Symptomatic lipid storage in carriers for the PNPLA2 gene

Mirian C.H. Janssen, Baziel Van Engelen, Livia Kapusta, Martin Lammens, Martin Van Dijk, Judith Fischer, Marinette Van Der Graaf, Ron A. Wevers, Manuela Fahrleitner, Robert Zimmermann, Eva Morava*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Neutral lipid storage disease comprises a heterogeneous group of inherited disorders characterized by severe accumulation of cytoplasmic triglyceride droplets in several tissues and neutrophils. A novel type of autosomal recessive lipid myopathy due to PNPLA2 mutations was recently described with associated cardiac disease, myopathy and frequent infections, but without ichthyosis. Here we describe the clinical and biochemical characteristics of a long surviving patient and report on four carrier family members with diverse clinical involvement. Interestingly, heterozygous patients show neutral lipid storage in muscle and in the keratocytes of the skin, Jordans' bodies, mild myopathy and frequent infections. Biochemical analysis of fibroblasts obtained from patients revealed increased triglyceride storage and reduced lipid droplet-associated triglyceride hydrolase activity. Together, our data implicate that the wild-type allele cannot fully compensate for the mutated dysfunctional allele of PNPLA2 leading to triglyceride accumulation in muscle and mild myopathy in PNPLA2 mutation carriers. The presence of neutral lipid droplets in the skin in PNPLA2 mutation carriers strengthens the link between NLSD and other neutral lipid storage diseases with ichthyosis.

Original languageEnglish
Pages (from-to)807-815
Number of pages9
JournalEuropean Journal of Human Genetics
Issue number8
StatePublished - Aug 2013
Externally publishedYes


  • Deafness
  • Implantable cardioverter-defibrillator
  • Insulin resistance
  • Lipid myopathy
  • Neutral lipid storage
  • Symptomatic carriers


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