Lipid Myopathies

Abstract

Disorders of lipid metabolism affect several tissues, including skeletal and cardiac muscle tissues. Lipid myopathies (LM) are rare multi-systemic diseases, which most often are due to genetic defects. Clinically, LM can have acute or chronic clinical presentation. Disease onset can occur in all ages, from early stages of life to late-adult onset, showing with a wide spectrum of clinical symptoms. Muscular involvement can be fluctuant or stable and can manifest as fatigue, exercise intolerance and muscular weakness. Muscular atrophy is rarely present. Acute muscular exacerbations, resulting in rhabdomyolysis crisis are triggered by several factors. Several classifications of lipid myopathies have been proposed, based on clinical involvement, biochemical defect or histopathological findings. Herein, we propose a full revision of all the main clinical entities of lipid metabolism disorders with a muscle involvement, also including some those disorders of fatty acid oxidation (FAO) with muscular symptoms not included among previous lipid myopathies classifications.

Keywords: FAO defect; beta-oxidation defects; lipid metabolism disorders; lipid myopathies; lipid storage disease; metabolic myopathies; muscle lipidosis.

Figure 1

Metabolic pathway of lipid metabolism in muscle. ACDA9: Acyl-CoA dehydrogenase 9; ACS: Acetyl-CoA synthetase; ATGL: Adipose triglyceride lipase; CACT: Carnitine-acylcarnitine translocase; CGI58: Comparative gene identification-58; CPT I: Carnitine palmitoyl transferase I; CPT II: Carnitine palmitoyl transferase II; DECR: Dienoyl-CoA reductase; DG: Diglycerides; ECH: Enoyl-CoA hydratase; ETF: Electron transport flavoprotein; FABP: Fatty acid binding protein; FAD: flavin adenine dinucleotide; FADH: flavin adenine dinucleotide reduced; FATP1: Fatty acid transport protein 1; FFA: Free fatty acid; LCFAT: Long chain fatty acid; LCHAD: long-chain 3-hydroxyacyl-CoA dehydrogenase; LCKAT: long-chain 3-ketoacyl-CoA thiolase; LD: Lipid droplet; Lipin1-Lipin 1; MCAD: Medium-chain acyl-CoA dehydrogenase; MG: Monoglycerides; NAD: Nicotinamide adenin dinucleotide; NADH: Nicotinamide adenin dinucleotide reduced; OCTN2: Organic Cation/Carnitine Transporter 2; Q: Coenzyme Q; SCAD: Short-chain acyl-CoA dehydrogenase; VLCAD: Very-long-chain acyl-CoA dehydrogenase; TCA: tricarboxylic acid.

Figure 2

Massive lipidosis and Jordans’ anomaly. (A) Lipid storage in muscle fibers from NLSD-M patient; optic microscopy, Oil-red-O (ORO) stain, 20×. (B) Leucocyte presenting lipid droplets (Jordans’ anomaly); optic microscopy, Giemsa, 100×.