Late onset of neutral lipid storage disease due to novel PNPLA2 mutations causing total loss of lipase activity in a patient with myopathy and slight cardiac involvement

Sara Missaglia, Lorenzo Maggi, Marina Mora, Sara Gibertini, Flavia Blasevich, Piergiuseppe Agostoni, Laura Moro, Denise Cassandrini, Filippo Maria Santorelli, Simonetta Gerevini, Daniela Tavian

Research output: Contribution to journalArticlepeer-review

Abstract

Neutral lipid storage disease with myopathy (NLSDM) presents with skeletal muscle myopathy and severe dilated cardiomyopathy in nearly 40% of cases. NLSDM is caused by mutations in the PNPLA2 gene, which encodes the adipose triglyceride lipase (ATGL). Here we report clinical and genetic findings of a patient carrying two novel PNPLA2 mutations (c.696+4A>G and c.553_565delGTCCCCCTTCTCG). She presented at age 39 with right upper limb abduction weakness slowly progressing over the years with asymmetric involvement of proximal upper and lower limb muscles. Cardiological evaluation through ECG and heart echo scan was normal until the age 53, when mild left ventricular diastolic dysfunction was detected. Molecular analysis revealed that only one type of PNPLA2 transcript, with exon 5 skipping, was expressed in patient cells. Such aberrant mRNA causes the production of a shorter ATGL protein, lacking part of the catalytic domain. This is an intriguing case, displaying severe PNPLA2 mutations with clinical presentation characterized by slight cardiac impairment and full expression of severe asymmetric myopathy.

Original languageEnglish
Pages (from-to)481-486
Number of pages6
JournalNeuromuscular Disorders
Volume27
Issue number5
DOIs
Publication statusPublished - May 2017

Keywords

  • Cardiomyopathies
  • Female
  • Humans
  • Lipase
  • Lipid Metabolism, Inborn Errors
  • Middle Aged
  • Muscles
  • Muscular Diseases
  • Mutation
  • Case Reports
  • Journal Article

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