Journal of Inherited Metabolic Disease

, Volume 33, Issue 2, pp 167–173

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

  • Gilberto Bultron
  • Katherine Kacena
  • Daniel Pearson
  • Michael Boxer
  • Ruhua Yang
  • Swati Sathe
  • Gregory Pastores
  • Pramod K. Mistry
Original Article

DOI: 10.1007/s10545-010-9055-0

Cite this article as:
Bultron, G., Kacena, K., Pearson, D. et al. J Inherit Metab Dis (2010) 33: 167. doi:10.1007/s10545-010-9055-0

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.

Copyright information

© SSIEM and Springer 2010

Authors and Affiliations

  • Gilberto Bultron
    • 1
  • Katherine Kacena
    • 1
  • Daniel Pearson
    • 1
  • Michael Boxer
    • 2
  • Ruhua Yang
    • 1
  • Swati Sathe
    • 3
  • Gregory Pastores
    • 3
  • Pramod K. Mistry
    • 1
  1. 1.Department of Pediatrics and Internal MedicineYale University School of MedicineNew HavenUSA
  2. 2.Arizona Hematology OncologyTucsonUSA
  3. 3.Program for Neurogenetics, Department of NeurologyNew York University School of MedicineNew YorkUSA