Urinary globotriaosylceramide excretion correlates with the genotype in children and adults with Fabry disease
Section snippets
Materials and methods
This project was approved by the Research Ethics Board of the Faculty of Medicine and Health Sciences and the Sherbrooke Medical Centre.
LC–MS/MS analysis
Fig. 1 shows the total ion chromatogram (TIC) in MRM mode of a 5-year-old hemizygote with Fabry disease with the R301Q mutation excreting increased levels of total Gb3 and a normal control child. Complete analysis time is 2.6 min.
Comparison of two quantitative creatinine methodologies
Regarding the comparison between creatinine samples analyzed by the spectrophotometric technique and the multiplex LC–MS/MS method, the Friedmann test shows no difference between the two methods (χ2 = 0.19, p-value = 0.6629) for 47 urine filter paper samples.
Gb3
With total Gb3
Discussion
Previous efforts to analyze total Gb3 isoforms over the years were both time and labor intensive, necessitating sample dilution, extraction, ultrasonication, centrifugation and evaporation steps [29], [31], [43]. Creatinine is most frequently analyzed using the Jaffe method, but this is prone to interference by proteins, bilirubin and ketones [44]. On the other hand, specific constituents of blood have been analyzed simultaneously with creatinine [45], [46]. We have previously developed a
Acknowledgments
The authors thank the nurse-coordinators, geneticists and genetic counsellors at each collaborating centre: Carolina Azcona, (Toronto), Kaye Lemoine (Halifax), Carole Fortier (Montreal), Nicole Labbé (Quebec), and Dr. Karelle Benistan (Paris) and Dr. John James Mitchell (Montreal) for their collaboration in providing urine samples from Fabry patients. We acknowledge the assistance of Claude Alie and Dr. René Gagnon for their keen expertise. We are particularly grateful to the patients with
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