title: Clinical and genetic analysis of lipid storage myopathies.
abstract: 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.
authors.affiliation: 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.
authors.forename: Aya
authors.initials: A
authors.lastname: Ohkuma
authors.forename: Satoru
authors.initials: S
authors.lastname: Noguchi
authors.forename: Hideo
authors.initials: H
authors.lastname: Sugie
authors.forename: May Christine V
authors.initials: MC
authors.lastname: Malicdan
authors.forename: Tokiko
authors.initials: T
authors.lastname: Fukuda
authors.forename: Kunio
authors.initials: K
authors.lastname: Shimazu
authors.forename: Luis Carlos
authors.initials: LC
authors.lastname: López
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
authors.forename: Yukiko K
authors.initials: YK
authors.lastname: Hayashi
authors.forename: Ikuya
authors.initials: I
authors.lastname: Nonaka
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
mesh_terms: 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
chemical_list: 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