Fanconi syndrome

Not to be confused with Fanconi anemia.

Fanconi syndrome
Classification and external resources
ICD-10	E72.0
ICD-9	270.0
DiseasesDB	11687
eMedicine	ped/756
MeSH	D005198

Falconi syndrome (also known as Fanconi's syndrome) is a disease of the proximal renal tubules^[1] 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.^[2]

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.^{[citation needed]} The loss of phosphate results in the bone disease rickets (even with adequate vitamin D and calcium), because phosphate is necessary for bone development.^[3]

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/phosphaturia
• Glycosuria
• Proteinuria/aminoaciduria
• Hyperuricosuria

Causes

In contrast to Hartnup disease and related tubular conditions, Fanconi syndrome affects the transport of many different substances, and therefore is not considered to be a defect in a specific channel, but a more general defect in the function of the proximal tubules.^[4]

There are different diseases underlying Fanconi syndrome. They can be inherited, congenital or acquired.

Inherited

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

Other recognised causes of Fanconi's syndrome are Wilson's disease (a genetically inherited condition of copper metabolism), Lowe syndrome, tyrosinemia (Type I),^[5] galactosemia, glycogen storage diseases, and fructose intolerance.

Two forms, Dent's disease and Lowe syndrome, are X linked.^[6]

Acquired

It is possible to acquire this disease later in life.

Causes include ingesting expired tetracyclines, and as a side effect of tenofovir in cases of preexisting renal impairment.^[7][8] In the HIV population, Fanconi syndrome can develop secondary to use of an antiretroviral regimen containing tenofovir and didanosine.^[9] Lead poisoning also leads to Fanconi syndrome.^[10]

Monoclonal gammopathy of undetermined significance can also cause the condition.^[11]

Multiple myeloma is also a known cause.

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

References

1. ^ "Fanconi syndrome" at Dorland's Medical Dictionary
2. ^ Fanconi Syndrome at Merck Manual Home Health Handbook
3. ^ A loss-of-function mutation in NaPi-IIa and renal Fanconi's syndrome, N Engl J Med 362:1102
4. ^ "Fanconi Syndrome: eMedicine Pediatrics: General Medicine". http://emedicine.medscape.com/article/981774-overview. 
5. ^ Cochat P, Pichault V, Bacchetta J et al. (March 2010). "Nephrolithiasis related to inborn metabolic diseases". Pediatr. Nephrol. 25 (3): 415–424. doi:10.1007/s00467-008-1085-6. ISBN 0046700810856. PMC 2810370. PMID 19156444. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2810370. 
6. ^ Vilasi A, Cutillas PR, Maher AD et al. (August 2007). "Combined proteomic and metabonomic studies in three genetic forms of the renal Fanconi syndrome". Am. J. Physiol. Renal Physiol. 293 (2): F456–F467. doi:10.1152/ajprenal.00095.2007. PMID 17494094. http://ajprenal.physiology.org/cgi/pmidlookup?view=long&pmid=17494094. 
7. ^ Viread Label Information, U.S. Food and Drug Administration (FDA)), 2008-04-11
8. ^ Tenofovir (Viread) Associated with Mild Kidney Function Impairment, but not Clinically Relevant Renal Disease, hivandhepatitis.com, 2008-10-14
9. ^ Irizarry-Alvarado JM, Dwyer JP, Brumble LM, et al. Proximal tubular dysfunction associated with tenofovir and didanosine causing Fanconi syndrome and diabetes insipidus: a report of 3 cases. AIDS Reader. 2009;19:114-121.
10. ^ Barbier O, Jacquillet G, Tauc M, Cougnon M, Poujeol P (2005). "Effect of heavy metals on, and handling by, the kidney". Nephron Physiol 99 (4): p105–p110. doi:10.1159/000083981. PMID 15722646. http://content.karger.com/produktedb/produkte.asp?typ=pdf&file=NEP2005099004105. 
11. ^ Hashimoto T, Arakawa K, Ohta Y et al. (2007). "Acquired fanconi syndrome with osteomalacia secondary to monoclonal gammopathy of undetermined significance" (– ^{Scholar search}). Intern. Med. 46 (5): 241–245. doi:10.2169/internalmedicine.46.1882. PMID 17329920. http://joi.jlc.jst.go.jp/JST.JSTAGE/internalmedicine/46.1882?from=PubMed. ^{[dead link]}