Kistler, AD;
Siwy, J;
Breunig, F;
Jeevaratnam, P;
Scherl, A;
Mullen, W;
Warnock, DG;
... Serra, AL; + view all
(2011)
A Distinct Urinary Biomarker Pattern Characteristic of Female Fabry Patients That Mirrors Response to Enzyme Replacement Therapy.
PLOS ONE
, 6
(6)
, Article e20534. 10.1371/journal.pone.0020534.
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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.
| Type: | Article |
|---|---|
| Title: | A Distinct Urinary Biomarker Pattern Characteristic of Female Fabry Patients That Mirrors Response to Enzyme Replacement Therapy |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0020534 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0020534 |
| Language: | English |
| Additional information: | © 2011 Kistler et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding for this study was supported by unrestricted research grants provided by Genzyme (to ADK, RPW and ALS), Shire (to ADK, RPW and ALS) and Amgen (to RPW) and a European Community's 7th Framework Programme grant (to HM; grant agreement HEALTH-F2-2009-241544 (SysKID)). The funders had no role in study design, data collection and analysis, or preparation of the manuscript. |
| Keywords: | CHRONIC KIDNEY-DISEASE, ONSET HYPERTROPHIC CARDIOMYOPATHY, MASS-SPECTROMETRY, ALPHA-GALACTOSIDASE, HEMODIALYSIS-PATIENTS, CLINICAL PROTEOMICS, YOUNG-PATIENTS, DISCOVERY, GLOBOTRIAOSYLCERAMIDE, PREVALENCE |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Haematology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1315247 |
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