fanconi's syndrome can result from exposure to certain drugs, heavy metals, or other toxins. Notable causes include:

• Tenofovir and other antiretroviral drugs
• Ifosfamide, a chemotherapy agent
• Heavy metals such as lead and cadmium
• Multiple myeloma

Clinical Features

Patients with Fanconi's syndrome may present with a variety of symptoms due to the loss of essential nutrients and electrolytes. Common clinical features include:

• Polyuria and polydipsia due to loss of water and electrolytes
• Growth retardation in children
• Bone pain and fractures due to phosphate wasting and resultant osteomalacia
• Metabolic acidosis due to bicarbonate loss
• Hypokalemia and hypophosphatemia

Diagnosis

The diagnosis of Fanconi's syndrome is based on laboratory findings of:

• Glycosuria with normal blood glucose levels
• Aminoaciduria
• Phosphaturia
• Bicarbonaturia
• Hypophosphatemia and metabolic acidosis

Further investigations may include genetic testing for inherited forms or tests for underlying conditions in acquired cases.

Management

Treatment of Fanconi's syndrome focuses on addressing the underlying cause and correcting metabolic imbalances. Management strategies include:

• Supplementation of phosphate, bicarbonate, and potassium
• Adequate hydration
• Treatment of the underlying disease or discontinuation of the offending drug

Prognosis

The prognosis of Fanconi's syndrome varies depending on the underlying cause. Inherited forms may require lifelong management, while acquired forms may improve with treatment of the underlying condition.

Also see

• Proximal renal tubular acidosis
• Cystinosis
• Wilson's disease
• Multiple myeloma