Fanconi syndrome

Not to be confused with Fanconi anemia.

Fanconi syndrome
Classification and external resources
Specialty
ICD-10	E72.0
ICD-9-CM	270.0
DiseasesDB	11687
MedlinePlus	000333
eMedicine	ped/756
Patient UK	Fanconi syndrome
MeSH	D005198

Fanconi syndrome (also known as Fanconi's syndrome) is a disease of the proximal renal tubules of the kidney in which glucose, amino acids, uric acid, phosphate and bicarbonate are passed into the urine, instead of being reabsorbed. Fanconi syndrome affects the proximal tubule, which is the first part of the tubule to process fluid after it is filtered through the glomerulus. It may be inherited, or caused by drugs or heavy metals.

Different forms of Fanconi syndrome can affect different functions of the proximal tubule, and result in different complications. The loss of bicarbonate results in type 2 or proximal renal tubular acidosis. The loss of phosphate results in the bone disease rickets (even with adequate vitamin D and calcium), because phosphate is necessary for bone development.

Eponym

It is named after Guido Fanconi, a Swiss pediatrician; this may be a misnomer, since Fanconi himself never identified it as a syndrome; though, as in the case of Goodpasture's syndrome, it is customary to name a syndrome after the first person to note a constellation of symptoms as occurring together.

It should not be confused with Fanconi anemia, a separate disease.

Clinical features

Main article: renal tubular acidosis

The clinical features of proximal renal tubular acidosis are:

• Polyuria, polydipsia and dehydration
• Hypophosphatemic rickets (in children) and osteomalacia (in adults)
• Growth failure
• Acidosis
• Hypokalemia
• Hyperchloremia

Other features of the generalized proximal tubular dysfunction of the Fanconi syndrome are:

• Hypophosphatemia/hyperphosphaturia
• Glycosuria
• Proteinuria/aminoaciduria
• Hyperuricosuria

Causes

In contrast to Hartnup disease and related tubular conditions, Fanconi syndrome affects the transport of many different substances, so is not considered to be a defect in a specific channel, but a more general defect in the function of the proximal tubules.

Different diseases underlie Fanconi syndrome; they can be inherited, congenital, or acquired.

Inherited

Cystinosis is the most common cause of Fanconi syndrome in children.

Other recognised causes are Wilson's disease (a genetically inherited condition of copper metabolism), Lowe syndrome, tyrosinemia (type I), galactosemia, glycogen storage diseases, and hereditary fructose intolerance.

Two forms, Dent's disease and Lowe syndrome, are X linked.

A recently described form of this disease is due to a mutation in the peroxisomal protein EHHADH. This mutation misdirects the EHHADH to the mitochondria. This interfers with respiratory complex I and with beta oxidation of fatty acids. The end result is a decrease in the ability of the mitochondria to produce ATP.

Acquired

It is possible to acquire this disease later in life.

Causes include ingesting expired tetracyclines (where tetracycline changes to form epitetracycline and anhydrotetracycline which damage proximal tubule), and as a side effect of tenofovir in cases of pre-existing renal impairment. In the HIV population, Fanconi syndrome can develop secondary to the use of an antiretroviral regimen containing tenofovir and didanosine. Lead poisoning also leads to Fanconi syndrome.

Multiple myeloma or monoclonal gammopathy of undetermined significance can also cause the condition.

Treatment

Treatment of children with Fanconi syndrome mainly consists of replacement of substances lost in the urine (mainly fluid and bicarbonate).

See also

• Familial renal disease in animals for Fanconi syndrome in Basenjis