Neutral lipid storage disease with subclinical myopathy due to a retrotransposal insertion in the PNPLA2 gene.
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.
Akman
Hasan O
HO
Department of Neurology, Columbia University Medical Center, New York, NY, USA.
Davidzon
Guido
G
Tanji
Kurenai
K
Macdermott
Emma J
EJ
Larsen
Louann
L
Davidson
Mercy M
MM
Haller
Ronald G
RG
Szczepaniak
Lidia S
LS
Lehman
Thomas J A
TJ
Hirano
Michio
M
DiMauro
Salvatore
S
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
D004247:DNA; D008049:Lipase; D012333:RNA, Messenger; C494794:PNPLA2 protein, human; D000217:Acyltransferases
Proc Natl Acad Sci U S A. 1989 Apr;86(7):2379-82
2928337
Neuromuscul Disord. 2008 Aug;18(8):671-4
18657972
Nature. 1998 Jul 23;394(6691):388-92
9690476
J Inherit Metab Dis. 2003;26(2-3):147-69
12889657
Nat Genet. 2007 Jan;39(1):28-30
17187067
Muscle Nerve. 1979 Jan-Feb;2(1):1-13
545139
Arch Neurol. 2005 Nov;62(11):1709-12
16286544
J Biol Chem. 2004 Oct 1;279(40):42062-71
15292255
Neurology. 2006 Jan 24;66(2):253-5
16434667
Biochem Biophys Res Commun. 2008 Dec 19;377(3):843-6
18952067
Am J Hum Genet. 2001 Nov;69(5):1002-12
11590543
Biochem Biophys Res Commun. 2008 May 16;369(4):1125-8
18339307
Methods Cell Biol. 2001;65:311-32
11381601
Neurology. 1997 May;48(5):1238-43
9153450
Blood. 1966 Aug;28(2):258-65
5330405
Trends Genet. 2007 Apr;23(4):183-91
17331616
Arch Neurol. 2005 Feb;62(2):317-20
15710863
Muscle Nerve. 2009 Mar;39(3):333-42
19208393
Neurology. 2001 Aug 14;57(3):515-8
11502923
Am J Physiol. 1999 May;276(5):E977-89
10329993
Muscle Nerve. 2007 Dec;36(6):856-9
17657808
Biochimie. 2005 Jan;87(1):45-9
15733736
Brain. 2007 Aug;130(Pt 8):2037-44
17412732
Science. 2004 Nov 19;306(5700):1383-6
15550674
J Biol Chem. 2005 May 13;280(19):19146-55
15731108