A novel mutation in PNPLA2 causes neutral lipid storage disease with myopathy and triglyceride deposit cardiomyovasculopathy: a case report and literature review.
Mutations in PNPLA2 cause neutral lipid storage disease with myopathy (NLSDM) or triglyceride deposit cardiomyovasculopathy (TGCV). We report a 59-year-old patient with NLSDM/TGCV presenting marked asymmetric skeletal myopathy and cardiomyovasculopathy. Skeletal muscle and endomyocardial biopsies showed cytoplasmic vacuoles containing neutral lipid. Gene analysis revealed a novel homozygous mutation (c.576delC) in PNPLA2. We reviewed 37 genetically-proven NLSDM/TGCV cases; median age was 30 years; distribution of myopathy was proximal (69%) and distal predominant (16%); asymmetric myopathy (right>left) was reported in 41% of the patients. Frequently-affected muscles were posterior compartment of leg (75%), shoulder girdle to upper arm (50%), and paraspinal (33%). Skeletal muscle biopsies showed lipid accumulation in 100% and rimmed vacuoles in 22%. Frequent comorbidities were cardiomyopathy (44%), hyperlipidemia (23%), diabetes mellitus (24%), and pancreatitis (14%). PNPLA2 mutations concentrated in Exon 4-7 without apparent genotype-phenotype correlations. To know the characteristic features is essential for the early diagnosis of NLSDM/TGCV.
Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai 980-8574, Japan.
Kimihiko
K
Kaneko
Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai 980-8574, Japan. Electronic address: dakuro@med.tohoku.ac.jp.
Hiroshi
H
Kuroda
Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai 980-8574, Japan.
Rumiko
R
Izumi
Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai 980-8574, Japan.
Maki
M
Tateyama
Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai 980-8574, Japan.
Masaaki
M
Kato
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai 980-8574, Japan.
Koichiro
K
Sugimura
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai 980-8574, Japan.
Yasuhiko
Y
Sakata
Department of Pathology, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan.
Yoshihiko
Y
Ikeda
Laboratory of Cardiovascular Disease, Novel, Non-invasive and Nutritional Therapeutics (CNT), Graduate School of Medicine, Osaka University, 6-2-3 Furuedai, Suita, Osaka 565-0874, Japan; Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Electronic address: khirano@cnt-osaka.com.
Ken-Ichi
K
Hirano
Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aobaku, Sendai 980-8574, Japan.
Masashi
M
Aoki
D009202:Cardiomyopathies / Q000235:genetics* / Q000473:pathology*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000235:genetics* / Q000473:pathology; D060005:Genotyping Techniques; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics* / Q000473:pathology*; D008297:Male; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000473:pathology; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology*; D009154:Mutation; D010641:Phenotype; D014057:Tomography, X-Ray Computed; D014280:Triglycerides / Q000378:metabolism; D000217:Acyltransferases
D008049:Lipase; D014280:Triglycerides; C494794:PNPLA2 protein, human; D000217:Acyltransferases
Adipose triglyceride lipase; Asymmetric myopathy; Neutral lipid storage disease with myopathy; Patatin-like phospholipase domain-containing 2; Triglyceride deposit cardiomyovasculopathy