Investigation of metabolic myopathies

Publisher Summary This chapter presents the investigation of metabolic myopathies. Glycogen storage disorders (the glycogenoses) are a group of rare inherited metabolic diseases due to abnormal synthesis or breakdown of glycogen. Most affect single cytoplasmic enzymes, with the exception of α-glucosidase (acid maltase) deficiency which involves the lysosomal glycogen degradation pathway. The glycogen storage disorders generally present clinically in one of two ways: exercise intolerance, muscle cramps and intermittent rhabdomyolysis, or progressive proximal weakness. Defects of mitochondrial oxidative phosphorylation are an important cause of muscle disease and are often described as mitochondrial myopathies. The biochemistry and genetics of these disorders are much more complex than either glycogen storage disorders or fatty acid oxidation, predominantly due to the involvement of the mitochondrial genome (mtDNA). In addition, mitochondrial oxidative phosphorylation disorders — all of which are characterized by the inability of the cell to produce enough ATP on account of respiratory chain dysfunction—may present with a vast array of different clinical features, which makes them enter the differential diagnosis of many different neurological conditions.