A Distinct Urinary Biomarker Pattern Characteristic of Female Fabry Patients That Mirrors Response to Enzyme Replacement Therapy

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-naïve 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-naïve 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.

Urinary Proteomics and Precision Medicine for Chronic Kidney Disease: Current Status and Future Perspectives

“…It was also possible in patients with renal affection due to Fabry's disease to demonstrate changes in their urinary proteomic peptide pattern in the direction of normalization after treatment with enzyme replacement therapy in agreement with the concept that the treatment had impact on the pathogenetic pathway.…”

Fabry Nephropathy: An Evidence-Based Narrative Review

“…An approach using urine proteomic analysis based on capillary electrophoresis coupled to mass spectrometry identified a distinct peptide profile in the urine that characterized adult female Fabry patients. The pattern was able to distinguish female Fabry patients from healthy controls and from patients with various other forms of kidney or systemic diseases [61]. In this regard, it is considered that urinary Gb3 levels in the high range, as usually seen in classical males, can differentiate between classical FD and other diseases.…”

Fabry nephropathy: a review – how can we optimize the management of Fabry nephropathy?

“…In 35 treatment-naïve adult female patients with Fabry disease an abnormal urine profile was identified, which was almost completely corrected following ERT [106]. A further two protein biomarkers have been identified in the urine of children with Fabry disease and type-1 diabetes using label-free quantitative proteomics.…”