Medicine:Fanconi syndrome

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Fanconi syndrome
Other namesFanconi's syndrome

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 loop of Henle.[citation needed]

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]

Presentation

Main page: Medicine:Renal tubular acidosis

The clinical features of proximal renal tubular acidosis are:[citation needed]

Other features of the generalized proximal tubular dysfunction of the Fanconi syndrome are:[citation needed]

  • 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.[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.[citation needed]

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 interferes with respiratory complex I and with beta oxidation of fatty acids. The result is a decrease in the ability of the mitochondria to produce ATP.[citation needed]

It was shown that a specific mutation (R76W) of HNF4A, a gene encoding a transcription factor, causes Fanconi syndrome in human.[8] In the kidney, HNF4A is expressed in the proximal tubules specifically.[9] Deletion of Hnf4a in the developing mouse kidney caused Fanconi syndrome phenotypes including polyruia, polydipsia, glycosuria, and phosphaturia.[10] The Hnf4a mutant kidney showed a defect in the formation of proximal tubules.[10]

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 the proximal tubule), and as a side effect of tenofovir in cases of pre-existing renal impairment.[11][12] In the HIV population, Fanconi syndrome can develop secondary to the use of an antiretroviral regimen containing tenofovir and didanosine.[13] Lead poisoning also leads to Fanconi syndrome.[14]

Multiple myeloma or monoclonal gammopathy of undetermined significance can also cause the condition.[15]

Additionally, Fanconi syndrome can develop as a secondary or tertiary effect of certain autoimmune disorders.[16][17]

Diagnosis

Urine routine, might not be completely reliable but is an important indicator.[citation needed]

Treatment

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

Eponym

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

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". The New England Journal of Medicine 362 (12): 1102–9. March 2010. doi:10.1056/NEJMoa0905647. PMID 20335586. 
  4. ↑ Fanconi Syndrome at eMedicine
  5. ↑ "Nephrolithiasis related to inborn metabolic diseases". Pediatric Nephrology 25 (3): 415–24. March 2010. doi:10.1007/s00467-008-1085-6. PMID 19156444. 
  6. ↑ "Combined proteomic and metabonomic studies in three genetic forms of the renal Fanconi syndrome". American Journal of Physiology. Renal Physiology 293 (2): F456-67. August 2007. doi:10.1152/ajprenal.00095.2007. PMID 17494094. 
  7. ↑ "Renal Fanconi Syndrome Is Caused by a Mistargeting-Based Mitochondriopathy". Cell Reports 15 (7): 1423–1429. May 2016. doi:10.1016/j.celrep.2016.04.037. PMID 27160910. http://discovery.ucl.ac.uk/1493687/1/Assmann_Renal%20Fanconi%20Syndrome%20Is%20Caused%20by%20a%20Mistargeting-Based%20Mitochondriopathy%20VoR.pdf. 
  8. ↑ "The HNF4A R76W mutation causes atypical dominant Fanconi syndrome in addition to a β cell phenotype". Journal of Medical Genetics 51 (3): 165–9. March 2014. doi:10.1136/jmedgenet-2013-102066. PMID 24285859. 
  9. ↑ "Deep Sequencing in Microdissected Renal Tubules Identifies Nephron Segment-Specific Transcriptomes". Journal of the American Society of Nephrology 26 (11): 2669–77. November 2015. doi:10.1681/ASN.2014111067. PMID 25817355. PMC 4625681. https://jasn.asnjournals.org/content/26/11/2669. 
  10. ↑ 10.0 10.1 "Hnf4a deletion in the mouse kidney phenocopies Fanconi renotubular syndrome". JCI Insight 3 (14). July 2018. doi:10.1172/jci.insight.97497. PMID 30046000. 
  11. ↑ Viread Label Information, U.S. Food and Drug Administration (FDA), 2008-04-11
  12. ↑ Tenofovir (Viread) Associated with Mild Kidney Function Impairment, but not Clinically Relevant Renal Disease, hivandhepatitis.com, 2008-10-14
  13. ↑ "Proximal tubular dysfunction associated with tenofovir and didanosine causing Fanconi syndrome and diabetes insipidus: a report of 3 cases". The AIDS Reader 19 (3): 114–21. March 2009. PMID 19334328. 
  14. ↑ "Effect of heavy metals on, and handling by, the kidney". Nephron Physiology 99 (4): 105–10. 2005. doi:10.1159/000083981. PMID 15722646. 
  15. ↑ "Acquired fanconi syndrome with osteomalacia secondary to monoclonal gammopathy of undetermined significance". Internal Medicine 46 (5): 241–5. 2007. doi:10.2169/internalmedicine.46.1882. PMID 17329920. 
  16. ↑ "Fanconi Syndrome". http://the-medical-dictionary.com/fanconi_syndrome_article_5.htm. 
  17. ↑ "Fanconi's syndrome and distal (type 1) renal tubular acidosis in a patient with primary Sjögren's syndrome with monoclonal gammopathy of undetermined significance". Clinical Nephrology 65 (6): 427–32. June 2006. doi:10.5414/CNP65427. PMID 16792139. 

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