Cardiopulmonary Exercise Testing and Metabolic Myopathies.

Skeletal muscle requires a large increase in its ATP production to meet the energy needs of exercise. Normally, most of this increase in ATP is supplied by the aerobic process of oxidative phosphorylation. The main defects in muscle metabolism that interfere with production of ATP are (1) disorders of glycogenolysis and glycolysis, which prevent both carbohydrate entering the tricarboxylic acid cycle and the production of lactic acid; (2) mitochondrial myopathies where the defect is usually within the electron transport chain, reducing the rate of oxidative phosphorylation; and (3) disorders of lipid metabolism. Gas exchange measurements derived from exhaled gas analysis during cardiopulmonary exercise testing can identify defects in muscle metabolism because [Formula: see text]o and [Formula: see text]co are abnormal at the level of the muscle. Cardiopulmonary exercise testing may thus suggest a likely diagnosis and guide additional investigation. Defects in glycogenolysis and glycolysis are identified by a low peak [Formula: see text]o and absence of excess [Formula: see text]co from buffering of lactic acid by bicarbonate. Defects in the electron transport chain also result in low peak [Formula: see text]o, but because there is an overreliance on anaerobic processes, lactic acid accumulation and excess carbon dioxide from buffering occur early during exercise. Defects in lipid metabolism result in only minor abnormalities during cardiopulmonary exercise testing. In defects of glycogenolysis and glycolysis and in mitochondrial myopathies, other features may include an exaggerated cardiovascular response to exercise, a low oxygen-pulse, and excessive ammonia release.