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Fanconi syndrome consists of multiple defects in renal proximal tubular reabsorption, causing glucosuria, phosphaturia, generalized aminoaciduria, and HCO₃ wasting. Symptoms in children are failure to thrive, growth retardation, and rickets. Symptoms in adults are osteomalacia and muscle weakness. Diagnosis is by showing glucosuria, phosphaturia, and aminoaciduria. Treatment is HCO₃ replacement and measures directed at renal failure.

Etiology

Fanconi syndrome can be

• Hereditary
• Acquired

Hereditary Fanconi syndrome: This disorder usually accompanies another genetic disorder, particularly cystinosis. Cystinosis is an inherited (autosomal recessive) metabolic disorder in which cystine accumulates within cells and tissues (and is not excreted to excess in the urine as occurs in cystinuria—see Congenital Renal Transport Abnormalities: Cystinuria); besides renal tubular dysfunction, other complications of cystinosis include eye disorders, hepatomegaly, hypothyroidism, and other manifestations.

Fanconi syndrome may also accompany Wilson's disease, hereditary fructose intolerance, galactosemia, glycogen storage disease, oculocerebrorenal syndrome (Lowe syndrome), mitochondrial cytopathies, and tyrosinemia. Inheritance patterns vary with the associated disorder.

Acquired Fanconi syndrome: This disorder may be caused by various drugs, including certain cancer chemotherapy drugs (eg, ifosfamide Some Trade Names
IFEX
MITOXANA
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, streptozocin Some Trade Names
ZANOSAR
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), antiretrovirals (eg, didanosine Some Trade Names
VIDEX
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, cidofovir Some Trade Names
VISTIDE
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), and outdated tetracycline Some Trade Names
ACHROMYCIN V
TETRACYN
TETREX
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. All of these drugs are nephrotoxic. Acquired Fanconi syndrome also may occur after renal transplantation and in patients with multiple myeloma, amyloidosis, intoxication with heavy metals or other chemicals, or vitamin D deficiency.

Pathophysiology

Various defects of proximal tubular transport function occur, including impaired resorption of glucose, phosphate, amino acids, HCO₃, uric acid, water, K, and Na. The aminoaciduria is generalized, and, unlike that in cystinuria, increased cystine excretion is a minor component. The basic pathophysiologic abnormality is unknown but may involve a mitochondrial disturbance. Low values of serum phosphate cause rickets, which is worsened by decreased proximal tubular conversion of vitamin D to its active form.

Symptoms and Signs

In hereditary Fanconi syndrome, the chief clinical features—proximal tubular acidosis, hypophosphatemic rickets, hypokalemia, polyuria, and polydipsia—usually appear in infancy.

When Fanconi syndrome occurs because of cystinosis, failure to thrive and growth retardation are common. The retinas show patchy depigmentation. Interstitial nephritis develops, leading to progressive renal failure that may be fatal before adolescence.

In acquired Fanconi syndrome, adults present with the laboratory abnormalities of renal tubular acidosis (proximal type 2), hypophosphatemia, and hypokalemia. They may present with symptoms of bone disease (osteomalacia) and muscle weakness.

Diagnosis

• Urine testing for glucose, phosphates, and amino acids

Diagnosis is made by showing the abnormalities of renal function, particularly glucosuria (in the presence of normal serum glucose), phosphaturia, and aminoaciduria. In cystinosis, slit-lamp examination may show cystine crystals in the cornea.

Treatment

• Sometimes NaHCO₃ or KHCO₃ or Na citrate or K citrate
• Sometimes K supplementation

Other than removing the offending nephrotoxin, there is no specific treatment. Acidosis may be lessened by giving tablets or solutions of Na or K HCO₃ or citrate, eg, Shohl's solution (Na citrate and citric acid; 1 mL is equivalent to 1 mmol of HCO₃) given 1 mEq/kg bid to tid or 5 to 15 mL after meals and at bedtime. K depletion may require replacement therapy with a K-containing salt. Hypophosphatemic rickets can be treated as described (see Congenital Renal Transport Abnormalities: Hypophosphatemic Rickets). Renal transplantation has been successful in treating renal failure. However, when cystinosis is the underlying disease, progressive damage may continue in other organs and eventually result in death.

Last full review/revision September 2009 by Peter C. Brazy, MD

Content last modified September 2009