Clinical and genetic analysis of lipid storage myopathies.
Causative genes have been identified only in four types of lipid storage myopathies (LSMs): SLC22A5 for primary carnitine deficiency (PCD); ETFA, ETFB, and ETFDH for multiple acyl-coenzyme A dehydrogenation deficiency (MADD); PNPLA2 for neutral lipid storage disease with myopathy (NLSDM); and ABHD5 for neutral lipid storage disease with ichthyosis. However, the frequency of these LSMs has not been determined. We found mutations in only 9 of 37 LSM patients (24%): 3 in SLC22A5; 4 in MADD-associated genes; and 2 in PNPLA2. This low frequency suggests the existence of other causative genes. Muscle coenzyme Q(10) levels were normal or only mildly reduced in two MADD patients, indicating that ETFDH mutations may not always be associated with CoQ(10) deficiency. The 2 patients with PNPLA2 mutations had progressive, non-episodic muscle disease with rimmed vacuoles. This suggests there is a different pathomechanism from other LSMs.
Ohkuma
Aya
A
Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawahigashi-cho, Kodaira, 187-8502 Tokyo, Japan.
Noguchi
Satoru
S
Sugie
Hideo
H
Malicdan
May Christine V
MC
Fukuda
Tokiko
T
Shimazu
Kunio
K
López
Luis Carlos
LC
Hirano
Michio
M
Hayashi
Yukiko K
YK
Nonaka
Ikuya
I
Nishino
Ichizo
I
D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002855:Chromatography, Thin Layer / Q000379:methods; D004252:DNA Mutational Analysis; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000235:genetics; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006801:Humans; D007223:Infant; D008049:Lipase / Q000235:genetics; D050356:Lipid Metabolism; D052439:Lipid Metabolism Disorders / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000473:pathology / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000150:complications* / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D027701:Organic Cation Transport Proteins / Q000235:genetics; D012189:Retrospective Studies; D000074058:Solute Carrier Family 22 Member 5; D055815:Young Adult; D000217:Acyltransferases
D053418:Death Domain Receptor Signaling Adaptor Proteins; D020662:Guanine Nucleotide Exchange Factors; D008049:Lipase; D027701:Organic Cation Transport Proteins; D000074058:Solute Carrier Family 22 Member 5; C105852:MADD protein, human; C492020:SLC22A5 protein, human; C494794:PNPLA2 protein, human; D000217:Acyltransferases