Metabolic myopathies comprise a broad group of disorders caused by defects in the biochemical pathways that produce adenosine triphosphate (ATP)(DiMauro S et al., 2004). It is not surprising that defects of ATP synthesis cause diseases of muscle because this tissue consumes large amounts of energy. The concept of metabolic myopathy originated in 1951 with Dr. Brian McArdle's description of a patient with ischemic exercise-induced painful muscle contractures without electrical activity by electromyography (McArdle B, 1951). McArdle noted that the patient's venous lac-tate and pyruvate did not rise after exercise; therefore, he correctly deduced that the disorder was due to a defect in glycogen conversion to lactate. Nine years later, deficiency of myophosphorylase, a muscle-specific enzyme that catalyzes the first step of glycogen breakdown, was identified as the cause of McArdle disease. In 1962, Dr. Rolf Luft reported the first mitochondria! myopathy patient —a young woman with severe hypermetabolism and normal thyroid function (Luft R et al., 1962). Ultrastructural analyses revealed massive proliferation of mitochondria while biochemical studies revealed loose coupling between oxygen consumption and phosphorylation (ATP synthesis) in isolated mitochondria from muscle. In 1973, Dr. Salvatore DiMauro identified the first myopathy due to a defect in fatty acid metabolism in two brothers with recurrent myoglobin-uria and deficiency of carnitine palmitoyltransferase (CPT)(DiMauro S and DiMauro-Melis PM, 1973). At that time, activities of CPT I and CPT II could not be distinguished, but subsequently, this disease was linked to CPT II deficiency. These three seminal papers described the first defects of glycogen metabolism, mitochondrial oxidative phosphorylation, and fatty acid metabolism; dysfunction of these three biochemical pathways are responsible for the vast majority of metabolic myopathies.
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