A somatic cell defect is associated with the onset of neurological symptoms in a lysosomal storage disease

Mol Genet Metab. Sep-Oct 2013;110(1-2):188-90. doi: 10.1016/j.ymgme.2013.06.010. Epub 2013 Jun 21.


Mutations in individuals with the lysosomal storage disorder Niemann-Pick disease, type C1 (NPC1) are heterogeneous, not localized to specific protein domains, and not correlated to time of onset or disease severity. We demonstrate direct correlation of the time of neurological symptom onset with the severity of lysosomal defects in NPC1 patient-derived fibroblasts. This is a novel assay for NPC1 individuals that may be predictive of NPC1 disease progression and broadly applicable to other lysosomal disorders.

Keywords: Lysosomal storage disorders; NPC1; Neurodegenerative disorders; Niemann–Pick disease, type C1.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Biological Transport / genetics
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Disease Progression
  • Female
  • Fibroblasts
  • Humans
  • Infant
  • Infant, Newborn
  • Lysosomal Storage Diseases / genetics*
  • Lysosomal Storage Diseases / metabolism
  • Lysosomal Storage Diseases / pathology
  • Lysosomes / genetics
  • Lysosomes / metabolism*
  • Lysosomes / pathology
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism
  • Mutation
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / pathology
  • Niemann-Pick Disease, Type C / genetics*
  • Niemann-Pick Disease, Type C / metabolism
  • Niemann-Pick Disease, Type C / pathology
  • Protein Structure, Tertiary


  • Membrane Glycoproteins