HyperCKemia: An early sign of childhood-onset neutral lipid storage disease with myopathy

Neuromuscul Disord. 2023 Sep;33(9):81-89. doi: 10.1016/j.nmd.2023.07.007. Epub 2023 Jul 30.


Neutral lipid-storage disease with myopathy (NLSDM) is an autosomal recessive neuromuscular disorder caused by mutations in PNPLA2, and the average age at onset is 30 years. To date, only eight patients with childhood-onset NLSDM have been reported in detail. We investigated 3 unreported patients with NLSDM detected in childhood and reviewed 8 childhood-onset and 82 adult-onset patients with NLSDM documented in the literature. In the childhood-onset cohort, NLSDM presented initially as asymptomatic or paucisymptomatic hyperCKemia in 6/11 patients, and follow-up data showed onset of muscle weakness in 6/11 childhood-onset patients. In the adult-onset cohort, 95.1% (78/82) of patients showed muscle weakness. Cardiac involvement developed in 6/11 childhood-onset patients. Hepatomegaly was observed in 3/11 childhood-onset patients. Serum creatine kinase levels were elevated greater than five-fold of the upper limit of normal (ULN) in most childhood-onset patients and were elevated to less than ten-fold of the ULN in most adult-onset patients. Peripheral blood smears and muscle biopsies showed cytoplasmic lipid droplets in leukocytes and myocytes. NLSDM can present in children with asymptomatic or paucisymptomatic hyperCKemia before the onset of muscle weakness. The presence of lipid droplets in leucocytes (Jordans' anomaly) aids in diagnosing and confirming the pathogenicity of PNPLA2 variants of uncertain significance. There were no clear genotype-phenotype correlations in patients with NLSDM.

Keywords: Childhood-onset; Jordans' anomaly; Neutral lipid storage disorders with myopathy; PNPLA2 gene; hyperCKemia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Child
  • Humans
  • Lipid Metabolism, Inborn Errors* / diagnosis
  • Lipid Metabolism, Inborn Errors* / genetics
  • Muscle Weakness
  • Muscular Diseases* / diagnosis
  • Muscular Diseases* / genetics

Supplementary concepts

  • Neutral Lipid Storage Disease with Myopathy
  • Chanarin-Dorfman Syndrome