Plasmatic and urinary glycosaminoglycans characterization in Mucopolysaccharidosis II patient treated with enzyme-replacement therapy with idursulfate

We report the structural characterization of plasmatic and urinary GAGs in a patientaffected 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 about 90% delta Di4s and trace amounts of disulfated disaccharides. DS was also characterized as the main (about 90%) urinary GAG mainly composed of about 90% delta Di4s with minor percentages of monosulfated and disulfated disaccharides, in particular deltaDi2,4 dis. After 300 days of ERT, plasmatic DS strongly decreased but about 14% of IdoA-rich delta Di4s was still detected. Similarly, urinary galactosaminoglycans were mainly composed of 78% delta Di4s, about 11% delta Di6s, and about 4% delta Di0s with the persistence of delta Di2,4dis (about 4%). About 40% of IdoA-formed delta Di4s were also alculated, thus confirming that pathological DS is still present in excreted urinary GAGs during ERT. By considering the percentage 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 od 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 dirctly measured on products released by the activity of the recombinant enzyme Idursulfase, iduronate-2-sulfatase, evaluated using specific and sensitive analytical procedures