The two Fabry patients from the validation cohort with false-negative proteomic test results did not obviously differ from the remaining patients, in particular they had both GLA mutations which were not unique in the cohort. To further evaluate the specificity of the biomarker model for Fabry disease as compared to other disorders, we applied it to a total of 412 previously analyzed urine probes from female patients suffering from a wide variety of renal, metabolic and cardiovascular diseases. The overall specificity of the model applied to these 412 patients was 97%, i.e. the rate of false positive results for Fabry disease among patients with other diseases was very low. To gain insight into pathophysiologic mechanisms, we attempted to identify the peptides with altered excretion in Fabry disease. Because the small sample volume used for capillary Ruxolitinib electrophoresis is not usually sufficient for tandem mass spectrometry based sequencing, we used liquid chromatography-tandem mass spectrometry for peptide sequencing. We were able to identify the amino acid sequence of 50 out of all 152 differentially excreted peptides, and among the 64 markers used in the diagnostic model, 13 could be identified. The peptide sequences of all identified markers are given along with their CE-MS characteristics in Table S1. The majority of identified regulated peptides were collagen fragments with 2/3 of them being up- and 1/3 being downregulated. Interestingly, the C-terminal sequences PPG and PGP were very frequent among the upregulated fragments, whereas they were hardly present among the downregulated. To analyze the effects of enzyme replacement therapy on the urine proteome in Fabry disease, we analyzed spot urine samples of 11 female Fabry patients that were receiving ERT. The clinical characteristics of these patients are summarized in Table 1. CT99021 in vivo Notably, the treated patients did not differ significantly in terms of their clinical parameters from the untreated patients except for a higher rate of reported acroparesthesia. In particular, GFR, albuminuria and LVMI were not significantly different.