What is the pathogenesis of Fanconi syndrome?

Updated: Feb 09, 2018
  • Author: Sahar Fathallah-Shaykh, MD; Chief Editor: Craig B Langman, MD  more...
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Answer

The pathogenesis of the disease is unclear. Experimental evidence points to cellular disturbances in carbohydrate metabolism and in the galactosylation of proteins. Accumulation of galactose-1-phosphate may deplete the cells of phosphate and compromise energy metabolism. Generation of galactitol from galactose may contribute to the development of cataracts.

Elimination of galactose from the diet results in reversal of symptoms, including the cataracts. Yet, children with this disease fail to thrive, have developmental delays, and exhibit ovarian dysfunction.

Hereditary fructose intolerance is caused by a deficiency in fructose-1-phosphate aldolase activity. This enzyme cleaves fructose-1-phosphate into D-glyceraldehyde and dihydroxyacetone phosphate, which, in turn, is converted into glucose or carbon dioxide and water.

Incidence is approximately 1 case per 20,000 live births. The disease becomes apparent when foods that contain fructose, sucrose, or sorbitol are introduced in the diet. Ingestion of such foods causes vomiting, severe dehydration, hemorrhagic diathesis, and acute liver and kidney failure. A full Fanconi syndrome is also present and can persist long after fructose has been excluded from the diet.

Continuous exposure to fructose results in hepatic insufficiency, nephrocalcinosis, and failure to thrive. Animal and human evaluations reveal that fructose loading leads to intracellular phosphate depletion and decreased ATP. This effect occurs in individuals with or without enzyme deficiencies but is more severe in the former group. Treatment of hereditary fructose intolerance consists of strict avoidance of fructose-containing foods.


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