Introduction Recent studies showed the usefulness of globotriaosylsphingosine (lyso-Gb₃) and related analogues, deacylated forms of globotriaosylceramide (Gb₃), for high-risk screening, treatment monitoring and follow-up for patients with Fabry disease.

Methods We evaluated Gb₃, lyso-Gb₃ and analogues using tandem mass spectrometry in 57 women with Fabry disease followed during a period of 15.4 years. Twenty-one women were never treated and 36 received treatment (agalsidase-beta, n=30; agalsidase-alfa, n=5; or migalastat, n=1). Lyso-Gb₃ and analogues at m/z (−28), (−2), (+16), (+34) and (+50) were analysed in plasma and urine. Total Gb₃ and lyso-Gb₃ analogues at m/z (−12) and (+14) were evaluated in urine while the analogue at m/z (+18) was evaluated in plasma.

Results A strong correlation between plasma and urine lyso-Gb₃ and analogue levels was revealed. Plasma and urine lyso-Gb₃ and analogue levels were not statistically different between patients carrying missense (n=49), nonsense (n=6) or deletion mutations (n=2). Never treated patients had lower plasma lyso-Gb₃ and analogues at m/z (−28), (−2), (+16), (+34) and the seven urinary lyso-Gb₃ analogues compared with pretreatment levels of the treated patients. A significant reduction of plasma lyso-Gb₃ and five analogues, as well as urine Gb₃ and six lyso-Gb₃ analogues, but not lyso-Gb₃ and lyso-Gb₃ at m/z (+50), was observed post-treatment with agalsidase-beta. The same tendency was observed with agalsidase-alfa.

Conclusion Women with Fabry disease who started treatment based on clinical manifestations had higher lyso-Gb₃ and analogue biomarker levels than never treated women. This indicates that a biomarker cut-off could potentially be a decision tool for treatment initiation in women with Fabry disease.