Normoglycemic Ketonemia as Biochemical Presentation in Ketotic Glycogen Storage Disease

  • Irene J. Hoogeveen
  • Rixt M. van der Ende
  • Francjan J. van Spronsen
  • Foekje de Boer
  • M. Rebecca Heiner-Fokkema
  • Terry G. J. DerksEmail author
Research Report
Part of the JIMD Reports book series (JIMD, volume 28)


Background: According to the textbooks, the ketotic glycogen storage disease (GSD) types 0, III, VI, IX, and XI are associated with fasting ketotic hypoglycemia and considered milder as gluconeogenesis is intact.

Methods: A retrospective cohort study of biochemical profiles from supervised clinical fasting studies is performed in ketotic GSD patients in our metabolic center. For data analysis, hypoglycemia was defined as plasma glucose concentration <2.6 mmol/L. Total KB was defined as the sum of blood acetoacetate and β-hydroxybutyrate concentrations. If the product of glucose and KB concentrations was greater than 10, a ketolysis defect was suspected.

Results: Data could be collected from 13 fasting studies in 12 patients with GSD III (n = 4), GSD VI (n = 3), and GSD IX (n = 5). Six patients remained normoglycemic with median glucose concentration of 3.9 mmol/L (range, 2.8–4.6 mmol/L) and median total KB concentration of 1.9 mmol/L (range, 0.6–5.1 mmol/L). The normoglycemic patients included type VI (3 out of 3) and type IX (3 out of 5) patients. All type III patients developed ketotic hypoglycemia. Interestingly, in five patients (one GSD III, one GSD VI, and three GSD IX), the biochemical profile suggested a ketolysis defect.

Conclusion: Normoglycemic ketonemia is a common biochemical presentation in patients with GSD types VI and IX, and ketonemia can precede hypoglycemia in all studied GSD types. Therefore, GSD VI and GSD IX should be added to the differential diagnosis of ketotic normoglycemia, and KB concentrations should be routinely measured in ketotic GSD patients.


Plasma Glucose Concentration Glycogen Storage Disease Glycogen Storage Disease Type Dietary Management Mitochondrial Fatty Acid Oxidation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Fasting intolerance


Glycogen storage disease


Ketone bodies


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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Irene J. Hoogeveen
    • 1
  • Rixt M. van der Ende
    • 1
  • Francjan J. van Spronsen
    • 1
  • Foekje de Boer
    • 1
  • M. Rebecca Heiner-Fokkema
    • 1
    • 2
  • Terry G. J. Derks
    • 1
    Email author
  1. 1.Section of Metabolic DiseasesBeatrix Children’s Hospital, University of Groningen, University Medical Center GroningenGroningenThe Netherlands
  2. 2.Laboratory of Metabolic Diseases, Department of Laboratory MedicineUniversity of Groningen, University Medical Center GroningenGroningenThe Netherlands

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