Cited by 81Glycogen Storage Diseases and MyoclonusMetabolism and Genetic DisordersLipid metabolism and disorders

Disturbed lipid metabolism in glycogen storage disease type 1

Bandsma, Robert, Smit, Peter, Kuipers, Folkert·2002·European Journal of Pediatrics

Abstract

Unlabelled 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.Conclusion 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.

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Crossref · 10.1007/s00431-002-1007-8

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Authors
Bandsma, R., Smit, P., & Kuipers, F.
Affiliations
University Medical Center Groningen (NL)
Corresponding author
Bandsma, Robert
Venue
European Journal of Pediatrics
Published
2002-01-01
Volume
161
Issue
0
Pages
S65-S69
ISSN
  • 0340-6199 (ISSN-L)
  • 1432-1076
OpenAlex
W2084887776
Cited by
81
References
46
Citations by year
2026: 3 · 2025: 2 · 2024: 3 · 2023: 8 · 2022: 3 · 2021: 4 · 2020: 7 · 2019: 5 · 2018: 5 · 2017: 3 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 4 · 2012: 1
FWCI
1.00
Type
journal article
Language
en
Open access
closed
Locations
  • European Journal of Pediatrics (publishedVersion)
  • PubMed (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
Topics
  • Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords
glycogen storage disease type 1, glucose-6-phosphatase deficiency, hyperlipidemia, hepatic steatosis, lipid metabolism, de novo lipogenesis, cholesterol biosynthesis, glucose-6-phosphate, VLDL triglyceride secretion, lipoprotein metabolism
MeSH terms
Animals, Glucose-6-Phosphatase, Glycogen Storage Disease Type I, Glycolysis, Humans, Hyperlipidemias, Liver, Liver Diseases, Transcription Factors, Triglycerides

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