Clinicopathological-genetic features of neutral lipid storage disease with myopathy from a Chinese neuromuscular center

Orphanet J Rare Dis. 2025 Jul 1;20(1):322. doi: 10.1186/s13023-025-03861-7.

Abstract

Background: Neutral lipid storage disease with myopathy (NLSDM) is a rare genetic myopathy caused by mutations in the patatin-like phospholipase domain-containing protein (PNPLA2) gene. To date, the number of reported cases remains limited and the correlation between disease phenotypes and genotypes remains unclear.

Results: Our study presents eight NLSDM patients from a Chinese neuromuscular center, identifying two PNPLA2 novel mutations through next-generation sequencing. Demographic and clinical data, as well as information from muscle electrophysiological, imaging, pathological, and genetic analyses, were collected. Several patients in the cohort were found to have right upper extremity weakness as the initial clinical manifestation. Notably, the first patient with facial muscle involvement was reported in this series. Muscle histopathology revealed a characteristic accumulation of lipid droplets predominantly in type 1 muscle fibers, featuring type 1 fiber atrophy concurrent with type 2 fiber hypertrophy, which was systematically described first in a summary manner.

Conclusions: This study prompted us to summarize abnormal clinicopathological features and explore the relationship between gene mutations and disease phenotypes in NLSDM.

Keywords: PNPLA2; Lipid storage diseases; Myopathy; NLSDM; Neuromuscular disorder.

MeSH terms

  • Acyltransferases
  • Adolescent
  • Adult
  • Child
  • East Asian People
  • Female
  • Humans
  • Lipase / genetics
  • Lipid Metabolism, Inborn Errors* / genetics
  • Lipid Metabolism, Inborn Errors* / pathology
  • Male
  • Middle Aged
  • Muscular Diseases* / genetics
  • Muscular Diseases* / pathology
  • Mutation / genetics
  • Young Adult

Substances

  • Lipase
  • PNPLA2 protein, human
  • Acyltransferases

Supplementary concepts

  • Chinese people
  • Neutral Lipid Storage Disease with Myopathy