Etiology of Fanconi Syndrome
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 Cystinuria Cystinuria is an inherited defect of the renal tubules in which reabsorption of cystine (the homodimer of the amino acid cysteine) is impaired, urinary excretion is increased, and cystine stones... read more ). Besides renal tubular dysfunction, other complications of cystinosis include eye disorders, hepatomegaly, hypothyroidism, and other manifestations.
Fanconi syndrome may also accompany Wilson disease Wilson Disease Wilson disease results in accumulation of copper in the liver and other organs. Hepatic or neurologic symptoms develop. Diagnosis is based on a low serum ceruloplasmin level, high urinary excretion... read more 
, hereditary fructose intolerance Fructose Metabolism Disorders Deficiency of enzymes that metabolize fructose may be asymptomatic or cause hypoglycemia. Fructose is a monosaccharide that is present in high concentrations in fruit and honey and is a constituent... read more , galactosemia Galactosemia Galactosemia is a carbohydrate metabolism disorder caused by inherited deficiencies in enzymes that convert galactose to glucose. Symptoms and signs include hepatic and renal dysfunction, cognitive... read more , oculocerebrorenal syndrome (Lowe syndrome), mitochondrial cytopathies, and tyrosinemia Tyrosine Metabolism Disorders Tyrosine is an amino acid that is a precursor of several neurotransmitters (eg, <span class="disableDrug">dopamine</span>, <span class="disableDrug">norepinephrine<... read more . 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certain cancer chemotherapy drugs (eg, ifosfamide, streptozocin), antiretrovirals (eg, didanosine, cidofovir), and outdated tetracycline. All of these drugs are nephrotoxic. Acquired Fanconi syndrome also may occur after renal transplantation and in patients with multiple myeloma Multiple Myeloma Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones causing... read more 
, amyloidosis Amyloidosis Amyloidosis is any of a group of disparate conditions characterized by extracellular deposition of insoluble fibrils composed of misaggregated proteins. These proteins may accumulate locally... read more 
, intoxication with heavy metals or other chemicals, or vitamin D deficiency Vitamin D Deficiency and Dependency Inadequate exposure to sunlight predisposes to vitamin D deficiency. Deficiency impairs bone mineralization, causing rickets in children and osteomalacia in adults and possibly contributing... read more .
Pathophysiology of Fanconi Syndrome
Various defects of proximal tubular transport function occur, including impaired resorption of glucose, phosphate, amino acids, bicarbonate, uric acid, water, potassium, and sodium. 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 levels of serum phosphate cause rickets, which is worsened by decreased proximal tubular conversion of vitamin D to its active form.
Symptoms and Signs of Fanconi Syndrome
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 Tubulointerstitial Nephritis Tubulointerstitial nephritis is primary injury to renal tubules and interstitium resulting in decreased renal function. The acute form is most often due to allergic drug reactions or to infections... read more 
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—see Table: Some Features of Different Types of Renal Tubular Acidosis* Some Features of Different Types of Renal Tubular Acidosis* 
), hypophosphatemia, and hypokalemia. They may present with symptoms of bone disease (osteomalacia) and muscle weakness.
Diagnosis of Fanconi Syndrome
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 of Fanconi Syndrome
Sometimes sodium bicarbonate or potassium bicarbonate or sodium citrate or potassium citrate
Sometimes potassium supplementation
Other than removing the offending nephrotoxin, there is no specific treatment.
Acidosis may be lessened by giving tablets or solutions of sodium bicarbonate or potassium bicarbonate or sodium citrate or potassium citrate, eg, Shohl’s solution (sodium citrate and citric acid; 1 mL is equivalent to 1 mEq or 1 mmol of bicarbonate) given 1 mEq/kg (1 mmol/L) bid to tid or 5 to 15 mL after meals and at bedtime.
Potassium depletion may require replacement therapy with a potassium-containing salt.
Hypophosphatemic rickets Hypophosphatemic Rickets Hypophosphatemic rickets is a disorder characterized by hypophosphatemia, defective intestinal absorption of calcium, and rickets or osteomalacia unresponsive to vitamin D. It is usually hereditary... read more can be treated.
Kidney transplantation Kidney Transplantation Kidney transplantation is the most common type of solid organ transplantation. (See also Overview of Transplantation.) The primary indication for kidney transplantation is End-stage renal failure... read more 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.
Key Points
Multiple defects impair proximal tubular reabsorption of glucose, phosphate, amino acids, bicarbonate, uric acid, water, potassium, and sodium.
Fanconi syndrome is usually caused by a drug or accompanies another genetic disorder.
In hereditary Fanconi syndrome, proximal tubular acidosis, hypophosphatemic rickets, hypokalemia, polyuria, and polydipsia usually appear in infancy.
Test urine for glucosuria (particularly in the presence of normal serum glucose), phosphaturia, and aminoaciduria.
Treat by giving combinations as needed of potassium or sodium with either bicarbonate or citrate, or sometimes with just a supplemental potassium salt.
