Plasma globotriaosylsphingosine as a biomarker of Fabry disease

Mol Genet Metab. 2010 Jul;100(3):257-61. doi: 10.1016/j.ymgme.2010.03.020. Epub 2010 Apr 1.


Fabry disease is an X-linked genetic disorder caused by a deficiency of alpha-galactosidase A (GLA) activity. As enzyme replacement therapy (ERT) involving recombinant GLAs has been introduced for this disease, a useful biomarker for diagnosis and monitoring of therapy has been strongly required. We measured globotriaosylsphingosine (lyso-Gb3) and globotriaosylceramide (Gb3) in plasma samples from ten hemizygous males (six classic and four variant cases) and eight heterozygous females with Fabry disease, and investigated the responses of plasma lyso-Gb3 and Gb3 in a male Fabry patient who had undergone ERT for 4years to determine whether plasma lyso-Gb3 and Gb3 could be biomarkers of Fabry disease. The results revealed that plasma lyso-Gb3 was apparently increased in male patients and was higher in cases of the classic form than those of the variant one. In Fabry females, plasma lyso-Gb3 was moderately increased in both symptomatic and asymptomatic cases, and there was a correlation between the increase in lyso-Gb3 and the decrease in GLA activity. As to plasma Gb3, the levels in the variant Fabry hemizygotes and Fabry heterozygotes could not be distinguished from those in the controls, although those in the classic Fabry hemizygotes were increased. The plasma lyso-Gb3 level in the Fabry patient who had received ERT was elevated at the baseline and fell more dramatically on ERT than that of Gb3. Plasma lyso-Gb3 could thus be a potential biomarker of Fabry disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / blood
  • Case-Control Studies
  • Fabry Disease / blood*
  • Fabry Disease / drug therapy
  • Fabry Disease / genetics
  • Female
  • Glycolipids / blood*
  • Heterozygote
  • Humans
  • Male
  • Middle Aged
  • Recombinant Proteins / therapeutic use
  • Sphingolipids / blood*
  • Trihexosylceramides / blood*
  • Young Adult
  • alpha-Galactosidase / blood
  • alpha-Galactosidase / genetics
  • alpha-Galactosidase / therapeutic use


  • Biomarkers
  • Glycolipids
  • Recombinant Proteins
  • Sphingolipids
  • Trihexosylceramides
  • globotriaosyl lysosphingolipid
  • globotriaosylceramide
  • alpha-Galactosidase