title: Plasmatic and Urinary Glycosaminoglycans Characterization in Mucopolysaccharidosis II Patient Treated with Enzyme-Replacement Therapy with Idursulfase.
abstract: We report the structural characterization of plasmatic and urinary GAGs in a patient affected by MPS II (Hunter syndrome) before and during the first 10 months of enzyme-replacement therapy (ERT). Plasmatic GAGs before ERT were rich in pathological DS consisting of iduronic acid (IdoA) and composed of ~90% ΔDi4s and trace amounts of disulfated disaccharides. DS was also characterized as the main (~90%) urinary GAG mainly composed of ~90% ΔDi4s with minor percentages of monosulfated and disulfated disaccharides, in particular ΔDi2,4dis. After 300 days of ERT, plasmatic DS strongly decreased but ~14% of IdoA-rich ΔDi4s was still detected. Similarly, urinary galactosaminoglycans were mainly composed of 78% ΔDi4s, ~11% ΔDi6s and ~4% ΔDi0s with the persistence of ΔDi2,4dis (~4%). About 40% of IdoA-formed ΔDi4s were also calculated, thus confirming that pathological DS is still present in excreted urinary GAGs during ERT. By considering the % of IdoA, we observed rather similar kinetics of excretion in fluids from the beginning of the treatment. Immediately after the first enzyme infusion, a large amount of abnormal DS is removed from tissues reaching the blood compartment and eliminated via the urine, and this process lasts for about 2 weeks. After this, the percentage of IdoA-rich material present in biological fluids remains fairly constant over the following 9 months of treatment. To date, these are the first data regarding plasmatic and urinary kinetics directly measured on products released by the activity of the recombinant enzyme Idursulfase, iduronate-2-sulfatase, evaluated using specific and sensitive analytical procedures.
authors: Pediatric Division, Department of Clinical Sciences, Polytechnic University of the Marche, Ospedali Riuniti, Presidio Salesi, Ancona, Italy.
authors: Giovanni V
authors: GV
authors: Coppa
authors: Dania
authors: D
authors: Buzzega
authors: Lucia
authors: L
authors: Zampini
authors: Francesca
authors: F
authors: Maccari
authors: Lucia
authors: L
authors: Santoro
authors: Fabio
authors: F
authors: Galeotti
authors: Tiziana
authors: T
authors: Galeazzi
authors: Orazio
authors: O
authors: Gabrielli
authors: Nicola
authors: N
authors: Volpi