Background: Fabry disease is an inherited metabolic disorder with various symptoms. Neurological manifestations are small fiber neuropathy, cerebral white matter lesions (WML), megadolicho basilar artery, and stroke. The relevance of the D313Y variant in the galactosidase alpha gene is controversially discussed.
Objectives: We aimed at elucidating the implications of this differential diagnosis of multiple sclerosis (MS), focussing on the analysis of WML over time and correlations with other markers.
Methods: We reviewed retrospectively the clinical, laboratory, and magnetic resonance imaging data of 21 carriers of the D313Y variant at a single German outpatient clinic for MS between 2004 and 2021.
Results: In our cohort (15 females, 6 males), mean age at diagnosis was 44.1 ± 16.3 years, and mean follow-up duration was 3.1 ± 3.9 years. WML were rated on both, the Fazekas scale and the age-related white matter changes rating scale, and were of variable interindividual extent. Follow-up imaging showed virtually no progress. WML did not correlate with the severity of clinical findings or lysoGb3 levels. Symptomatic carriers of the variant are characterized by an almost complete lack of internal organ manifestations and laboratory findings, usually associated with Fabry disease.
Conclusion: WML in carriers of the D313Y variant do not seem to be suitable for assessing or predicting the (para-) clinical status. Concerning MS patients, the variant and its clinical signs can be a differential diagnosis, but also a co-factor. Imaging and cerebrospinal fluid findings facilitate the distinction between both entities.
Keywords: D313Y variant; Enzyme replacement therapy; Fabry disease; LysoGb3; Multiple sclerosis; White matter lesions.
© 2022. Fondazione Società Italiana di Neurologia.