Untargeted plasma metabolomics identifies broad metabolic perturbations in glycogen storage disease type I

Mathis Tamara,Poms Martin,Baumgartner Matthias,Michel Hochuli,Gautschi Matthias,Plecko Barbara

doi:10.1530/endoabs.70.aep309

Abstract

Untargeted plasma metabolomics identifies broad metabolic perturbations in glycogen storage disease type I

Highlights

Glycogen storage disease type I (GSDI, van Gierke’s disease OMIM 232200) is an inherited metabolic disorder resulting from a defect of either glucose-6-phosphatase-α (GSDIa) or the glucose-6phosphate-transporter (GSDIb), translocating glucose-6-phosphate into the lumen of the endoplasmic reticulum for hydrolysis by glucose-6-phosphatase
The metabolic defect of glycogen storage disease type I (GSDI) has profound effects on a variety of metabolic pathways in addition to the known typical abnormalities. These alterations are present despite optimized dietary treatment, which may contribute to the risk of developing long-term complications, an inherent problem of GSDI which appears to be only partly modified by current therapy
Take-home message: The metabolic defect of GSDI has profound effects on a variety of metabolic pathways which appear to be only partly modified by standard treatment, and are independent of the presence or absence of complications

Summary

Introduction

Glycogen storage disease type I (GSDI, van Gierke’s disease OMIM 232200) is an inherited metabolic disorder resulting from a defect of either glucose-6-phosphatase-α (GSDIa) or the glucose-6phosphate-transporter (GSDIb), translocating glucose-6-phosphate into the lumen of the endoplasmic reticulum for hydrolysis by glucose-6-phosphatase. Hepatic cytoplasmic accumulation of glucose-6-phosphate and subsequent increases of other phosphomonoesters (i.e. glycolytic intermediates) trigger a series of changes in metabolic fluxes, such as enhanced glycolytic flux with production of excessive lactate, and markedly increased hepatic de novo lipogenesis (from increased availability of substrates, and by increased expression and activity of lipogenic transcription factors) with profound changes in lipid metabolism and liver steatosis (Greene et al 1978; Greene et al 1979; Oberhaensli et al 1988; Bandsma et al 2002; Bandsma et al 2008; Derks and van Rijn 2015; Cho et al 2018; Hornemann et al 2018). The aim of this study was to assess further perturbations of the metabolic network in GSDI patients under ongoing treatment

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