title: Elevated cerebral spinal fluid biomarkers in children with mucopolysaccharidosis I-H.
abstract: Mucopolysaccharidosis (MPS) type-IH is a lysosomal storage disease that results from mutations in the IDUA gene causing the accumulation of glycosaminoglycans (GAGs). Historically, children with the severe phenotype, MPS-IH (Hurler syndrome) develop progressive neurodegeneration with death in the first decade due to cardio-pulmonary complications. New data suggest that inflammation may play a role in MPS pathophysiology. To date there is almost no information on the pathophysiologic changes within the cerebral spinal fluid (CSF) of these patients. We evaluated the CSF of 25 consecutive patients with MPS-IH. While CSF glucose and total protein were within the normal range, we found a significantly mean elevated CSF opening pressure at 24 cm H2O (range 14-37 cm H2O). We observed a 3-fold elevation in CSF heparan sulfate and a 3-8 fold increase in MPS-IH specific non-reducing ends, I0S0 and I0S6. Cytokine analyses in CSF of children with MPS-IH showed significantly elevated inflammatory markers including: MCP-1 SDF-1a, IL-Ra, MIP-1b, IL-8, and VEGF in comparison to unaffected children. This is the largest report of CSF characteristics in children with MPS-IH. Identification of key biomarkers may provide further insight into the inflammatory-mediated mechanisms related to MPS diseases and perhaps lead to improved targeted therapies.
authors.affiliation: Division of Pediatric Neurology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Gerald V
authors.initials: GV
authors.lastname: Raymond
authors.affiliation: University of Utah, School of Medicine, Department of Pathology, Salt Lake City, UT, USA.
authors.forename: Marzia
authors.initials: M
authors.lastname: Pasquali
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Los Angeles, CA, USA.
authors.forename: Lynda E
authors.initials: LE
authors.lastname: Polgreen
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Los Angeles, CA, USA.
authors.forename: Patricia I
authors.initials: PI
authors.lastname: Dickson
authors.affiliation: Division of Pediatric Blood and Marrow Transplant, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Weston P
authors.initials: WP
authors.lastname: Miller
authors.affiliation: Division of Pediatric Blood and Marrow Transplant, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Orchard
authors.affiliation: Division of Pediatric Blood and Marrow Transplant, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Troy C
authors.initials: TC
authors.lastname: Lund
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000134:cerebrospinal fluid / Q000235:genetics; D000293:Adolescent; D015415:Biomarkers / Q000134:cerebrospinal fluid; D015170:Cerebrospinal Fluid Pressure; D018932:Chemokine CCL2 / Q000134:cerebrospinal fluid / Q000235:genetics; D054377:Chemokine CXCL12 / Q000134:cerebrospinal fluid / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression; D005947:Glucose / Q000134:cerebrospinal fluid; D006497:Heparan Sulfate / Q000134:cerebrospinal fluid*; D006801:Humans; D007068:Iduronidase / Q000134:cerebrospinal fluid / Q000172:deficiency / Q000235:genetics*; D007223:Infant; D016209:Interleukin-8 / Q000134:cerebrospinal fluid / Q000235:genetics; D008297:Male; D008059:Mucopolysaccharidosis I / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000134:cerebrospinal fluid / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D018932:Chemokine CCL2; D054377:Chemokine CXCL12; D005947:Glucose; D006497:Heparan Sulfate; D007068:Iduronidase; D016209:Interleukin-8; D009419:Nerve Tissue Proteins; C111835:CCL2 protein, human; C515255:CXCL12 protein, human; C493277:MAPKAP1 protein, human; C000615655:IDUA protein, human