Submitted on December 3, 2006
Accepted on August 28, 2007
Characterization of hepatic and brain metabolism in young adults with glycogen storage disease type I. A magnetic resonance spectroscopy study
Daniel Weghuber1, Martina Mandl2, Martin Krssak3, Michael Roden4, Peter Nowotny2, Attila Brehm2, Michael Krebs2, Kurt Widhalm5, and Martin G. Bischof6*
1 Department of Pediatrics, Medical University Vienna, Vienna, Austria; Department of Pediatrics, Paracelsus Private Medical School Salzburg, Salzburg, Austria
2 Department of Internal Medicine III, Division of Endocrinology and Metabolism, Medical University Vienna, Vienna, Austria
3 Department of Internal Medicine 3, University of Vienna, A-1090 Wien, Austria
4 Department of Internal Medicine I, Hanusch Hospital, Vienna A1140, Austria
5 Department of Pediatrics, Medical University Vienna, Vienna, Austria
6 Department of Internal Medicine III, University of Vienna, Vienna, Austria
* To whom correspondence should be addressed. E-mail: martin.bischof{at}meduniwien.ac.at.
In glycogen storage disease type 1 (GSD1) children present with severe hypoglycemia while the propensity for hypoglycemia may decrease with age in these patients. It was the aim of this study to elucidate the mechanisms for milder hypoglycemia symptoms in grown up GSD1 patients. Four patients with GSD1 (Body mass index (BMI) 23.2±6.3 kg·m-2, age 21.3±2.9 years) and four healthy controls matched for BMI (23.1±3 kg·m-2) and age (24±3.1 years) were studied. Combined 1H/31P nuclear magnetic resonance spectroscopy (NMRS) was used to assess brain metabolism. Before and after administration of 1 mg glucagon endogenous glucose production (EGP) was measured with D-[6,6-2H2]glucose while hepatic glucose metabolism was examined by 1H/13C/31P NMRS. At baseline GSD1 patients exhibited significantly lower rates of EGP (0.53±0.04 vs. 1.74±0.03 mg·kg-1·min-1, p<0.01 vs. control) but an increased intrahepatic glycogen (502±89 vs. 236±11 mmol/l, p=0.05 vs. control) and lipid content (16.3±1.1 vs. 1.4±0.4 %, p<0.001 vs. control). After glucagon challenge, EGP did not change in GSD1 patients (0.53±0.04 vs. 0.59±0.24 mg·kg-1·min-1; p=n.s.) but increased in healthy controls (1.74±0.03 vs. 3.95±1.34, p<0.0001). In GSD1 patients we found an exaggerated increase of intrahepatic phosphomonoesters (0.23±0.08 vs. 0.86±0.19AU, p<0.001) while inorganic phosphate even decreased (0.36±0.08 vs. -0.43±0.17 AU, p<0.01). Intracerebral ratios of glucose, glutamate, and myo-inositol:creatine were higher in GSD1 patients (p<0.05 vs. control, respectively). Hepatic defects of glucose metabolism persist in grown up GSD1 patients. Upregulation of the glucose and lactate transport at the blood-brain barrier could be responsible for the amelioration of hypoglycemic symptoms.
