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Research paper
Evolution of prodromal parkinsonian features in a cohort of GBA mutation-positive individuals: a 6-year longitudinal study
  1. Micol Avenali1,2,
  2. Marco Toffoli3,
  3. Stephen Mullin3,
  4. Alisdair McNeil3,
  5. Derralynn A Hughes4,
  6. A Mehta4,
  7. Fabio Blandini5,
  8. Anthony H V Schapira3
  1. 1Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy
  2. 2Neurorehabilitation Unit, IRCCS Mondino Foundation, Pavia, Italy
  3. 3Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK
  4. 4Lysosomal Storage Disorders Unit, Department of Haematology, Royal Free Hospital, UCL Medical School, London, UK
  5. 5Laboratory of Cellular and Molecular Neurobiology, IRCCS Mondino Foundation, Pavia, Italy
  1. Correspondence to Anthony H V Schapira, Clinical Neurosciences, UCL Institute of Neurology, London NW3 2PF, UK; a.schapira{at}


Objectives GBA1 mutations are a frequent risk factor for Parkinson disease (PD). The aim of this study is to evaluate clinical features in a group of GBA1 mutation–positive individuals over a 6-year follow-up.

Methods This is a longitudinal study on a cohort of GBA1-positive carriers. We enrolled 31 patients with Gaucher disease type 1 (GD), 29 GBA1 heterozygous carriers (Het GBA group) and 30 controls (HC) at baseline and followed them for 6 years. We assessed baseline motor and non-motor signs of PD in all subjects using clinical questionnaires and scales (reduced Unified Multiple System Atrophy Rating Scale (UMSARS), Montreal Cognitive assessment (MoCA), University of Pennsylvania Smell Identification Test (UPSIT), REM Sleep Behavior Disorder screening questionnaire (RBDsq), Movement Disorders Society Unified Parkinson’s Disease Rating Scale motor subscale (MDS-UPDRS III) and Beck Depression Inventory (BDI). We repeated these at the 6-year follow-up alongside venous blood sampling for measurement of glucocerebrosidase enzymatic activity (GCase). We explored whether the GCase activity level was altered in leucocytes of these subjects and how it was related to development of PD.

Results We observed a significant worsening in UMSARS, RBDsq, MDS-UPDRS III and BDI scores at the 6-year follow-up compared with baseline in both the GD and Het GBA groups. Intergroup comparisons showed that GD subjects had significantly worse scores in UPSIT, UMSARS, MoCA and MDS-UPDRS III than HC, while Het GBA displayed worse outcomes in UPSIT and MDS-UPDRS III compared with HC. In GBA1 mutation–positive individuals (Het GBA and GD), an UPSIT score of 23 at baseline was correlated with worse outcome at 6 years in UPSIT, MoCA, MDS-UPDRS III and BDI.

Conclusion In this 6-year-long longitudinal study, GBA1 mutation–positive subjects showed a worsening in motor and non-motor prodromal PD features.

  • parkinson’s disease
  • GBA
  • olfaction
  • gaucher disease
  • neurodegeneration

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  • MA and MT contributed equally.

  • Contributors MA and MT contributed equally to this work. Study concept and design: AHVS. Acquisition, analysis or interpretation of data: MA, MT, SM, AM. Drafting of the manuscript: MA, MT, AHVS. Critical revision of the manuscript for important intellectual content: FB, DAH, AM. Study supervision: AHVS.

  • Funding The study was funded through grants from the Medical Research Council (MR/M006646/1), the JNPD (Joint Program—Neurodegenerative Disease Research) (MR/N028651/1), Parkinson’s UK (G-1403) and was supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre.

  • Disclaimer The sponsors did not have any role in the study design; in the collection, analysis and interpretation of the data; in the writing of the report; and in the decision to submit the paper for publication.

  • Competing interests None declared.

  • Patient consent for publication Obtained.

  • Ethics approval The protocol was approved by the North-West London Research Ethics Committee (reference no. 10/H0720/21).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement All data relevant to the study are included in the article or uploaded as supplementary information.