Fanconi syndrome

Not to be confused with Fanconi anemia.
Fanconi syndrome
Classification and external resources
Specialty endocrinology
ICD-10 E72.0
ICD-9-CM 270.0
DiseasesDB 11687
MedlinePlus 000333
eMedicine ped/756
MeSH D005198

Fanconi syndrome or Fanconi's syndrome (English /fɑːnˈkoʊni/, /fæn-/) is a syndrome of inadequate reabsorption in the proximal renal tubules[1] of the kidney. The syndrome can be caused by various underlying congenital or acquired diseases, by toxicity (for example, from toxic heavy metals), or by adverse drug reactions.[2] It results in various small molecules of metabolism being passed into the urine instead of being reabsorbed from the tubular fluid (for example, glucose, amino acids, uric acid, phosphate, and bicarbonate). Fanconi syndrome affects the proximal tubules, namely, the proximal convoluted tubule (PCT), which is the first part of the tubule to process fluid after it is filtered through the glomerulus, and the proximal straight tubule (pars recta), which leads to the descending limb of the loop of Henle.

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 diseases rickets and osteomalacia (even with adequate vitamin D and calcium levels), because phosphate is necessary for bone development in children and even for ongoing bone metabolism in adults.[3]

Eponym

It is named after Guido Fanconi, a Swiss pediatrician, although various other scientists, including George Lignac, contributed to its study. It should not be confused with Fanconi anemia, a separate disease.

Clinical features

The clinical features of proximal renal tubular acidosis are:

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

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.[4]

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),[5] galactosemia, glycogen storage diseases, and hereditary fructose intolerance.

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

A recently described form of this disease is due to a mutation in the peroxisomal protein EHHADH.[7] 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.[8][9] In the HIV population, Fanconi syndrome can develop secondary to the use of an antiretroviral regimen containing tenofovir and didanosine.[10] Lead poisoning also leads to Fanconi syndrome.[11]

Multiple myeloma or monoclonal gammopathy of undetermined significance can also cause the condition.[12]

Treatment

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

See also

References

  1. ↑ "Fanconi syndrome" at Dorland's Medical Dictionary
  2. ↑ Fanconi Syndrome at Merck Manual Home Health Handbook
  3. ↑ Magen D, Berger L, Coady MJ, et al. (March 2010). "A loss-of-function mutation in NaPi-IIa and renal Fanconi's syndrome". N. Engl. J. Med. 362 (12): 1102–9. doi:10.1056/NEJMoa0905647. PMID 20335586.
  4. ↑ Fanconi Syndrome at eMedicine
  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. PMC 2810370Freely accessible. PMID 19156444.
  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.
  7. ↑ Assmann N, Dettmer K, Simbuerger JM, Broeker C, Nuernberger N, Renner K, Courtneidge H4, Klootwijk ED, Duerkop A, Hall A, Kleta R, Oefner PJ, Reichold M, Reinders J (2016) Renal Fanconi syndrome is caused by a mistargeting-based mitochondriopathy. Cell Rep pii: S2211-1247 (16) 30464-30468 doi: 10.1016/j.celrep.2016.04.037
  8. ↑ Viread Label Information, U.S. Food and Drug Administration (FDA)), 2008-04-11
  9. ↑ Tenofovir (Viread) Associated with Mild Kidney Function Impairment, but not Clinically Relevant Renal Disease, hivandhepatitis.com, 2008-10-14
  10. ↑ Irizarry-Alvarado JM, Dwyer JP, Brumble LM, Alvarez S, Mendez JC (March 2009). "Proximal tubular dysfunction associated with tenofovir and didanosine causing Fanconi syndrome and diabetes insipidus: a report of 3 cases". AIDS Read. 19 (3): 114–21. PMID 19334328.
  11. ↑ 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): 105–p110. doi:10.1159/000083981. PMID 15722646.
  12. ↑ 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.
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