title: Normoglycemic Ketonemia as Biochemical Presentation in Ketotic Glycogen Storage Disease.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Section of Metabolic Diseases, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, 30 001, 9700 RB, Groningen, The Netherlands.
authors.forename: Irene J
authors.initials: IJ
authors.lastname: Hoogeveen
authors.affiliation: Section of Metabolic Diseases, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, 30 001, 9700 RB, Groningen, The Netherlands.
authors.forename: Rixt M
authors.initials: RM
authors.lastname: van der Ende
authors.affiliation: Section of Metabolic Diseases, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, 30 001, 9700 RB, Groningen, The Netherlands.
authors.forename: Francjan J
authors.initials: FJ
authors.lastname: van Spronsen
authors.affiliation: Section of Metabolic Diseases, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, 30 001, 9700 RB, Groningen, The Netherlands.
authors.forename: Foekje
authors.initials: F
authors.lastname: de Boer
authors.affiliation: Section of Metabolic Diseases, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, 30 001, 9700 RB, Groningen, The Netherlands.|Laboratory of Metabolic Diseases, Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: M Rebecca
authors.initials: MR
authors.lastname: Heiner-Fokkema
authors.affiliation: Section of Metabolic Diseases, Beatrix Children's Hospital, University of Groningen, University Medical Center Groningen, 30 001, 9700 RB, Groningen, The Netherlands. t.g.j.derks@umcg.nl.
authors.forename: Terry G J
authors.initials: TG
authors.lastname: Derks