Muscle glycogen synthesis and breakdown are both impaired in glycogenin-1 deficiency

Neurology. 2017 Dec 12;89(24):2491-2494. doi: 10.1212/WNL.0000000000004752. Epub 2017 Nov 15.

Abstract

Objective: To study fat and carbohydrate metabolism during exercise in patients with glycogenin-1 (GYG1) deficiency, and to study whether IV glucose supplementation can alleviate exercise intolerance in these patients.

Methods: This is a case-control study with 4 patients with GYG1 deficiency and 4 healthy controls. Patients performed 1 hour of cycling at 50% of their maximal workload capacity, while controls cycled at the same absolute workloads as patients. Heart rate was measured continuously, and production and utilization of fat and glucose was assessed by stable isotope technique. The following day, patients repeated the exercise, this time receiving an IV 10% glucose supplement.

Results: Glucose utilization during exercise was similar in patients and controls, while palmitate utilization was greater in patients compared to controls. However, exercise-induced increases in lactate were attenuated to about half normal in patients. This was also the case during a handgrip exercise test. Glucose infusion improved exercise tolerance in patients, and lowered heart rate by on average 11 beats per minute during exercise.

Conclusions: The findings suggest that patients with GYG1 deficiency not only have abnormal formation of glycogen, but also have impaired muscle glycogenolysis, as suggested by impaired lactate production during exercise and improved exercise tolerance with glucose infusion.

MeSH terms

  • Administration, Intravenous
  • Adult
  • Aged
  • Carbohydrate Metabolism*
  • Case-Control Studies
  • Exercise Tolerance*
  • Exercise*
  • Female
  • Glucose / metabolism*
  • Glucose / therapeutic use
  • Glucosyltransferases / deficiency*
  • Glycogen / biosynthesis*
  • Glycogenolysis*
  • Glycoproteins / deficiency*
  • Heart Rate
  • Humans
  • Lactic Acid / metabolism
  • Lipid Metabolism*
  • Male
  • Middle Aged
  • Muscle, Skeletal / metabolism*
  • Palmitates / metabolism

Substances

  • Glycoproteins
  • Palmitates
  • glycogenin
  • Lactic Acid
  • Glycogen
  • Glucosyltransferases
  • Glucose