title: Neutral lipid storage disease with subclinical myopathy due to a retrotransposal insertion in the PNPLA2 gene.
abstract: An 18-year-old girl referred to a rheumatologist with malar flush and Gottran papules was found to have a markedly elevated serum CK. She was a good student and an avid ballet dancer. A muscle biopsy showed massive triglyceride storage, which was also found in peripheral blood granulocytes (Jordan anomaly) and cultured skin fibroblasts. Assessment using computerized dynamometry and cycle ergometry showed normal strength and muscle energetics, but proton spectroscopy revealed severe triglyceride accumulation in both skeletal and cardiac muscle. Sequencing of PNPLA2, the gene responsible for neutral lipid storage disease with myopathy (NLSDM), revealed a retrotransposal insertion of about 1.8kb in exon 3 that abrogates transcription of PNPLA2. The sequences of CGI-58, the gene responsible for Chanarin-Dorfman syndrome (CDS), another multisystem triglyceride storage disease, and of two genes encoding lipid droplets-associated proteins, perilipin A and adipophilin, were normal. This case shows that NLSDM can be a transposon-associated disease and that massive lipid storage in muscle can present as asymptomatic hyperCKemia.
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Hasan O
authors.initials: HO
authors.lastname: Akman
authors.forename: Guido
authors.initials: G
authors.lastname: Davidzon
authors.forename: Kurenai
authors.initials: K
authors.lastname: Tanji
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Macdermott
authors.forename: Louann
authors.initials: L
authors.lastname: Larsen
authors.forename: Mercy M
authors.initials: MM
authors.lastname: Davidson
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Haller
authors.forename: Lidia S
authors.initials: LS
authors.lastname: Szczepaniak
authors.forename: Thomas J A
authors.initials: TJ
authors.lastname: Lehman
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
authors.forename: Salvatore
authors.initials: S
authors.lastname: DiMauro
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D002648:Child; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005080:Exercise Test; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D006098:Granulocytes / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008049:Lipase / Q000235:genetics*; D052439:Lipid Metabolism Disorders / Q000150:complications / Q000235:genetics* / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008967:Molecular Biology; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012206:Rhabdomyolysis / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D046509:Tissue Culture Techniques; D014158:Transcription, Genetic; D000217:Acyltransferases
chemical_list: D004247:DNA; D008049:Lipase; D012333:RNA, Messenger; C494794:PNPLA2 protein, human; D000217:Acyltransferases
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