Metabolic Myopathies

Abstract

IntroductionInborn errors of glycogen and fatty acid metabolism that cause exclusively or predominantly neuromuscular disorders are characterized by dynamic or static symptoms. Dynamic symptoms are acute, recurrent, reversible muscle dysfunctions, manifesting as exercise intolerance, myalgia with or without painful cramps (contractures), and often culminating in muscle breakdown and myoglobinuria. In contrast, static symptoms are manifested by fixed, often progressive weakness, sometimes simulating dystrophic or neurogenic processes ( Fig. 63.1).To understand glycogen and lipid storage disorders, a brief review of muscle metabolism at rest and during exercise is helpful.The "fuel" utilized by muscle depends on several factors, most importantly the type, intensity, and duration of exercise but also diet and physical conditioning. At rest, muscle utilizes predominantly fatty acids. At the opposite end of the spectrum, the energy for extremely intense exercise (close to one's maximal oxygen uptake, or VO 2 max, in dynamic exercise or close to maximal force generation in isometric exercise) derives from anaerobic glycolysis, especially when there is a "burst" of activity with rapid acceleration to maximal exercise. During submaximal exercise, the type of fuel utilized by muscle depends on the relative intensity of exertion. At low intensity (below 50 % VO 2 max), blood glucose and free fatty acids (FFA) are the primary sources of energy. At higher intensities, the proportion of energy derived from carbohydrate oxidation increases, and muscle glycogen becomes an important fuel; at 70-80 % VO 2 max, aerobic metabolism of glycogen is the crucial source of energy, and fatigue appears to set in when glycogen is exhausted. The type of circulating substrate utilized during mild exercise varies with time, and there is a gradual increase in the utilization of FFA over glucose until, a few hours into