title: Glycan-based biomarkers for mucopolysaccharidoses.
abstract: The mucopolysaccharidoses (MPS) result from attenuation or loss of enzyme activities required for lysosomal degradation of the glycosaminoglycans, hyaluronan, heparan sulfate, chondroitin/dermatan sulfate, and keratan sulfate. This review provides a summary of glycan biomarkers that have been used to characterize animal models of MPS, for diagnosis of patients, and for monitoring therapy based on hematopoietic stem cell transplantation and enzyme replacement therapy. Recent advances have focused on the non-reducing terminus of the glycosaminoglycans that accumulate as biomarkers, using a combination of enzymatic digestion with bacterial enzymes followed by quantitative liquid chromatography/mass spectrometry. These new methods provide a simple, rapid diagnostic strategy that can be applied to samples of urine, blood, cerebrospinal fluid, cultured cells and dried blood spots from newborn infants. Analysis of the non-reducing end glycans provides a method for monitoring enzyme replacement and substrate reduction therapies and serves as a discovery tool for uncovering novel biomarkers and new forms of mucopolysaccharidoses.
authors: Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California San Diego, La Jolla, CA 92093, USA.
authors: Roger
authors: R
authors: Lawrence
authors: Zacharon Pharmaceuticals, Inc., San Diego, CA 92121, USA.
authors: Jillian R
authors: JR
authors: Brown
authors: Genetic Disease Screening Program, California Department of Public Health, Richmond, CA 94804, USA.
authors: Fred
authors: F
authors: Lorey
authors: Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA 90502, USA.
authors: Patricia I
authors: PI
authors: Dickson
authors: Zacharon Pharmaceuticals, Inc., San Diego, CA 92121, USA. Electronic address: bcrawford@bmrn.com.
authors: Brett E
authors: BE
authors: Crawford
authors: Department of Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California San Diego, La Jolla, CA 92093, USA. Electronic address: jesko@ucsd.edu.
authors: Jeffrey D
authors: JD
authors: Esko
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000737:chemistry; D002853:Chromatography, Liquid; D004195:Disease Models, Animal; D059788:Dried Blood Spot Testing; D057075:Enzyme Assays; D056947:Enzyme Replacement Therapy; D006025:Glycosaminoglycans / Q000097:blood / Q000134:cerebrospinal fluid / Q000737:chemistry* / Q000652:urine; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007118:Immunoassay; D007231:Infant, Newborn; D013058:Mass Spectrometry; D009083:Mucopolysaccharidoses / Q000097:blood / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000628:therapy / Q000652:urine; D010084:Oxidation-Reduction
chemical_list: D015415:Biomarkers; D006025:Glycosaminoglycans
keywords: Carbohydrate biomarkers; Glycosaminoglycans; Lysosomal storage disorders; Mass spectrometry; Mucopolysaccharidoses; Sensi-Pro assay
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