Riboflavin-responsive lipid-storage myopathy caused by ETFDH gene mutations
- Bing Wen1,
- Tingjun Dai1,
- Wei Li1,
- Yuying Zhao1,
- Shuping Liu1,
- Chunhua Zhang2,
- Honghao Li1,
- Jinling Wu1,
- Danian Li1,
- Chuanzhu Yan1,3
- 1Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, PR China
- 2Department of research and development, MILS International, Kanazawa, Japan
- 3The Key Laboratory for Experimental Teratology of the Ministry of Education and Institute of Medical Genetics, School of Medicine, Shandong University, Jinan, PR China
- Correspondence to Dr C Yan, No 107, West Wenhua Road, Jinan, PR China, 250012;
- Received 25 February 2009
- Revised 4 August 2009
- Accepted 26 August 2009
- Published Online First 15 September 2009
Background Lipid-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.
Objective In 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).
Methods Nineteen 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.
Results On 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.
Conclusions The 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.
- lipid storage myopathy
- multiple acyl-coenzyme A dehydrogenase deficiency
- metabolic disease
A supplementary figure is published online only at http://journal.bmj.com/content/vol81/issue2
Funding Natural Science Foundation of Shandong Province, PR China (grant no Y2002C34) and National Natural Science Foundation of China (grant no.30970993).
Competing interests None.
Ethics approval Ethics approval was provided by the medical Ethics Committee of Qilu Hospital.
Patient consent Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.