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The risk of Parkinson’s disease in type 1 Gaucher disease

  • Original Article
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Journal of Inherited Metabolic Disease

Abstract

In Gaucher disease, defective lysosomal glucocerebrosidase due to mutations in the GBA1 gene results in lysosomal accumulation of glucocerebroside in mononuclear phagocytes and a multisystemic phenotype. Observations of occurrence of Parkinson’s disease in some patients with non-neuronopathic type 1 Gaucher disease (GD1) and their first degree relatives has led to the identification of GBA1 heterozygous mutations as a genetic risk factor for idiopathic Parkinson’s disease (PD). However, the magnitude of risk of PD in patients with known GD1 has not been determined, and it is not known whether GD1/PD represents a specific sub-phenotype of GD1 with distinctive genotype/phenotype characteristics. We estimated the risk of PD in a cohort of 444 consecutively evaluated patients with GD1 compared to that in the general population. Eleven patients developed parkinsonian syndrome during a 12-year follow-up period. The adjusted life-time risk ratio of PD in GD1 compared to that in the general population was 21.4 [95% confidence interval (95% CI) 10.7–38.3], with a higher risk in men compared to women. In our cohort, GD1/Parkinson’s disease phenotype (GD1/PD) was characterized by higher GD1 severity score, due to higher incidence of avascular osteonecrosis. The clinical spectrum of PD varied from mild to potentially life-threatening disease. All but one patient with GD1/PD phenotype had at least one N370S GBA1 allele. In conclusion, compared to the general population, patients with GD1 have an almost 20-fold increased life-time risk of developing PD.

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Acknowledgements

Preliminary data in this study were presented by P.K.M. at the National Institutes of Health (NIH) Workshop on Parkinson’s disease and Gaucher disease in March 2007. G.B. was supported by the National Institutes of Health (NIH) post-doctoral training program for investigative gastroenterology (grant. no. T32DK007356). P.K.M. was supported by the NIH mid-career clinical investigator award (grant no.  K24DK066306). We thank the National Gaucher Foundation for their support and the patients who participated in our studies.

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Authors and Affiliations

  1. Department of Pediatrics and Internal Medicine, Yale University School of Medicine, 333 Cedar Street, P.O. Box 208064, New Haven, CT, 06520-8064, USA

    Gilberto Bultron, Katherine Kacena, Daniel Pearson, Ruhua Yang & Pramod K. Mistry

  2. Arizona Hematology Oncology, Tucson, AZ, USA

    Michael Boxer

  3. Program for Neurogenetics, Department of Neurology, New York University School of Medicine, New York, NY, USA

    Swati Sathe & Gregory Pastores

Authors
  1. Gilberto Bultron
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  2. Katherine Kacena
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  3. Daniel Pearson
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  4. Michael Boxer
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  5. Ruhua Yang
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  6. Swati Sathe
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  7. Gregory Pastores
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  8. Pramod K. Mistry
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Corresponding author

Correspondence to Pramod K. Mistry.

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Communicated by: Frits Wijburg

Competing interest: None declared.

Gilberto Bultron and Katherine Kacena contributed equally to the manuscript

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Bultron, G., Kacena, K., Pearson, D. et al. The risk of Parkinson’s disease in type 1 Gaucher disease. J Inherit Metab Dis 33, 167–173 (2010). https://doi.org/10.1007/s10545-010-9055-0

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  • DOI: https://doi.org/10.1007/s10545-010-9055-0

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