Elevated Lyso-Gb3 Suggests the R118C GLA Mutation Is a Pathological Fabry Variant

Background: Fabry disease (FD), an X-linked lysosomal storage disease, results from an α-galactosidase A deficiency and altered sphingolipid metabolism. An accumulation of globotriaosylsphingosine (lyso-Gb3) likely triggers the pathological cascade leading to disease phenotype. The pathogenic significance of several Fabry mutations including the R118C α-galactosidase (GLA) gene variant has been disputed. We describe three members of the same family with the R118C variant, each having documented clinical signs of FD, low residual enzyme levels, and an elevated lyso-Gb3 in one heterozygote.