Metabolic Myopathies

Abstract

Metabolic myopathies are inborn errors of metabolism that impair the metabolism of substrates and result in exercise intolerance. Fatty acid oxidation defects (FAODs), glycogen storage disease (GSD), and mitochondrial myopathies represent the three main groups of disorders, and some consider myoadenylate deaminase deficiency (AMPD1) to be a metabolic myopathy. In general, the GSDs result in high-intensity exercise intolerance, whereas the FAODs and the mitochondrial myopathies manifest predominantly during endurance type activity or under fasted or other metabolically stressful conditions. The clinical examination is often normal, and testing requires various combinations of exercise stress testing, serum creatine kinase (CK) activity and lactate concentration determination, urine organic acids, muscle biopsy, and specific genetic testing. Prenatal screening is available in many countries for the more severe FAODs via liquid chromatography-tandem mass spectrometry. Early identification of these conditions with lifestyle measures, nutritional intervention, and cofactor treatment is important to avoid potential life-threatening complications such as severe rhabdomyolysis with resultant renal failure.