Lyso-globotriaosylsphingosine (lyso-Gb₃) levels in neonates and adults with the Fabry disease later-onset GLA IVS4+919G>A mutation

Lyso-globotriaosylsphingosine (lyso-Gb₃) is a useful biomarker in the diagnosis and monitoring of treatment for Fabry disease. However, it is unclear whether lyso-Gb₃ is elevated in patients with later-onset Fabry disease. Thus, we measured lyso-Gb₃ levels from dried blood spots (DBS) from male newborns with the Fabry disease later-onset phenotype, IVS4+919G>A mutation, and their family members. The lyso-Gb₃ levels were below the detection limit in normal control newborns and were slightly higher in adults. In males of all ages with the IVS4+919G>A mutation, lyso-Gb₃ levels were elevated and were higher than in age-matched controls. The elevation of lyso-Gb₃ levels in males with the IVS4+919G>A mutation was only slightly elevated compared with patients with the classical Fabry phenotype. The measurement of lyso-Gb₃ levels is useful in the diagnosis of Fabry disease, including the later-onset phenotype. The DBS lyso-Gb₃ level was not elevated in IVS4+919G>A heterozygotes, and is not useful for their diagnosis. Since lyso-Gb₃ levels are elevated from birth in Fabry disease males, “an elevated lyso-Gb₃ level” may be of little values for deciding when to begin enzyme replacement therapy.