Endocrine Abstracts

Background/Introduction: The primary metabolic defect in glycogen storage disease type I (GSDI) results in fasting hypoglycemia and typical secondary metabolic abnormalities (e.g. hypertriglyceridemia, hyperlactatemia, hyperuricemia). The aim of this study was to broadly assess further perturbations of the metabolic network in GSDI by using untargeted plasma metabolomics.

Methods: Plasma samples of 14 adult GSDI patients (11 GSDIa, 3 GSDIb. Mean age 26.4 y, range 16–46 y) on standard treatment were compared to a cohort of 31 healthy controls utilizing ultra-high performance liquid chromatography (UHPLC) in combination with high resolution tandem mass spectrometry (HR-MS/MS) and subsequent statistical multivariate analysis. Significantly altered features were identified by mining against an internal library as well as online databases Metlin and mzCloud.

Results: The metabolic profile showed numerous alterations of metabolites in different areas of the metabolic network, e.g. in central pathways of energy generation such as the tricarboxylic acid cycle, in the metabolism of creatine, in the urea cycle, in the amino acid and purine/pyrimidine metabolism, but also changes of enzyme cofactors such as biotin. These metabolic alterations were consistently seen in patients of both GSD subtypes (Ia and Ib).

Conclusion: The metabolic defect of GSDI has profound effects on a variety of metabolic pathways in both GSDI subtypes, in addition to the known typical metabolic abnormalities (e.g. in lipid metabolism). The effect of glycemic control on these metabolic alterations, as well as the mechanisms behind these observations remain to be further elucidated.