Lyso-globotriaosylsphingosine (lyso-Gb(3)) levels in neonates and adults with the Fabry disease later-onset GLA IVS4+919G > A mutation

Lyso-globotriaosylsphingosine (lyso-Gb(3)) is a useful biomarker in the diagnosis and monitoring of treatment for Fabry disease. However, it is unclear whether lyso-Gb(3) is elevated in patients with later-onset Fabry disease. Thus, we measured lyso-Gb(3) 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-Gb(3) 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-Gb(3) levels were elevated and were higher than in age-matched controls. The elevation of lyso-Gb(3) 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-Gb(3) levels is useful in the diagnosis of Fabry disease, including the later-onset phenotype. The DBS lyso-Gb(3) level was not elevated in IVS4+919G > A heterozygotes, and is not useful for their diagnosis. Since lyso-Gb(3) levels are elevated from birth in Fabry disease males, "an elevated lyso-Gb(3) level" may be of little values for deciding when to begin enzyme replacement therapy