Lipid Storage Myopathy

Abstract

Lipid storage myopathy (LSM) is pathologically characterized by prominent lipid accumulation in muscle fibers due to lipid dysmetabolism. Although extensive molecular studies have been performed, there are only four types of genetically diagnosable LSMs: primary carnitine deficiency (PCD), multiple acyl-coenzyme A dehydrogenase deficiency (MADD), neutral lipid storage disease with ichthyosis, and neutral lipid storage disease with myopathy. Making an accurate diagnosis, by specific laboratory tests including genetic analyses, is important for LSM as some of the patients are treatable: individuals with PCD show dramatic improvement with high-dose oral L-carnitine supplementation and increasing evidence indicates that MADD due to ETFDH mutations is riboflavin responsive.

A case of late-onset riboflavin responsive multiple acyl-CoA dehydrogenase deficiency (MADD) with a novel mutation in ETFDH gene

“…Although the molecular mechanism of MADD is still unclear, riboflavin (or vitamin B2) supplementation (100-400 mg/d) has been known to strikingly improve the clinical symptoms and metabolism disorder of MADD patients, particularly those with the late-onset form [11]. The results with combination therapy by carnitine and coenzyme Q10 are still controversial.…”

Amelioration of acylcarnitine profile using bezafibrate and riboflavin in a case of adult-onset glutaric acidemia type 2 with novel mutations of the electron transfer flavoprotein dehydrogenase (ETFDH) gene

“…In the present case, oral carnitine alone leads to only partial improvement based on amelioration of the patient's muscle weakness and decreases in his serum CK and acyl-CoA. Riboflavin supplementation produces improvements in the symptoms and metabolic profiles of GA2 patients with ETFDH mutations, and the late-onset form [2]. BEZ is a hypolipidemic drug that is as an agonist of the peroxisome proliferating activator receptor, and was found to be beneficial in Japanese children with ETFDH gene mutations exhibiting GA2 [5].…”

“…GA2 is a rare autosomal recessive disorder whose biochemical abnormalities result from a deficiency of one of the two electron transfer flavoproteins (ETF and ETFDH) that transfer electrons from acyl-CoA dehydrogenases to the respiratory chain [2]. The disorder affects multiple metabolic pathways involving branched amino acids, fatty acids, and tryptophan, and results in a variety of distinctive organic acids being discharged.…”

A 61-Year-Old Woman with Muscle Fatigue and Increased Cardiac Troponin

“…Lipid storage myopathy has a relatively short differential diagnosis and includes primary carnitine deficiency, multiple acyl-CoA dehydrogenase deficiency (MADD, otherwise known as glutaric aciduria type II) and neutral lipid storage disorders (2 ). The patient's plasma acylcarnitine profile demonstrated increased C4-C18 acylcarnitine species, and urine organic acid analysis revealed moderate increases of adipic, ethylmalonic, and 2-hydroxyglutaric acids with a small increase of hexanoylglycine.…”