Journal Article

Riboflavin-responsive lipid-storage myopathy caused by ETFDH gene mutations

Liu, Shuping, Dai, Tingjun, Li, Honghao, Yan, Chuanzhu, Zhao, Yuying, Li, Wei, Li, Danian, Wen, Bing, Zhang, Chunhua, Wu, Jinling

2010

Overview

BackgroundLipid-storage myopathy (LSM), defined by triglyceride accumulation in muscle fibres, is a heterogeneous group of lipid metabolic disorders predominantly affecting skeletal muscle. In the past 15 years, more than 200 cases of LSM have been reported in the Chinese literature, but the accurate pathogenic mechanisms are still unknown.ObjectiveIn order to gain more insight into the metabolic and genetic dysfunctions of LSM, the authors described a group of Chinese patients with LSM who were very responsive to isolated riboflavin treatment (riboflavin responsive LSM, RR-LSM).MethodsNineteen consecutive LSM patients collected during 1995–2007 in our Neuromuscular Laboratory who were dramatically responsive to riboflavin and presented with proximal muscle weakness, exercise intolerance and elevated serum CK but without episodic encephalopathy were subjected to pathological, biochemical and molecular analysis.ResultsOn the basis of muscle pathology, all 19 patients were diagnosed as LSM. Seventeen patients were suspected of having multiple acyl-coenzyme A dehydrogenase deficiency (MADD) according to blood acylcarnitine profiles and urine organic acid analysis. Genetic analysis identified 19 novel mutations in ETFDH gene in 18 patients, among which one was homozygote, 16 were compound heterozygotes, and one was a single heterozygote. No pathogenic mutation was detected in ETFA or ETFB genes. Western blot analysis showed there was no significant decrease in ETF:QO expression except for one patient.ConclusionsThe research findings suggest that the majority of Chinese patients with RR-LSM are caused by a mild type of MADD with unique myopathy which is due to ETFDH gene mutation.

• Publisher: BMJ Publishing Group Ltd,BMJ Publishing Group,BMJ Publishing Group LTD
• Subject: Adolescent / Adult / Biological and medical sciences / Biopsy / Blotting, Western / Child / Dehydrogenases / Diseases of striated muscles. Neuromuscular diseases / Electron-Transferring Flavoproteins - genetics / ETFDH / Female / Genes / Humans / Iron-Sulfur Proteins - genetics / Laboratories / Lipase / Lipid Metabolism Disorders - drug therapy / Lipid Metabolism Disorders - genetics / Lipid Metabolism Disorders - metabolism / lipid storage myopathy / Lipids / Male / Mass spectrometry / Medical sciences / metabolic disease / Metabolism / Middle Aged / Multiple Acyl Coenzyme A Dehydrogenase Deficiency - genetics / Multiple Acyl Coenzyme A Dehydrogenase Deficiency - metabolism / multiple acyl-coenzyme A dehydrogenase deficiency / Muscle Weakness / Muscle, Skeletal - metabolism / Muscle, Skeletal - pathology / Muscular Diseases - drug therapy / Muscular Diseases - genetics / Muscular Diseases - metabolism / Muscular Diseases - pathology / Mutation / myopathy / Neurology / Oxidation / Oxidoreductases Acting on CH-NH Group Donors - genetics / Patients / Point Mutation - genetics / Proteins / riboflavin / Riboflavin - therapeutic use / Scientific imaging / Urine / Vitamin B / Young Adult