Recent advances in the pathogenesis of hereditary fructose intolerance: implications for its treatment and the understanding of fructose-induced non-alcoholic fatty liver disease

Amee M. Buziau, Casper G. Schalkwijk, Coen D. A. Stehouwer, Dean R. Tolan*, Martijn C. G. J. Brouwers*

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

23 Citations (Web of Science)

Abstract

Hereditary fructose intolerance (HFI) is a rare inborn disease characterized by a deficiency in aldolase B, which catalyzes the cleavage of fructose 1,6-bisphosphate and fructose 1-phosphate (Fru 1P) to triose molecules. In patients with HFI, ingestion of fructose results in accumulation of Fru 1P and depletion of ATP, which are believed to cause symptoms, such as nausea, vomiting, hypoglycemia, and liver and kidney failure. These sequelae can be prevented by a fructose-restricted diet. Recent studies in aldolase B-deficient mice and HFI patients have provided more insight into the pathogenesis of HFI, in particular the liver phenotype. Both aldolase B-deficient mice (fed a very low fructose diet) and HFI patients (treated with a fructose-restricted diet) displayed greater intrahepatic fat content when compared to controls. The liver phenotype in aldolase B-deficient mice was prevented by reduction in intrahepatic Fru 1P concentrations by crossing these mice with mice deficient for ketohexokinase, the enzyme that catalyzes the synthesis of Fru 1P. These new findings not only provide a potential novel treatment for HFI, but lend insight into the pathogenesis of fructose-induced non-alcoholic fatty liver disease (NAFLD), which has raised to epidemic proportions in Western society. This narrative review summarizes the most recent advances in the pathogenesis of HFI and discusses the implications for the understanding and treatment of fructose-induced NAFLD.

Original languageEnglish
Pages (from-to)1709-1719
Number of pages11
JournalCellular and Molecular Life Sciences
Volume77
Issue number9
Early online date12 Nov 2019
DOIs
Publication statusPublished - May 2020

Keywords

  • Hereditary fructose intolerance
  • Glucokinase regulatory protein
  • Ketohexokinase
  • Fructose
  • De novo lipogenesis
  • Non-alcoholic fatty liver disease
  • HUMAN ALDOLASE-B
  • REGULATORY PROTEIN
  • URIC-ACID
  • PLASMA TRIGLYCERIDE
  • HEPATIC LIPOGENESIS
  • MOLECULAR ANALYSIS
  • METABOLIC SYNDROME
  • FASTING GLUCOSE
  • GLUCOKINASE
  • VARIANT

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