Prevalence of GLA gene mutations and polymorphisms in patients with multiple sclerosis: A cross-sectional study.

Fabry Disease (FD) has been frequently proposed as possible underestimated differential diagnosis of Multiple Sclerosis (MS), but no study has been performed to test prevalence of GLA gene mutations in a population fulfilling diagnostic criteria of MS. Aim of this study is to determine the prevalence of GLA gene mutations in a large and representative population diagnosed with MS, simultaneously providing a critical revision of current literature reports of coexistence or misdiagnosis between these two conditions. In this mono-centric cross-sectional study, 927 patients fulfilling McDonald diagnostic criteria and encompassing all MS phenotypes were enrolled. Patients underwent evaluation of α-GalA activity and genotyping. Both genetic variants annotated as pathogenic and GVUS were considered. Estimated alleles frequencies were then compared to the ones reported in the gnomAD database. GLA gene variants were found in seven individuals. Five patients carried variants previously described having controversial impact on FD phenotype, and the analysis of exome database revealed that they are not rare among healthy individuals. One patient showed a new variant never described before, and another one carried a late-onset FD cardiac variant. The overall prevalence of GLA gene variants in MS patients is comparable to the one estimated in healthy population. This result is further supported by critical revision of current literature evidences of misdiagnosis between MS and FD, arguing in favour of independence between these disorders.

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Déclaration de conflit d'intérêts

Declaration of Competing Interest C.R. and G.P. received fees for speaking from Genzyme. S.C. received fees for speaking from Genzyme and Shire, and fees for speaking, travel grant and honoraria for serving as consultant to Amicus. E.R. received travel grant and honoraria for serving as consultant to Genzyme and Shire. R.L. received fees for speaking, travel grant and honoraria for serving as consultant from Teva, Merck, Genzyme, Novartis, Roche and Biogen. L.S., G.D. and M.I. received travel grant and honoraria as consultant to Genzyme and Shire. E.T. received fees for speaking from Scientific Press, Ars Educandi and Shire Italy. A.P. received travel grant and honoraria for serving as consultant to Genzyme, Shire and Amicus. The other Authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.