Persistently elevated CK and lysosomal storage myopathy associated with mucolipin 1 defects

Neuromuscul Disord. 2021 Mar;31(3):212-217. doi: 10.1016/j.nmd.2020.12.009. Epub 2021 Jan 6.


Mucolipidosis type IV is a rare autosomal recessive lysosomal storage disorder caused by bi-allelic pathogenic variants in the gene MCOLN1. This encodes for mucolipin-1 (ML1), an endo-lysosomal transmembrane Ca++ channel involved in vesicular trafficking. Although experimental models suggest that defects in mucolipin-1 can cause muscular dystrophy, putatively due to defective lysosomal-mediated sarcolemma repair, the role of mucolipin-1 in human muscle is still poorly deciphered. Elevation of creatine kinase (CK) had been reported in a few cases in the past but comprehensive descriptions of muscle pathology are lacking. Here we report a 7-year-old boy who underwent muscle biopsy due to persistently elevated CK levels (780-15,000 UI/L). Muscle pathology revealed features of a lysosomal storage myopathy with mild regenerative changes. Next generation sequencing confirmed homozygous nonsense variants in MCOLN1. This is a comprehensive pathological description of ML1-related myopathy, supporting the role of mucolipin-1 in muscle homoeostasis.

Keywords: Lysosome; Mucolipidosis IV; Mucolipin-1; Myopathy; Sarcolemma repair.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biopsy
  • Child
  • Creatine Kinase / metabolism*
  • Humans
  • Lysosomes
  • Male
  • Mucolipidoses / diagnosis*
  • Sarcolemma
  • Transient Receptor Potential Channels


  • MCOLN1 protein, human
  • Transient Receptor Potential Channels
  • Creatine Kinase