Study of LPIN1, LPIN2 and LPIN3 in rhabdomyolysis and exercise-induced myalgia

J Inherit Metab Dis. 2012 Nov;35(6):1119-28. doi: 10.1007/s10545-012-9461-6. Epub 2012 Apr 6.


Background: Recessive LPIN1 mutations were identified as a cause of severe rhabdomyolysis in pediatric patients. The human lipin family includes two other closely related members, lipin-2 and 3, which share strong homology and similar activity. The study aimed to determine the involvement of the LPIN family genes in a cohort of pediatric and adult patients (n = 171) presenting with muscular symptoms, ranging from severe (CK >10 000 UI/L) or moderate (CK <10 000 UI/L) rhabdomyolysis (n = 141) to exercise-induced myalgia (n = 30), and to report the clinical findings in patients harboring mutations.

Methods: Coding regions of LPIN1, LPIN2 and LPIN3 genes were sequenced using genomic or complementary DNAs.

Results: Eighteen patients harbored two LPIN1 mutations, including a frequent intragenic deletion. All presented with severe episodes of rhabdomyolysis, starting before age 6 years except two (8 and 42 years). Few patients also suffered from permanent muscle symptoms, including the eldest ones (≥ 40 years). Around 3/4 of muscle biopsies showed accumulation of lipid droplets. At least 40% of heterozygous relatives presented muscular myalgia. Nine heterozygous SNPs in LPIN family genes were identified in milder phenotypes (mild rhabdomyolysis or myalgia). These variants were non-functional in yeast complementation assay based on respiratory activity, except the LPIN3-P24L variant.

Conclusion: LPIN1-related myolysis constitutes a major cause of early-onset rhabdomyolysis and occasionally in adults. Heterozygous LPIN1 mutations may cause mild muscular symptoms. No major defects of LPIN2 or LPIN3 genes were associated with muscular manifestations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cohort Studies
  • DNA, Complementary / genetics
  • Exercise
  • Female
  • Genes, Recessive
  • Genetic Complementation Test
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscular Diseases / genetics*
  • Muscular Diseases / pathology
  • Mutation*
  • Nuclear Proteins / genetics*
  • Phosphatidate Phosphatase / genetics*
  • Polymorphism, Single Nucleotide
  • Retrospective Studies
  • Rhabdomyolysis / genetics*
  • Rhabdomyolysis / pathology
  • Young Adult


  • DNA, Complementary
  • LPIN2 protein, human
  • Nuclear Proteins
  • LPIN1 protein, human
  • Phosphatidate Phosphatase