Fanconi syndrome is a disorder characterized by hereditary or acquired dysfunction of multiple transport processes in the proximal renal tubules. It involves defects in the reabsorption of various substances, including amino acids, glucose, sodium, potassium, calcium, phosphate, bicarbonate, uric acid, and proteins.
Etiology
Fanconi syndrome can be classified as primary or secondary.
Primary Fanconi syndrome is often inherited in an autosomal recessive manner and may occur alone or in association with other congenital genetic disorders.
Secondary Fanconi syndrome can result from conditions such as chronic interstitial nephritis, medullary cystic kidney disease, paraproteinemia, multiple myeloma, or toxic renal damage caused by heavy metals or other toxins.
Clinical Manifestations
The clinical presentation of Fanconi syndrome is highly variable and depends on the underlying cause and severity of the condition.
In children, it is often associated with congenital diseases such as cystinosis, tyrosinemia, Wilson's disease, or other metabolic disorders. In addition to symptoms of the primary disease, children may present with polyuria, polydipsia, dehydration, rickets, and growth retardation.
In adults, it is more commonly caused by acquired conditions, such as drug or toxin exposure, paraproteinemia, or multiple myeloma. The presentation is often insidious, but urine and blood tests reveal a range of abnormalities.
Due to the excessive loss of substances reabsorbed by the proximal tubules in urine, Fanconi syndrome manifests as non-selective renal aminoaciduria. Hyperphosphaturia is the primary cause of rickets and osteomalacia. Bicarbonate loss in urine can lead to type II renal tubular acidosis.
Other findings may include increased urinary excretion of glucose, potassium, sodium, and uric acid. Mild proteinuria, characterized by low-molecular-weight proteins, may also occur. In advanced stages, renal failure may develop.
The substantial loss of solutes and electrolytes in the urine can result in metabolic acidosis, hypokalemia, hyponatremia, hypouricemia, hypophosphatemia, and associated symptoms.
Laboratory Tests
Laboratory investigations include:
- Urinalysis, including tests for glucose and amino acids in the urine.
- Blood and urinary electrolyte measurements.
- Imaging studies and etiological assessments.
Diagnosis
The diagnosis is based on the presence of characteristic clinical features. Renal glycosuria, non-selective aminoaciduria, and hyperphosphaturia are essential diagnostic criteria.
Treatment
Treatment involves addressing the underlying disease. If caused by drugs or toxins, discontinuation of the offending agent is necessary. Symptomatic management is also important. Proximal renal tubular acidosis should be managed according to relevant guidelines. Severe hypophosphatemia may require supplementation with neutral phosphate and calcitriol. Hypouricemia, aminoaciduria, and glycosuria generally do not require specific treatment.