title: Disturbed lipid metabolism in glycogen storage disease type 1.
abstract: Glycogen storage disease type 1 (GSD1) is an inborn error of metabolism caused by deficiency of glucose-6-phosphatase, the enzyme catalysing the conversion of glucose-6-phosphate (G6P) to glucose. GSD1 is associated with severe hyperlipidaemia and hepatic steatosis. The underlying mechanisms responsible for these abnormalities in lipid metabolism are only partly known. This review summarises data available on hyperlipidaemia and steatosis in GSD1 and postulates new hypotheses for unresolved issues. Evidence indicates that lipid clearance from the blood compartment is decreased in GSD1. Furthermore, in two GSD1a patients synthesis of palmitate, an indicator of de novo lipogenesis, and cholesterol were found to be increased 40-fold and 7-fold, respectively. Elevated hepatic G6P levels may play a regulatory role in lipid synthesis via activation of transcription of lipogenic genes. In addition, accelerated glycolysis will supply acetyl-CoA molecules required for lipogenesis. It is as yet unclear whether hepatic secretion of lipids in the form of very low density lipoprotein-triglycerides (VLDL-TG) is altered in GSD1 patients: we recently found unaffected VLDL-TG secretion rates in an acute animal model of GSD1b. Hepatic steatosis, which is invariably present in GSD1 is probably mainly caused by an increased free fatty acid flux from adipose tissue to the liver and, to a limited extent, by increased de novo lipogenesis.
  
  
  CONCLUSIONS
  future studies, using novel stable isotope methodologies, are warranted to further clarify the disturbances in lipid and lipoprotein metabolism in glycogen storage disease type 1 and the role of glucose-6-phosphate herein.
authors.affiliation: Centre for Liver, Digestive and Metabolic Diseases, Room Y2117, CMCIV, University Hospital Groningen, Hanzeplein 1, PO Box 30001, 9700 RB Groningen The Netherlands. R.H.J.Bandsma@med.rug.nl
authors.forename: Robert H J
authors.initials: RH
authors.lastname: Bandsma
authors.forename: G Peter A
authors.initials: GP
authors.lastname: Smit
authors.forename: Folkert
authors.initials: F
authors.lastname: Kuipers
mesh_terms: D000818:Animals; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D005953:Glycogen Storage Disease Type I / Q000150:complications* / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D006949:Hyperlipidemias / Q000209:etiology / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008107:Liver Diseases / Q000209:etiology / Q000378:metabolism*; D014157:Transcription Factors / Q000502:physiology; D014280:Triglycerides / Q000378:metabolism
chemical_list: D014157:Transcription Factors; D014280:Triglycerides; D005952:Glucose-6-Phosphatase