Journal of Inherited Metabolic Disease

, Volume 36, Issue 3, pp 575–580 | Cite as

Greater risk of parkinsonism associated with non-N370S GBA1 mutations

  • M. J. Barrett
  • P. Giraldo
  • J. L. Capablo
  • P. Alfonso
  • P. Irun
  • B. Garcia-Rodriguez
  • M. Pocovi
  • G. M. Pastores
Original Article


Mutations in β-glucosidase (GBA1) are the most common genetic risk factor for Parkinson disease (PD). There is evidence to suggest that PD risk is greater (1) in GBA1 heterozygotes with non-N370S GBA1 mutations compared to N370S mutations and (2) in GD type 1 (GD1) patients compared to GBA1 heterozygotes. This study aimed to determine the comparative risk of parkinsonism in individuals who are affected or carriers of Gaucher disease (GD) and to ascertain the influence of different GBA1 mutations on risk/clinical expression. We conducted a secondary analysis of cross-sectional data assessing the prevalence of parkinsonism in a population of GD1 patients and their heterozygote and non-carrier family members. Two logistic regression models, both employing a family-specific random effect, were used to assess (1) the association between GBA1 mutation (N370S or non-N370S) and parkinsonism among GBA1 heterozygotes and (2) the association between GBA1 genotype and parkinsonism. Parkinsonism was present in 8.6 % of GD1 (7/81), 8.7 % of GBA1 heterozygotes (18/207), and 2.2 % of non-carriers (1/45). For those greater than 60 years old, parkinsonism was present in 38.5 % (5/13) of GD1 (5/13), 15.3 % of GBA1 heterozygotes (13/85), and 7.1 % of non-carriers (1/14). Among GBA1 heterozygotes, non-N370S mutations were associated with a significantly increased risk of parkinsonism compared to N370S (OR = 22.5; p = 0.035; 95%CI: 1.24, 411). In this population, each additional GBA1 mutation was associated with a non-significant two-fold increased risk of parkinsonism. GBA1 heterozygotes with non-N370S mutations associated with Gaucher disease have an increased risk of parkinsonism compared to those with N370S mutations.


Parkinson Disease Gauche Disease Parkinson Disease Patient Gauche Disease Patient GBA1 Mutation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors thank all the members of the Spanish Gaucher Disease Group (SGDG) who provided data. The complete list of physicians of the SGDG who have contributed is available at the website, The authors are also extremely grateful to the patients and their families whose participation made this work possible. This study was partially supported by the grants FIS PS09/2556, CIBERER, FEETEG and Fundación Ramón Areces 2010. MJB is supported by the Empire State Clinical Research Training Program and the Marcled Foundation. MJB is also supported in part by the CTSA Grant UL1RR025750, a component of the NIH, and roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official vies of the NCRR or NIH. The authors would also like to thank Yungtai Lo, Ph.D. of Albert Einstein College of Medicine for statistical assistance.

Details of funding

The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsors. Dr. Barrett is supported by the Empire State Clinical Research Training Program and the Marcled Foundation. He is also supported in part by the CTSA Grant UL1RR025750, a component of the NIH, and roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NCRR or NIH. Dr. Giraldo, Dr. Capablo, Dr. Alfonso, Dr. Irun, Dr. Garcia-Rodriguez, and Dr. Pocovi are members of the Spanish Study Group on Gaucher Disease, a group supported by the Spanish Gaucher Disease Foundation (FEETEG). Dr. Giraldo, Dr. Alfonso, Dr. Irun, and Dr. Pocovi are researchers at the Aragonés Institute of Public Health (I + CS). Dr. Giraldo, Dr. Capablo, Dr. Alfonso, Dr. Irun, and Dr. Pocovi are members of the Centro de Investigación Biomédica En Red de Enfermedades Raras (CIBERER), ISCIII, Zaragoza, Spain.

Conflict of interest


Supplementary material

10545_2012_9527_MOESM1_ESM.doc (332 kb)
ESM 1 (DOC 332 kb)


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Copyright information

© SSIEM and Springer 2012

Authors and Affiliations

  • M. J. Barrett
    • 1
  • P. Giraldo
    • 2
    • 3
    • 4
  • J. L. Capablo
    • 5
  • P. Alfonso
    • 2
    • 3
    • 4
  • P. Irun
    • 2
    • 3
  • B. Garcia-Rodriguez
    • 4
  • M. Pocovi
    • 3
    • 6
  • G. M. Pastores
    • 7
  1. 1.Department of NeurologyBeth Israel Medical CenterNew YorkUSA
  2. 2.Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER)ZaragozaSpain
  3. 3.Instituto de Investigación Sanitaria de Aragón (IIS)ZaragozaSpain
  4. 4.Translational Research UnitMiguel Servet University HospitalZaragozaSpain
  5. 5.Neurology DepartmentMiguel Servet University HospitalZaragozaSpain
  6. 6.Departamento de Bioquímica y Biología Molecular y CelularUniversidad de ZaragozaZaragozaSpain
  7. 7.Department of Neurology, Neurogenetics UnitNYU Langone Medical CenterNew YorkUSA

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