Serum Globotriaosylceramide Assay as a Screening Test for Fabry Disease in Patients with ESRD on Maintenance Dialysis in Korea
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Background/Aims: Fabry disease is an X-linked recessive and progressive disease caused by α-galactosidase A (α-GaL A) deficiency. We sought to assess the prevalence of unrecognized Fabry disease in dialysis-dependent patients and the efficacy of serum globotriaosylceramide (GL3) screening. Methods: A total of 480 patients of 1,230 patients among 17 clinics were enrolled. Serum GL3 levels were measured by tandem mass spectrometry. Additionally, we studied the association between increased GL3 levels and cardiovascular disease, cerebrovascular disease, or left ventricular hypertrophy. Results: Twenty-nine patients had elevated serum GL3 levels. The α-GaL A activity was determined for the 26 patients with high GL3 levels. The mean α-GaL A activity was 64.6 nmol/hr/mg (reference range, 45 to 85), and no patient was identified with decreased α-GaL A activity. Among the group with high GL3 levels, 15 women had a α-GaL A genetics analysis. No point mutations were discovered among the women with high GL3 levels. No correlation was observed between serum GL3 levels and α-GaL A activity; the Pearson correlation coefficient was 0.01352 (p = 0.9478). No significant correlation was observed between increased GL3 levels and the frequency of cardiovascular disease or cerebrovascular disease. Conclusions: Fabry disease is very rare disease in patients with end-stage renal disease. Serum GL3 measurements as a screening method for Fabry disease showed a high false-positive rate. Thus, serum GL3levels determined by tandem mass spectrometry may not be useful as a screening method for Fabry disease in patients with end stage renal disease. (Korean J Intern Med 2010;25:415-421)
Abstract
Background/Aims: Fabry disease is an X-linked recessive and progressive disease caused by α-galactosidase A (α-GaL A) deficiency. We sought to assess the prevalence of unrecognized Fabry disease in dialysis-dependent patients and the efficacy of serum globotriaosylceramide (GL3) screening. Methods: A total of 480 patients of 1,230 patients among 17 clinics were enrolled. Serum GL3 levels were measured by tandem mass spectrometry. Additionally, we studied the association between increased GL3 levels and cardiovascular disease, cerebrovascular disease, or left ventricular hypertrophy. Results: Twenty-nine patients had elevated serum GL3 levels. The α-GaL A activity was determined for the 26 patients with high GL3 levels. The mean α-GaL A activity was 64.6 nmol/hr/mg (reference range, 45 to 85), and no patient was identified with decreased α-GaL A activity. Among the group with high GL3 levels, 15 women had a α-GaL A genetics analysis. No point mutations were discovered among the women with high GL3 levels. No correlation was observed between serum GL3 levels and α-GaL A activity; the Pearson correlation coefficient was 0.01352 (p = 0.9478). No significant correlation was observed between increased GL3 levels and the frequency of cardiovascular disease or cerebrovascular disease. Conclusions: Fabry disease is very rare disease in patients with end-stage renal disease. Serum GL3 measurements as a screening method for Fabry disease showed a high false-positive rate. Thus, serum GL3levels determined by tandem mass spectrometry may not be useful as a screening method for Fabry disease in patients with end stage renal disease. (Korean J Intern Med 2010;25:415-421)
참고문헌 (23)
- Bekri S, "Fabry disease in patients with end-stage renal failure: the potential benefits of screening", Nephron Clin Pract, 101, pp.c33~c38 (2005)
- Rodriguez-Mari A, "Molecular analysis in Fabry disease in Spain: fifteen novel GLA mutations and identification of a homozygous female", Hum Mutat, 22, pp.258~ (2003)
- Mehta A, "Fabry disease defined: baseline clinical manifestations of 366 patients in the Fabry Outcome Survey", Eur J Clin Invest, 34, pp.236~242 (2004)
- Linthorst GE, "alpha-Galactosidase A deficiency in Dutch patients on dialysis: a critical appraisal of screening for Fabry disease", Nephrol Dial Transplant, 18, pp.1581~1584 (2003)
- Kotanko P, "Results of a nationwide screening for Anderson-Fabry disease among dialysis patients", J Am Soc Nephrol, 15, pp.1323~1329 (2004)
- Tsakiris D, "Report on management of renale failure in Europe, XXVI, 1995. Rare diseases in renal replacement therapy in the ERA-EDTA Registry", Nephrol Dial Transplant, 11(7), pp.4~20 (1996)
- Thadhani R, "Patients with Fabry disease on dialysis in the United States", Kidney Int, 61, pp.249~255 (2002)
- Nakao S, "Fabry disease: detection of undiagnosed hemodialysis patients and identification of a "renal variant" phenotype", Kidney Int, 64, pp.801~807 (2003)
- Nakao S, "An atypical variant of Fabry's disease in men with left ventricular hypertrophy", N Engl J Med, 333, pp.288~293 (1995)
- Meroni M, "Isolated glomerular proteinuria as the only clinical manifestation of Fabry's disease in an adult male", Nephrol Dial Transplant, 12, pp.221~223 (1997)
- Brenner BM, "Renoprotection by enzyme replacement therapy", Curr Opin Nephrol Hypertens, 13, pp.231~241 (2004)
- Desnick RJ, "Fabry disease, an underrecognized multisystemic disorder: expert recommendations for diagnosis, management, and enzyme replacement therapy", Ann Intern Med, 138, pp.338~346 (2003)
- Jin Ho Choi, "Short-Term Efficacy of Enzyme Replacement Therapy in Korean Patients with Fabry Disease", Journal of Korean Medical Science, 23(2), pp.243~250 (2008), 대한의학회
- Eng CM, "Fabry disease: baseline medical characteristics of a cohort of 1765 males and females in the Fabry Registry", J Inherit Metab Dis, 30, pp.184~192 (2007)
- Desnick RJ, "Fabry disease in childhood", J Pediatr, 144, pp.S20~S26 (2004)
- Fuller M, "Immunoquantification of alpha-galactosidase: evaluation for the diagnosis of Fabry disease", Clin Chem, 50, pp.1979~1985 (2004)
- Ginzburg L, "The pathogenesis of glycosphingolipid storage disorders", Semin Cell Dev Biol, 15, pp.417~431 (2004)
- Pastores GM, "Biochemical and molecular genetic basis of Fabry disease", J Am Soc Nephrol, 13, pp.S130~133 (2002)
- Nelson BC, "Globotriaosylceramide isoform profiles in human plasma by liquid chromatographytandem mass spectrometry", J Chromatogr B Analyt Technol Biomed Life Sci, 805, pp.127~134 (2004)
- Mills K, "Synthesis of novel internal standards for the quantitative determination of plasma ceramide trihexoside in Fabry disease by tandem mass spectrometry", FEBS Lett, 515, pp.171~176 (2002)
- Young E, "Is globotriaosylceramide a useful biomarker in Fabry disease?", Acta Paediatr Suppl, 94, pp.51~54 (2005)
- Yoon HR, "Determination of plasma C16-C24 globotriaosylceramide (Gb3) isoforms by tandem mass spectrometry for diagnosis of Fabry disease", J Genet Med, 4, pp.45~52 (2007)
- Forni S, "Falsely elevated urinary Gb3 (globotriaosylceramide, CTH, GL3)", Mol Genet Metab, 97, pp.91~ (2009)