Abstract
Objective
To describe demographic, genetic, and clinical characteristics of patients with neuronopathic Gaucher disease (NGD).
Methods
All patients enrolled in the Neurological Outcomes Subregistry of the International Collaborative Gaucher Group (ICGG) Gaucher Registry as of June 2007 were identified.
Results
The study cohort comprised 131 patients from 17 countries who were enrolled in the Neurological Outcomes Subregistry. The onset of neurological manifestations had occurred before 2 years of age in 47% (61 out of 131 patients), 2 years of age or older in 41% (54 out of 131), and could not be ascertained in the remaining 12% (16 out of 131). The most common manifestations were inability to look to the extreme up or down (45%, 55 out of 123), abnormally slow object tracking (43%, 53 out of 123), convergent squint (36%, 44 out of 121), and ataxia (15 to 20%, 18–27 out of 117). Seizures were reported in 19 out of 122 patients (16%), and myoclonic seizures were reported in 3 out of 121 patients (2%). The most common genotypes were L444P/L444P (76 out of 108, 70%), L444P/D409H (9 out of 108, 8%), D409H/D409H (8 out of 108, 7%), and L444P/rare allele (6 out of 108, 6%); full sequencing was not performed in all patients.
Conclusions
Neurological manifestations of GD often begin to appear before the age of 2 years. The most common neurological signs and manifestations are brainstem abnormalities and fine motor dysfunction. The most common genotype is L444P/L444P.
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Abbreviations
- GD:
-
Gaucher disease
- ICGG:
-
International Collaborative Gaucher Group
- NGD:
-
neuronopathic Gaucher disease
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Acknowledgements
We would like to thank the patients with neuronopathic Gaucher disease and their physicians and health care personnel who submit data to the Neurological Outcomes Subregistry, the Gaucher Registry support team at Genzyme Corporation, Andrea Gwosdow, Ph.D., for assistance in preparing the manuscript, Robert Brown (Genzyme Corporation) for graphic design of the figure, Michael Yeh, M.D. (Genzyme Corporation), for critical review of the manuscript and Pramod Mistry, M.D., Ph.D., for providing GBA1 gene sequencing for the Egyptian type 3 patients.
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Communicated by: Ed Wraith
Competing interests: J. Alexander Cole was employed by Genzyme Corporation when the work was conducted. A. Tylki-Szymańska receives speaking fees from Genzyme Corporation. A. Vellodi receives research grants and speaking fees from Genzyme Corporation. E. Kolodny receives a research grant from Genzyme Corporation. A. El-Beshlawy has no conflict of interest. The article was prepared by a professional medical writer (A. Gwosdow) who was supported by Genzyme Corporation.
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Tylki-Szymańska, A., Vellodi, A., El-Beshlawy, A. et al. Neuronopathic Gaucher disease: demographic and clinical features of 131 patients enrolled in the International Collaborative Gaucher Group Neurological Outcomes Subregistry. J Inherit Metab Dis 33, 339–346 (2010). https://doi.org/10.1007/s10545-009-9009-6
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DOI: https://doi.org/10.1007/s10545-009-9009-6