Riboflavin-responsive lipid-storage myopathy caused by ETFDH gene mutations.
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.
Wen
Bing
B
Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, PR China.
Dai
Tingjun
T
Li
Wei
W
Zhao
Yuying
Y
Liu
Shuping
S
Zhang
Chunhua
C
Li
Honghao
H
Wu
Jinling
J
Li
Danian
D
Yan
Chuanzhu
C
D000293:Adolescent; D000328:Adult; D015153:Blotting, Western; D002648:Child; D044927:Electron-Transferring Flavoproteins / Q000235:genetics*; D005260:Female; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000235:genetics*; D008049:Lipase; D052439:Lipid Metabolism Disorders / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D054069:Multiple Acyl Coenzyme A Dehydrogenase Deficiency / Q000235:genetics* / Q000378:metabolism; D018908:Muscle Weakness; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D012256:Riboflavin / Q000627:therapeutic use*; D055815:Young Adult
D044927:Electron-Transferring Flavoproteins; D007506:Iron-Sulfur Proteins; D000587:Oxidoreductases Acting on CH-NH Group Donors; C023120:electron-transferring-flavoprotein dehydrogenase; D008049:Lipase; D012256:Riboflavin