ABSTRACT: Purpose of Review: Metabolic myopathies are genetic disorders that impair intermediary metabolism in skeletal muscle. Impairments in glycolysis/glycogenolysis (glycogen-storage disease), fatty acid transport and oxidation (fatty acid oxidation defects), and the mitochondrial respiratory chain (mitochondrial myopathies) represent the majority of known defects. The purpose of this review is to develop a diagnostic and treatment algorithm for the metabolic myopathies.
Recent Findings: The metabolic myopathies can present in the neonatal and infant period as part of more systemic involvement with hypotonia, hypoglycemia, and encephalopathy; however, most cases present in childhood or in adulthood with exercise intolerance (often with rhabdomyolysis) and weakness. The glycogen-storage diseases present during brief bouts of high-intensity exercise, whereas fatty acid oxidation defects and mitochondrial myopathies present during a long-duration/low-intensity endurance-type activity or during fasting or another metabolically stressful event (eg, surgery, fever). The clinical examination is often normal between acute events, and evaluation involves exercise testing, blood testing (creatine kinase, acylcarnitine profile, lactate, amino acids), urine organic acids (ketones, dicarboxylic acids, 3-methylglutaconic acid), muscle biopsy (histology, ultrastructure, enzyme testing), MRI/spectroscopy, and targeted or untargeted genetic testing.
Summary: Accurate and early identification of metabolic myopathies can lead to therapeutic interventions with lifestyle and nutritional modification, cofactor treatment, and rapid treatment of rhabdomyolysis.
Address correspondence to Dr Mark A. Tarnopolsky, Division of Neuromuscular and Neurometabolic Disorders, McMaster University, 1200 Main St W, HSC-2H26, Hamilton, ON L8N 3Z5, Canada, email@example.com.
Relationship Disclosure: Dr Tarnopolsky has received personal compensation as a speaker and consultant for Sanofi Genzyme and has received research funding from the Canadian Institutes of Health Research, Exerkine Corporation, and MitoCanada. Dr Tarnopolsky is also a shareholder and stockholder for Exerkine Corporation.
Unlabeled Use of Products/Investigational Use Disclosure: Dr Tarnopolsky discusses the unlabeled/investigational use of triheptanoin, which is under license and investigation by Ultragenyx Pharmaceutical, Inc, to treat fatty acid oxidation defects.