Dorsal root ganglia volume is increased in patients with the Fabry-related GLA variant p.D313Y.
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.
['Godel|Tim|T|', 'Bäumer|Philipp|P|', 'Stumpfe|Katharina|K|', 'Muschol|Nicole|N|', 'Kronlage|Moritz|M|', 'Brunnée|Merle|M|', 'Kollmer|Jennifer|J|', 'Heiland|Sabine|S|', 'Bendszus|Martin|M|', 'Mautner|Victor-Felix|VF|']
D000328:Adult D000368:Aged D002199:Capillary Permeability D000795:Fabry Disease D005260:Female D005727:Ganglia, Spinal D006801:Humans D008279:Magnetic Resonance Imaging D008875:Middle Aged D009154:Mutation D010523:Peripheral Nervous System Diseases D011446:Prospective Studies D012584:Sciatic Nerve D055815:Young Adult D000519:alpha-Galactosidase
Dorsal root ganglia Magnetic resonance neurography Fabry disease Neuropathic pain Peripheral neuropathy