G.P.114 Exercise intolerance in Debrancher deficiency is caused by a block in skeletal muscle and liver glycogen breakdown

Abstract Debrancher deficiency is an inborn error of glycogen metabolism. Glycogen is an essential energy source for skeletal muscle during exercise and it is interesting that Debrancher deficiency is not associated with dynamic exercise induced symptoms. We hypothesized that in patients with Debrancher deficiency type IIIa, without significant weakness or muscle wasting, we would observe an exercise intolerance. The aim was to examine excercise tolerance in patients with Debrancher deficiency. Six patients (aged 15–37-years) were included. We determined peak work capacity, and the response to forearm exercise. We measured substrate metabolism during cycling exercise at 70% of VO2peak. Finally, in an attempt to circumvent the metabolic block and improve exercise tolerance, the patients were given a glucose infusion during constant load cycling. VO2peak was reduced below normal in all subjects (25.4 ml/kg/min, range; 16.1–29.6). In addition the rise in plasma lactate after peak exercise was only 1.7-fold and only 1.6-fold after forearm exercise. Cycling at 70% of VO2peak was not well tolerated and was associated with muscle pain and excessive fatigue, and a rapid development of hypoglycemia IV glucose infusion improved work capacity (heart rate during exercise was lowered to 131 bpm vs. 135 bpm with saline infusion, p  = 0.036), and the Wpeak was increased by 30% (108 Watts with glucose vs. 83 Watts with saline infusion, p  = 0.018). This is the first study to quantify exercise intolerance in Debrancher deficiency. We demonstrate that Debrancher deficiency is associated with exercise intolerance and dynamic exercise related symptoms not only as a consequence of a reduced glycogenolytic capacity in skeletal muscle, but also due to the liver involvement in this glycogen storage disease. Intravenous glucose infusion improves exercise tolerance and it seems likely that an oral glucose load, may have the same effect.