In a safe training protocol for GSD V patients that acts under consideration of the deficiency in glycogenolyisis, the duration of exercise must be short enough to avoid deep PCr depletion and a degeneration of ATP pool. Recovery periods must be long enough to allow a full PCr resynthesis. Ketogenic diet is a special high fat, carbohydrate-restricted diet, which Inhibitors,research,lifescience,medical was developed in 1921 at the Mayo Clinic. It reproduces the metabolic effects of fasting when ketone bodies from fatty acids become a significant energy source for extra
hepatic tissues. The typical isocaloric diet provides fat and protein plus carbohydrate in a ratio of 4:1. Very careful calculation of nutrient composition has to be combined with a very restrictive and demanding Inhibitors,research,lifescience,medical medical and
nutritional supervision during the study. Ketogenic diet has proven to be effective in difficult-to-treat refractory epilepsies, as well as in inborn errors of brain energy metabolism. McArdle patients are not able to mobilize glycogen and have impaired oxidative phosphorylation. We suspected that the replacement of glucose by ketone bodies might Inhibitors,research,lifescience,medical reduce the glycogen synthesis and to some extent replete the tricarboxylic acid cycle with acetyl-CoA. We replaced the energy substrate glucose by ketone bodies using the ketogenic diet in a 55 year-old man with McArdle disease. By increasing the fat content of his diet to 80% with 14% protein (1 g/kg/d) to totally 1.760 kcal, ketosis of 2-6 mmol/l 3-OH-butyrate Inhibitors,research,lifescience,medical was established. The principal effects comprise absence of carbohydrate-based stimulation of insulin secretion leading to activation of glycogen synthesis, and
repletion of the tricarboxylic cycle with acetyl-CoA Inhibitors,research,lifescience,medical from ketone bodies. With a continuous NVP-AEW541 supplier one-year diet his exercise tolerance was 3- to 10-fold increased dependent of the endurance level. Maximum strength and activity duration also improved and CK levels dropped from 5.300 U/l to 890 U/l on ketogenic diet. However, ketogenic diet did not distinctly change 31PMRS data during rest, work, however and recovery. The beneficial effect of ketogenic diet in an individual patient study seems promising, but truly needs to be verified in further trials with standardised assessment protocols (25).
Glycogen storage disease type II has a broad continuous clinical spectrum in terms of onset, involvement of organs and life expectancy. Infantile onset is the most severe form, presenting with prominent cardiomyopathy, hypotonia, hepatomegaly and death before 12 months of life. Late onset form has onset at any age, lack of severe (or absence of) cardiac involvement, progressive skeletal muscle dysfunction and less dismal short-term prognosis. In addition to muscle and heart involvement, other tissues are affected liver, spleen, endothelium, lung, brain, anterior horns, peripheral nerves.