Clinical evaluation of sibling pairs with gaucher disease discordant for parkinsonism

Mov Disord. 2020 Feb;35(2):359-365. doi: 10.1002/mds.27916. Epub 2019 Nov 30.


Background: Although the association between mutations in GBA1 and parkinsonism is well established, most GBA1 mutation carriers never develop parkinsonism, implicating the contribution of other genetic, epigenetic, and/or environmental modifiers.

Objectives: To identify factors predisposing to or offering protection from parkinsonism among siblings with Gaucher's disease) discordant for Parkinson disease (PD).

Methods: This prospective, longitudinal study included nine sib pairs with Gaucher disease, but discordant for PD. Assessments included neurological, neuropsychological, olfactory, motor, nonmotor evaluations, and transcranial sonography. Validated mood and nonmotor questionnaires assessed fatigue, olfactory dysfunction, sleepiness, sleep disturbances, anxiety, and/or depression.

Results: There was no relationship between Gaucher treatments, genotype, or splenectomy and PD. Male sex predominance, younger age, and milder Gaucher disease symptoms were observed among the patients with PD. Substantia nigral echogenicity, olfactory dysfunction, serum triglycerides levels, and 9-hole peg scores, but not caffeine, alcohol, or tobacco use, environmental exposures, uric acid, or glucose levels, differed significantly between groups.

Conclusions: Longitudinal evaluation of discordant sib pairs may help identify PD risk factors. © 2019 International Parkinson and Movement Disorder Society.

Keywords: GBA1; Parkinson's disease; genetics; glucocerebrosidase; risk factors.

Publication types

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

MeSH terms

  • Adult
  • Female
  • Gaucher Disease / diagnosis
  • Gaucher Disease / genetics*
  • Glucosylceramidase / genetics*
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Mutation / genetics
  • Parkinsonian Disorders / diagnosis
  • Parkinsonian Disorders / genetics*
  • Risk Factors
  • Siblings


  • Glucosylceramidase