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

J Inherit Metab Dis. 2013 Sep;36(5):881-5. doi: 10.1007/s10545-012-9547-1. Epub 2012 Oct 30.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Child
  • Child, Preschool
  • Fabry Disease / blood
  • Fabry Disease / genetics*
  • Fabry Disease / metabolism*
  • Female
  • Glycolipids / blood
  • Glycolipids / genetics*
  • Glycolipids / metabolism*
  • Heterozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Mutation*
  • Phenotype
  • Pilot Projects
  • Sphingolipids / blood
  • Sphingolipids / genetics*
  • Sphingolipids / metabolism*
  • Young Adult


  • Biomarkers
  • Glycolipids
  • Sphingolipids
  • globotriaosyl lysosphingolipid