Fanconi syndrome

Overview

Fanconi syndrome is a rare disorder of kidney function that affects the proximal renal tubules, resulting in impaired reabsorption of various substances that are normally reabsorbed into the bloodstream. These include glucose, amino acids, phosphate, bicarbonate, and other electrolytes. The syndrome is characterized by excessive urinary loss of these substances, leading to metabolic imbalances and complications such as rickets, growth failure, and acidosis. Fanconi syndrome can occur as a primary (inherited) condition or secondary to other diseases or toxins.

Causes

Fanconi syndrome can be categorized into inherited (primary) and acquired (secondary) forms. Causes include:

• Inherited causes:

  • Cystinosis: The most common inherited cause in children, where cystine accumulates in kidney cells.

  • Wilson's disease: A disorder of copper metabolism.

  • Galactosemia or hereditary fructose intolerance: Metabolic disorders affecting sugar processing.

  • Lowe syndrome and Dent disease: X-linked disorders affecting kidney tubule function.

• Acquired causes:

  • Exposure to certain drugs: e.g., ifosfamide, tenofovir, outdated tetracyclines.

  • Heavy metals: e.g., lead, cadmium, or mercury toxicity.

  • Multiple myeloma and other systemic conditions that damage the kidneys.

  • Vitamin D deficiency or use of certain chemotherapy agents.

Symptoms

The symptoms of Fanconi syndrome vary depending on the severity and underlying cause but commonly include:

• Polyuria: Excessive urination.

• Polydipsia: Excessive thirst due to fluid loss.

• Rickets or osteomalacia: Bone softening due to phosphate wasting.

• Growth retardation: Especially in children with the inherited form.

• Muscle weakness: Due to electrolyte imbalances, particularly low potassium levels.

• Metabolic acidosis: From loss of bicarbonate in the urine.

• Glycosuria: Presence of glucose in the urine despite normal blood sugar levels.

Diagnosis

Diagnosis of Fanconi syndrome involves identifying the loss of multiple substances in the urine and associated metabolic disturbances. Diagnostic steps include:

• Urinalysis: Shows glucose, amino acids, phosphate, and bicarbonate in the urine.

• Blood tests: Reveal low levels of phosphate, bicarbonate, potassium, and possible metabolic acidosis.

• Arterial blood gas (ABG): To confirm metabolic acidosis.

• Renal function tests: To assess kidney health.

• Genetic testing: In suspected inherited cases to identify underlying mutations.

• Imaging studies: Bone X-rays may show signs of rickets or osteomalacia.

Treatment

Treatment of Fanconi syndrome focuses on correcting metabolic imbalances, managing symptoms, and addressing the underlying cause. Approaches include:

• Electrolyte replacement: Oral phosphate, potassium, and bicarbonate supplements to restore balance.

• Vitamin D and calcium supplementation: To treat or prevent rickets and support bone health.

• High fluid intake: To compensate for urinary losses and prevent dehydration.

• Discontinuation of offending drugs: In acquired cases related to medications or toxins.

• Treatment of underlying disease: For example, cysteamine in cystinosis, chelation therapy in Wilson's disease, or managing multiple myeloma.

• Monitoring growth and development: Regular follow-ups for children to ensure normal growth and skeletal health.

Prognosis

The prognosis for individuals with Fanconi syndrome depends on the underlying cause and the effectiveness of treatment. In acquired cases, symptoms may resolve if the offending agent is removed early. In inherited forms, especially those diagnosed in childhood, ongoing treatment and monitoring are necessary to manage symptoms and prevent complications. With appropriate care, many patients can lead relatively normal lives, although chronic kidney disease may develop in some cases over time.