Abstract
Gaucher’s disease (GD) is a hereditary lysosomal storage disease characterized by abnormal deposition of glucocerebroside due to the enzyme glucocerebrosidase deficiency, resulting in multi-organ pathology. GD type III has a progressive neurological involvement. We studied the vestibular and saccadic abnormalities in GD type III to determine if these parameters may be useful for assessing neurological involvement. We evaluated the vestibular and saccadic responses of two siblings with genetically identified GD type III on enzyme replacement therapy. Vestibular functions were assessed with the head impulse test (HIT), vestibular evoked myogenic potentials (VEMPs), and electrical vestibular stimulation (EVS). Saccadic functions were investigated with volitional horizontal and vertical saccades to ±20°. Three-dimensional head and eye movements were recorded with dual-search coils and VEMP with surface electrodes. HIT showed impaired individual semicircular canal function with halved angular vestibulo-ocular reflex (VOR) gains and absent horizontal refixation saccade. Ocular and cervical VEMPs to air-conducted clicks were absent in the older sibling, and only cervical VEMP was present in the younger sibling indicating otolithic dysfunction. EVS showed prolonged onset latency and attenuated tonic and phasic responses suggesting impaired neural conduction and vestibular function. Horizontal saccadic velocity was miniscule (<30°/s) and multiple back-to-back saccades with saccade-vergence interaction were utilized to minimize eye position error in the older sibling. Vertical saccades were slightly abnormal, but vergence and smooth pursuit were normal in both siblings. Our findings suggest that GD affected the vestibular nuclei in addition to the paramedian pontine reticular formation. These vestibular and saccadic abnormalities may be useful biomarkers to monitor neurological deterioration.
Competing interests: None declared
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Acknowledgments
This study was supported by National Health and Medical Research Council, Garnett Passe and Rodney Williams Memorial Foundation, The University of Sydney, Neurology Trustees Royal Prince Alfred Hospital.
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Communicated by: Ashok Vellodi
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Take-Home Message
Gaucher’s disease has distinctive vestibular and eye movement abnormalities, which could be used as biomarkers of neurological involvement.
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Conflict of Interest
Luke Chen declares that he has no conflict of interest.
Michael J Todd declares that he has no conflict of interest.
G Michael Halmagyi is an unpaid consultant of GN Otometrics and received funding for travel related to GN Otometrics.
Swee T Aw declares that she has no conflict of interest.
Informed Consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation: Sydney Local Health District, Approval No: X10-0085, University of Sydney, Database No. 13076, and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.
No identifying information about patients is included in the article.
Contributions of Individual Authors
Luke Chen tested the patients, analyzed their data, assisted in interpreting the data, preparing and revising the manuscript for intellectual content.
Michael J Todd designed and implemented the hardware and software for data collection and data analysis and assisted in revising the manuscript for intellectual content.
G Michael Halmagyi recruited the patients from Royal Prince Alfred Hospital, Australia, and assisted in revising the manuscript for intellectual content.
Swee T Aw designed the study, prepared and interpreted all the research data and figures. She was in charge of drafting, revising for intellectual content, and submitting the manuscript.
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Dr SweeT Aw serves as guarantor for the article, accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish.
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This study was funded by the National Health and Medical Research Council Australia, Garnett Passe and Rodney Williams Memorial Foundation, University of Sydney, and Royal Prince Alfred Hospital Neurology Trustees. The authors confirm independence from the sponsors; the content of the article has not been influenced by the sponsors.
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Chen, L., Halmagyi, G.M., Todd, M.J., Aw, S.T. (2013). Vestibular and Saccadic Abnormalities in Gaucher’s Disease. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports - Case and Research Reports, Volume 13. JIMD Reports, vol 13. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2013_264
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DOI: https://doi.org/10.1007/8904_2013_264
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