Evaluation of the urinary globotriaosylceramide (Gb3) assay by tandem mass spectrometry
Molecular & cellular toxicology v.6 no.2 ,	2010년, pp.203 - 207
Song, Min-Jung (Department of Laboratory Medicine & Genetics, Sunkyunkwan University School of Medicine, Samsung Medical Center ) ; Ji, Ok-Ja ( Department of Laboratory Medicine & Genetics, Sunkyunkwan University School of Medicine, Samsung Medical Center ) ; Park, Hyung-Doo ( Department of Laboratory Medicine & Genetics, Sunkyunkwan University School of Medicine, Samsung Medical Center ) ; Jin, Dong-Kyu ( Department of Pediatrics, Sunkyunkwan University School of Medicine, Samsung Medical Center ) ; Lee, Soo-Youn ( Department of Laboratory Medicine & Genetics, Sunkyunkwan University School of Medicine, Samsung Medical Center)
Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from a deficiency of $\alpha$-galactosidase A, which leads to the progressive accumulation of one biomarker, globotriaosylceramide (Gb3), prominently elevated in the urine of affected patients. Using filter paper discs saturated with urine, we evaluated the analytical performance and clinical usefulness of the urinary Gb3 assay by tandem mass spectrometry (LC-MS/MS), with respect to linearity, precision, and reproducibility. We used healthy control urine samples to validate the reference interval of urinary Gb3. This method showed a good linearity ($R^2=0.9998$) in the range of $0.05-10\;{\mu}g/mL$. Within-run CVs were less than 5% and total CVs were within 10%. The mean recovery of Gb3 from the urine filter paper was 96.7% and the limit of quantification (S/N $\geq$ 5) was $0.05\;{\mu}g/mL$, which was sensitive enough for the diagnosis of FD. The mean concentration of Gb3 in urine samples from healthy Korean controls was $5.93{\pm}3.6\;{\mu}g/mmol$ Cr (range $0.9-16.43\;{\mu}g/mmol$ Cr). The urinary Gb3 assay by LC-MS/MS showed good analytical performance required for the diagnosis of FD in its linearity, precision, and accuracy. Therefore, this technique could be used for a rapid and reliable first line screening, monitoring and/or diagnosis of individuals at high risk for FD.
#Fabry disease #Globotriaosylceramide #Tandem mass spectrometry #Urine filter paper
Desnick, R. J., Wasserstein, M. P. & Banikazemi, M. Fabry disease (alpha-galactosidase A deficiency): renal involvement and enzyme replacement therapy. Contrib Nephrol 174-192(2001).
Nelson, B. C. et al. Globotriaosylceramide isoform profiles in human plasma by liquid chromatographytandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 805:127-134(2004).
Desnick, R. J. et al. Fabry disease, an under-recognized multisystemic disorder: expert recommendations for diagnosis, management, and enzyme replacement therapy. Ann Intern Med 138:338-346 (2003).
Thurberg, B. L. et al. Globotriaosylceramide accumulation in the Fabry kidney is cleared from multiple cell types after enzyme replacement therapy. Kidney Int 62:1933-1946 (2002).
Auray-Blais, C., Cyr, D., Mills, K., Giguere, R. & Drouin, R. Development of a filter paper method potentially applicable to mass and high-risk urinary screenings for Fabry disease. J Inherit Metab Dis 30:106 (2007).
Auray-Blais, Co et al. Urinary globotriaosylceramide excretion correlates with the genotype in children and adults with Fabry disease. Mol Genet Metab 93:331-340(2008).
Mills, K. et al. Measurement of urinary CDH and CTH by tandem mass spectrometry in patients hemizygous and heterozygous for Fabry disease. J Inherit Metab Dis 28:35-48 (2005).
Schiffmann, R., Ries, M., Timmons, M., Flaherty, J. T. & Brady, R. O. Long-term therapy with agalsidase alfa for Fabry disease: safety and effects on renal function in a home infusion setting. Nephrol Dial Transplant 21:345-354 (2006).
Mehta, A. et al. Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey. Eur J Clin Invest 34:236-242 (2004).
Desnick, R. J. & Wasserstein, M. P. Fabry disease: clinical features and recent advances in enzyme replacment therapy. Adv Nephrol Necker Hosp 31:317-339 (2001).
Cho, M. E. & Kopp, J. B. Fabry disease in the era of enzyme replacement therapy: a renal perspective. Pediatr Nephrol 19: 583-593 (2004).
Eng, Co M. et al. Fabry disease: guidelines for the evaluation and management of multi-organ system involvement. Genet Med 8:539-548 (2006).
Warnock, D. G. Fabry disease: diagnosis and management, with emphasis on the renal manifestations. Curr Opin Nephrol Hypertens 14:87-95 (2005).
Meikle, P. J. et al. Diagnosis of lysosomal storage disorders: evaluation of lysosome-associated membrane protein LAMP-1 as a diagnostic marker. Clin Chem 43:1325-1335 (1997).
Tanaka, R., Sanada, S., Suzuki, M., Matsui, T. & Uoyama, Y. New method of screening chest radiography with computer analysis of respiratory kinetics. Nippon Hoshasen Gijutsu Gakkai Zasshi 58:665-669 (2002).
Meikle, P. J. et al. Newborn screening for lysosomal storage disorders. Mol Genet Metab 88:307-314(2006).
Kitagawa, T. et al. Non-invasive screening method for Fabry disease by measuring globotriaosylceramide in whole urine samples using tandem mass spectrometry. Mol Genet Metab 85:196-202(2005).
Spada, M. et al. High incidence of later-onset fabry disease revealed by newborn screening. Am J Hum Genet 79:31-40 (2006).
Boscaro, F. et al. Rapid quantitation of globotriaosylcerarnide in human plasma and urine: a potential application for monitoring enzyme replacement therapy in Anderson-Fabry disease. Rapid Commun Mass Spectrom 16:1507-1514(2002).
DOI : http://dx.doi.org/10.1007/s13273-010-0028-z [무료]
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