A distinct urinary biomarker pattern characteristic of female fabry patients that mirrors response to enzyme replacement therapy

Kistler, A.D. et al. (2011) A distinct urinary biomarker pattern characteristic of female fabry patients that mirrors response to enzyme replacement therapy. PLoS ONE, 6(6), e20534. (doi: 10.1371/journal.pone.0020534)

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Publisher's URL: http://dx.doi.org/10.1371/journal.pone.0020534

Abstract

Female patients affected by Fabry disease, an X-linked lysosomal storage disorder, exhibit a wide spectrum of symptoms, which renders diagnosis, and treatment decisions challenging. No diagnostic test, other than sequencing of the alpha-galactosidase A gene, is available and no biomarker has been proven useful to screen for the disease, predict disease course and monitor response to enzyme replacement therapy. Here, we used urine proteomic analysis based on capillary electrophoresis coupled to mass spectrometry and identified a biomarker profile in adult female Fabry patients. Urine samples were taken from 35 treatment-naive female Fabry patients and were compared to 89 age-matched healthy controls. We found a diagnostic biomarker pattern that exhibited 88.2% sensitivity and 97.8% specificity when tested in an independent validation cohort consisting of 17 treatment-naive Fabry patients and 45 controls. The model remained highly specific when applied to additional control patients with a variety of other renal, metabolic and cardiovascular diseases. Several of the 64 identified diagnostic biomarkers showed correlations with measures of disease severity. Notably, most biomarkers responded to enzyme replacement therapy, and 8 of 11 treated patients scored negative for Fabry disease in the diagnostic model. In conclusion, we defined a urinary biomarker model that seems to be of diagnostic use for Fabry disease in female patients and may be used to monitor response to enzyme replacement therapy

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mullen, Dr Bill and Mischak, Professor Harald
Authors: Kistler, A.D., Siwy, J., Breunig, F., Jeevaratnam, P., Scherl, A., Mullen, W., Warnock, D.G., Wanner, C., Hughes, D.A., Mischak, H., Wüthrich, R.P., and Serra, A.L.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203
Published Online:15 June 2011
Copyright Holders:Copyright © 2011 The Authors
First Published:First published in PLoS ONE 6(6):e20534
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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