title: Mental retardation in mucopolysaccharidoses correlates with high molecular weight urinary heparan sulphate derived glucosamine.
abstract: Mucopolysaccharidoses (MPS) are characterized by mental retardation constantly present in the severe forms of Hurler (MPS I), Hunter (MPS II) and Sanfilippo (MPS III) diseases. On the contrary, mental retardation is absent in Morquio (MPS IV) and Maroteaux-Lamy (MPS VI) diseases and absent or only minimal in the attenuated forms of MPS I, II and III. Considering that MPS patients affected by mental disease accumulate heparan sulfate (HS) due to specific enzymatic defects, we hypothesized a possible correlation between urinary HS-derived glucosamine (GlcN) accumulated in tissues and excreted in biological fluids and mental retardation. 83 healthy subjects were found to excrete HS in the form of fragments due to the activity of catabolic enzymes that are absent or impaired in MPS patients. On the contrary, urinary HS in 44 patients was observed to be composed of high molecular weight polymer and fragments of various lengths depending on MPS types. On this basis we correlated mental retardation with GlcN belonging to high and low molecular weight HS. We demonstrate a positive relationship between the accumulation of high molecular weight HS and mental retardation in MPS severe compared to attenuated forms. This is also supported by the consideration that accumulation of other GAGs different from HS, as in MPS IV and MPS VI, and low molecular weight HS fragments do not impact on central nervous system disease.
authors.affiliation: Pediatric Division, Department of Clinical Sciences, Polytechnic University of the Marche, Ospedali Riuniti, Presidio Salesi, Ancona, Italy.
authors.forename: G V
authors.initials: GV
authors.lastname: Coppa
authors.affiliation: Pediatric Division, Department of Clinical Sciences, Polytechnic University of the Marche, Ospedali Riuniti, Presidio Salesi, Ancona, Italy.
authors.forename: O
authors.initials: O
authors.lastname: Gabrielli
authors.affiliation: Pediatric Division, Department of Clinical Sciences, Polytechnic University of the Marche, Ospedali Riuniti, Presidio Salesi, Ancona, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Zampini
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 213/D, 41125, Modena, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Maccari
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 213/D, 41125, Modena, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Mantovani
authors.affiliation: Pediatric Division, Department of Clinical Sciences, Polytechnic University of the Marche, Ospedali Riuniti, Presidio Salesi, Ancona, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Galeazzi
authors.affiliation: Pediatric Division, Department of Clinical Sciences, Polytechnic University of the Marche, Ospedali Riuniti, Presidio Salesi, Ancona, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Santoro
authors.affiliation: Pediatric Division, Department of Clinical Sciences, Polytechnic University of the Marche, Ospedali Riuniti, Presidio Salesi, Ancona, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Padella
authors.affiliation: Pediatric Division, Department of Clinical Sciences, Polytechnic University of the Marche, Ospedali Riuniti, Presidio Salesi, Ancona, Italy.
authors.forename: R L
authors.initials: RL
authors.lastname: Marchesiello
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 213/D, 41125, Modena, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Galeotti
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 213/D, 41125, Modena, Italy. volpi@unimo.it.
authors.forename: N
authors.initials: N
authors.lastname: Volpi
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D005944:Glucosamine / Q000737:chemistry / Q000652:urine*; D006497:Heparan Sulfate / Q000737:chemistry / Q000652:urine*; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D009083:Mucopolysaccharidoses / Q000235:genetics* / Q000523:psychology*; D008059:Mucopolysaccharidosis I / Q000235:genetics / Q000523:psychology; D009084:Mucopolysaccharidosis III / Q000235:genetics / Q000523:psychology; D012016:Reference Values; D055815:Young Adult
chemical_list: D005944:Glucosamine; D006497:Heparan Sulfate
keywords: Glucosamine; Glycosaminoglycans; Heparan sulfate; Mental retardation; Mucopolysaccharidosis