A novel mutation in PNPLA2 causes neutral lipid storage disease with myopathy and triglyceride deposit cardiomyovasculopathy: a case report and literature review

Neuromuscul Disord. 2014 Jul;24(7):634-41. doi: 10.1016/j.nmd.2014.04.001. Epub 2014 Apr 21.


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.

Keywords: Adipose triglyceride lipase; Asymmetric myopathy; Neutral lipid storage disease with myopathy; Patatin-like phospholipase domain-containing 2; Triglyceride deposit cardiomyovasculopathy.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Cardiomyopathies / genetics*
  • Cardiomyopathies / pathology*
  • Coronary Angiography
  • Coronary Artery Disease / genetics*
  • Coronary Artery Disease / pathology
  • Genotyping Techniques
  • Humans
  • Lipase / genetics*
  • Lipid Metabolism, Inborn Errors / genetics*
  • Lipid Metabolism, Inborn Errors / pathology*
  • Male
  • Microscopy, Electron, Transmission
  • Middle Aged
  • Muscle, Skeletal / pathology
  • Muscular Diseases / genetics*
  • Muscular Diseases / pathology*
  • Mutation*
  • Phenotype
  • Tomography, X-Ray Computed
  • Triglycerides / metabolism


  • Triglycerides
  • Lipase
  • PNPLA2 protein, human

Supplementary concepts

  • Neutral Lipid Storage Disease with Myopathy