Is globotriaosylceramide a useful biomarker in Fabry disease?

Aim: The aim of this study was to determine whether globotriaosylceramide (Gb(3)) is a useful biomarker in Fabry disease. Methods: The levels of Gb3 were measured in plasma and urine by tandem mass spectrometry in untreated hemizygotes and heterozygotes with Fabry disease and in healthy controls, and the levels were monitored in patients on treatment with enzyme replacement therapy (ERT). Results: Hemizygotes with classic Fabry disease showed elevated levels of Gb(3) in both plasma and urine and could readily be distinguished from normal controls. Male patients with the N215S mutation had normal levels in their plasma but 50% had marginally elevated levels in their urine. Thirty-three percent of proven heterozygotes had elevated Gb(3) concentrations in plasma but 97% of those without the N215S mutation (36/37) had an elevated level in urine. The four heterozygotes with the N215S mutation had normal Gb(3) levels in urine. The level of Gb(3) in plasma initially fell following the start of ERT in all patients who had an elevated level before treatment. However, in a few patients the level subsequently rose. Similar results were found for the levels of Gb(3) in urine. Conclusion: Gb(3) is not an ideal marker of Fabry disease or the response to treatment in all patients. Plasma and urine levels of Gb(3) cannot be used as a marker of Fabry disease in patients with the N215S mutation and many heterozygotes do not have elevated Gb(3) levels in plasma. The urine concentration is more informative in heterozygotes and can be used as a measure of the response to therapy. The fall in Gb(3) levels in patients receiving ERT was not sustained in some patients, despite a clinical improvement. Additionally, Gb(3) cannot be used to monitor the response to treatment in patients who initially have normal plasma and urine concentrations of this glycolipid.