title: 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.
authors.affiliation: Division of Nephrology, University Hospital, Zürich, Switzerland. akistler@med.miami.edu
authors.forename: Andreas D
authors.initials: AD
authors.lastname: Kistler
authors.forename: Justyna
authors.initials: J
authors.lastname: Siwy
authors.forename: Frank
authors.initials: F
authors.lastname: Breunig
authors.forename: Praveen
authors.initials: P
authors.lastname: Jeevaratnam
authors.forename: Alexander
authors.initials: A
authors.lastname: Scherl
authors.forename: William
authors.initials: W
authors.lastname: Mullen
authors.forename: David G
authors.initials: DG
authors.lastname: Warnock
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.forename: Derralynn A
authors.initials: DA
authors.lastname: Hughes
authors.forename: Harald
authors.initials: H
authors.lastname: Mischak
authors.forename: Rudolf P
authors.initials: RP
authors.lastname: Wüthrich
authors.forename: Andreas L
authors.initials: AL
authors.lastname: Serra
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine*; D016022:Case-Control Studies; D019075:Electrophoresis, Capillary; D056947:Enzyme Replacement Therapy; D000795:Fabry Disease / Q000188:drug therapy / Q000652:urine*; D005260:Female; D006801:Humans; D013058:Mass Spectrometry; D008875:Middle Aged; D000519:alpha-Galactosidase / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D000519:alpha-Galactosidase