Normoglycemic Ketonemia as Biochemical Presentation in Ketotic Glycogen Storage Disease
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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.
KeywordsPlasma Glucose Concentration Glycogen Storage Disease Glycogen Storage Disease Type Dietary Management Mitochondrial Fatty Acid Oxidation
Glycogen storage disease
- Dagli A, Weinstein D (2009) Glycogen storage disease type VI. In: Pagon RA, Adam MP, Ardinger HH et al (eds) GeneReviews. University of Washington, SeattleGoogle Scholar
- Dagli A, Sentner C, Weinstein D (2010) Glycogen storage disease type III. In: Pagon RA, Adam MP, Ardinger HH et al (eds) GeneReviews. University of Washington, SeattleGoogle Scholar
- Goldstein J, Austin S, Kishnani P et al (2011) Phosphorylase kinase deficiency. In: Pagon RA, Adam MP, Ardinger HH et al (eds) GeneReviews. University of Washington, SeattleGoogle Scholar
- Laforêt P, Weinstein DA, Smit GPA (2012) The glycogen storage diseases and related disorders. In: Saudubray JM, van de Berghe G, Walter J (eds) Inborn metabolic diseases: diagnosis and treatment. Springer, BerlinGoogle Scholar
- Seigel J, Weinstein DA, Hillman R, Colbert B, Matthews B, Bachrab B (2008) Glycogen storage disease type IIIa presenting as non-ketotic hypoglycemia: use of a newly approved commercially available mutation analysis to non-invasively confirm the diagnosis. J Pediatr Endocrinol Metab 6:587–590Google Scholar
- Touati G, Mochel F, Rabier D (2012) Diagnostic procedures: functional tests and post-mortem protocol. In: Saudubray JM, van den Berghe G, Walter J (eds) Inborn metabolic diseases: diagnosis and treatment. Springer, BerlinGoogle Scholar