TY - JOUR T1 - Globotriaosylsphingosine (lyso-Gb<sub>3</sub>) and analogues in plasma and urine of patients with Fabry disease and correlations with long-term treatment and genotypes in a nationwide female Danish cohort JF - Journal of Medical Genetics JO - J Med Genet SP - 692 LP - 700 DO - 10.1136/jmedgenet-2020-107162 VL - 58 IS - 10 AU - Grigoris Effraimidis AU - Ulla Feldt-Rasmussen AU - Åse Krogh Rasmussen AU - Pamela Lavoie AU - Mona Abaoui AU - Michel Boutin AU - Christiane Auray-Blais Y1 - 2021/10/01 UR - http://jmg.bmj.com/content/58/10/692.abstract N2 - 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.All data relevant to the study are included in the article or uploaded as supplementary information. This research project involves prospective data (15 years) from a retrospective cohort. Patients were part of the nationwide Danish long-term clinical Fabry Disease cohort. ER -