Emerging links between pediatric lysosomal storage diseases and adult parkinsonism

Daniel Ysselstein*, Joshua M. Shulman, Dimitri Krainc

*Corresponding author for this work

Research output: Contribution to journalReview article

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)614-624
Number of pages11
JournalMovement Disorders
Volume34
Issue number5
DOIs
StatePublished - May 1 2019

Fingerprint

Lysosomal Storage Diseases
Movement Disorders
Parkinsonian Disorders
Glucosylceramidase
Pediatrics
Gaucher Disease
Molecular Epidemiology
Neurologic Manifestations
Lysosomes
Biochemistry
Cell Biology
Homeostasis
Mutation
Genes
Therapeutics

Keywords

  • Parkinson's disease
  • genetics
  • lysosomal storage disease
  • movement disorders

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Ysselstein, Daniel ; Shulman, Joshua M. ; Krainc, Dimitri. / Emerging links between pediatric lysosomal storage diseases and adult parkinsonism. In: Movement Disorders. 2019 ; Vol. 34, No. 5. pp. 614-624.
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Emerging links between pediatric lysosomal storage diseases and adult parkinsonism. / Ysselstein, Daniel; Shulman, Joshua M.; Krainc, Dimitri.

In: Movement Disorders, Vol. 34, No. 5, 01.05.2019, p. 614-624.

Research output: Contribution to journalReview article

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AU - Shulman, Joshua M.

AU - Krainc, Dimitri

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N2 - 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.

AB - 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.

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