Emerging links between pediatric lysosomal storage diseases and adult parkinsonism

Mov Disord. 2019 May;34(5):614-624. doi: 10.1002/mds.27631. Epub 2019 Feb 6.


Lysosomal storage disorders comprise a clinically heterogeneous group of autosomal-recessive or X-linked genetic syndromes caused by disruption of lysosomal biogenesis or function resulting in accumulation of nondegraded substrates. Although lysosomal storage disorders are diagnosed predominantly in children, many show variable expressivity with clinical presentations possible later in life. Given the important role of lysosomes in neuronal homeostasis, neurological manifestations, including movement disorders, can accompany many lysosomal storage disorders. Over the last decade, evidence from genetics, clinical epidemiology, cell biology, and biochemistry have converged to implicate links between lysosomal storage disorders and adult-onset movement disorders. The strongest evidence comes from mutations in Glucocerebrosidase, which cause Gaucher's disease and are among the most common and potent risk factors for PD. However, recently, many additional lysosomal storage disorder genes have been similarly implicated, including SMPD1, ATP13A2, GALC, and others. Examination of these links can offer insight into pathogenesis of PD and guide development of new therapeutic strategies. We systematically review the emerging genetic links between lysosomal storage disorders and PD. © 2019 International Parkinson and Movement Disorder Society.

Keywords: Parkinson's disease; genetics; lysosomal storage disease; movement disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adult
  • Child
  • Galactosylceramidase / genetics
  • Gaucher Disease / genetics
  • Glucosylceramidase / genetics
  • Humans
  • Leukodystrophy, Globoid Cell / genetics
  • Lysosomal Storage Diseases / genetics*
  • Mucopolysaccharidosis III / genetics
  • Mutation
  • Neuronal Ceroid-Lipofuscinoses / genetics
  • Niemann-Pick Diseases / genetics
  • Parkinson Disease / genetics
  • Parkinsonian Disorders / genetics*
  • Phenotype
  • Proton-Translocating ATPases / genetics
  • Sandhoff Disease / genetics
  • Sphingomyelin Phosphodiesterase / genetics


  • ATP13A2 protein, human
  • SMPD1 protein, human
  • Sphingomyelin Phosphodiesterase
  • Glucosylceramidase
  • Galactosylceramidase
  • Proton-Translocating ATPases

Supplementary concepts

  • Kufor-Rakeb syndrome