21faf50d435b0bfc433f47ed0a6dc2f6 pmc_33924567.pdf d9fa6f7c1e6209adf5c5ba08ecf463588d7e4de6 pmc_33924567.pdf 18deaa5cc4d3b91575528060dba7c62c1bb91033bc30e8a296ed19cb1f424bc1 pmc_33924567.pdf Title: Biomarkers in Fabry Disease. Implications for Clinical Diagnosis and Follow-Up Subject: Fabry disease (FD) is a lysosomal storage disorder caused by deficient alpha-galactosidase A activity in the lysosome due to mutations in the GLA gene, resulting in gradual accumulation of globotriaosylceramide and other derivatives in different tissues. Substrate accumulation promotes different pathogenic mechanisms in which several mediators could be implicated, inducing multiorgan lesions, mainly in the kidney, heart and nervous system, resulting in clinical manifestations of the disease. Enzyme replacement therapy was shown to delay disease progression, mainly if initiated early. However, a diagnosis in the early stages represents a clinical challenge, especially in patients with a non-classic phenotype, which prompts the search for biomarkers that help detect and predict the evolution of the disease. We have reviewed the mediators involved in different pathogenic mechanisms that were studied as potential biomarkers and can be easily incorporated into clinical practice. Some accumulation biomarkers seem to be useful to detect non-classic forms of the disease and could even improve diagnosis of female patients. The combination of such biomarkers with some response biomarkers, may be useful for early detection of organ injury. The incorporation of some biomarkers into clinical practice may increase the capacity of detection compared to that currently obtained with the established diagnostic markers and provide more information on the progression and prognosis of the disease. Keywords: fabry disease; classic phenotype; late-onset phenotype; biomarkers; cardiomyopathy; chronic kidney disease; vasculopathy; lyso-Gb3; Gb3; inflammatory response Author: Clara Carnicer-Cáceres, Jose Antonio Arranz-Amo, Cristina Cea-Arestin, Maria Camprodon-Gomez, David Moreno-Martinez, Sara Lucas-Del-Pozo, Marc Moltó-Abad, Ariadna Tigri-Santiña, Irene Agraz-Pamplona, Jose F Rodriguez-Palomares, Jorge Hernández-Vara, Mar Armengol-Bellapart, Mireia del-Toro-Riera and Guillem Pintos-Morell Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Apr 14 04:35:29 2021 CEST ModDate: Wed Apr 14 04:38:29 2021 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 18 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2438148 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- WNGAPW+VnURWPalladioL Type 1 Custom yes yes no 10 0 PCWCLJ+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 YYFFWO+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 LHWIEE+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 ENXZUH+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 XPUSBJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 36 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 39 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 61 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 65 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 69 0 QDCWHF+EURM10 Type 1 Builtin yes yes no 87 0 FVGTFK+CMSY10 Type 1 Builtin yes yes no 125 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 03:19:51 CEST RepresentationInformation: pmc_33924567.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 12:09:52 CEST Size: 2438148 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 542 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Pathogenesis Destination: section.2 Item: Title: Markers of Fabry Disease Destination: section.3 Children: Item: Title: Clinical Markers Destination: subsection.3.1 Item: Title: New Markers. Candidate Severity and Predictive Biomarkers in Fabry Disease Destination: subsection.3.2 Children: Item: Title: Accumulation Biomarkers Destination: subsubsection.3.2.1 Item: Title: Response Biomarkers Destination: subsubsection.3.2.2 Item: Title: Future Lines of Work Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Biomarkers in Fabry Disease. Implications for Clinical Diagnosis and Follow-Up Author: Clara Carnicer-Cáceres, Jose Antonio Arranz-Amo, Cristina Cea-Arestin, Maria Camprodon-Gomez, David Moreno-Martinez, Sara Lucas-Del-Pozo, Marc Moltó-Abad, Ariadna Tigri-Santiña, Irene Agraz-Pamplona, Jose F Rodriguez-Palomares, Jorge Hernández-Vara, Mar Armengol-Bellapart, Mireia del-Toro-Riera and Guillem Pintos-Morell Subject: Fabry disease (FD) is a lysosomal storage disorder caused by deficient alpha-galactosidase A activity in the lysosome due to mutations in the GLA gene, resulting in gradual accumulation of globotriaosylceramide and other derivatives in different tissues. Substrate accumulation promotes different pathogenic mechanisms in which several mediators could be implicated, inducing multiorgan lesions, mainly in the kidney, heart and nervous system, resulting in clinical manifestations of the disease. Enzyme replacement therapy was shown to delay disease progression, mainly if initiated early. However, a diagnosis in the early stages represents a clinical challenge, especially in patients with a non-classic phenotype, which prompts the search for biomarkers that help detect and predict the evolution of the disease. We have reviewed the mediators involved in different pathogenic mechanisms that were studied as potential biomarkers and can be easily incorporated into clinical practice. Some accumulation biomarkers seem to be useful to detect non-classic forms of the disease and could even improve diagnosis of female patients. The combination of such biomarkers with some response biomarkers, may be useful for early detection of organ injury. The incorporation of some biomarkers into clinical practice may increase the capacity of detection compared to that currently obtained with the established diagnostic markers and provide more information on the progression and prognosis of the disease. Keywords: fabry disease; classic phenotype; late-onset phenotype; biomarkers; cardiomyopathy; chronic kidney disease; vasculopathy; lyso-Gb3; Gb3; inflammatory response Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Wed Apr 14 04:35:29 CEST 2021 ModDate: Wed Apr 14 04:38:29 CEST 2021 ID: 0xdcceac5642e0ec59b85927db87a43324, 0xdcceac5642e0ec59b85927db87a43324 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: YYFFWO+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 241 FontDescriptor: FontName: YYFFWO+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: QDCWHF+EURM10 FontSubset: true FirstChar: 11 LastChar: 12 FontDescriptor: FontName: QDCWHF+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: LHWIEE+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: LHWIEE+URWPalladioL-Roma Flags: Symbolic 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