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Dorsal root ganglia volume is increased in patients with the Fabry-related GLA variant p.D313Y

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Abstract

Purpose

To examine dorsal root ganglia and proximal nerve segments in patients carrying the Fabry-related GLA-gene variant p.D313Y in comparison to patients with classical Fabry mutations and healthy controls by morphometric and functional magnetic resonance neurography.

Methods

This prospective multicenter study examines the lumbosacral dorsal root ganglia and sciatic nerve in 11 female p.D313Y patients by a standardized magnetic resonance neurography protocol at 3 T. Volumes of dorsal root ganglia L3 to S2, permeability of dorsal root ganglia L5 and S1, and spinal nerve L5 as well as cross-sectional area of the sciatic nerve were assessed and compared to 10 females carrying a classical Fabry mutation and 16 healthy female controls.

Results

Compared to healthy controls, dorsal root ganglia volumes of p.D313Y females were enlarged by 53% (L3), 48% (L4), 43% (L5), 57% (S1) (p < 0.001), and 55% (S2) (p < 0.05), but less pronounced compared to females carrying a classical Fabry mutation. Compared to healthy controls, p.D313Y patients showed no changes of dorsal root ganglia vascular permeability, while patients with a classical Fabry mutation showed a distinct decrease (p < 0.05). Sciatic nerve cross-sectional area was mildly increased by 6% in p.D313Y as well as in classical Fabry patients (p < 0.05).

Conclusions

Patients carrying the GLA-gene variant p.D313Y show distinctly enlarged dorsal root ganglia, while vascular permeability remains within normal limits. Overall, these alterations partially share characteristics commonly seen in patients with a mutation causing classical FD. This suggests that p.D313Y causes a potentially treatable condition resembling an early stage of Fabry disease.

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Acknowledgements

We thank all patients for their valuable cooperation in this study. T.G. is supported by a postdoctoral fellowship from the Medical Faculty of the University of Heidelberg and received a research grant from Amicus Therapeutics. N.M. received travel grants, research grants and speaker honoraria from Shire, Sanofi Genzyme, and Amicus. J.K. received a research grant and personal fees from Alnylam Pharmaceuticals, the Olympia Morata stipend grant from the Medical Faculty of the University of Heidelberg, and lecture honoraria and financial support for conference attendance from Pfizer. She also advises for Akcea Therapeutics. M.B. received grants from the German Research Council (SFB 1158). S.H. was supported by a grant from the German Research Council (SFB 1118). V.M. was supported by a grant from the Märta and Erik Karberg Foundation for Medical Research.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Neuroradiology, Neurological University Clinic, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany

    Tim Godel, Philipp Bäumer, Moritz Kronlage, Merle Brunnée, Jennifer Kollmer, Sabine Heiland & Martin Bendszus

  2. Center for Radiology Dia.log, Vinzenz-von-Paul Str. 8, 84503, Altötting, Germany

    Philipp Bäumer

  3. Department of Pediatrics, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany

    Katharina Stumpfe & Nicole Muschol

  4. Department of Neurology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246, Hamburg, Germany

    Victor-Felix Mautner

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  1. Tim Godel
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Correspondence to Tim Godel.

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Godel, T., Bäumer, P., Stumpfe, K. et al. Dorsal root ganglia volume is increased in patients with the Fabry-related GLA variant p.D313Y. J Neurol 266, 1332–1339 (2019). https://doi.org/10.1007/s00415-019-09262-8

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  • DOI: https://doi.org/10.1007/s00415-019-09262-8

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