Effect of 6 years of enzyme replacement therapy on plasma and urine glycosaminoglycans in attenuated MPS I patients.
Enzyme-replacement therapy (ERT) is a new option for the clinical management of MPS I. However, no detailed data are available on the structural characterization of glycosaminoglycans (GAGs) in the urine and plasma of patients before ERT and during treatment regimens. Before ERT and over a two-week period of enzyme infusion, GAGs in urine and plasma were analyzed in two patients with the Hurler-Scheie form of MPS I subjected to ERT for 6 years. In both patients before ERT, high amounts of a GAG were found in the urine, composed in particular of a high molecular mass polymer (approximately 13,000-13,500) consisting of approximately 75-78% iduronic acid and rich in 4-sulfated disaccharides (DeltaDi4s) and attributable to DS. Furthermore, a high amount of this GAG was directly detected in the blood. Plasma GAGs in MPS I patients subjected to ERT were found to be comparable to those of normal subjects with the absence of heparan sulfate and of DS. On the contrary, a polysaccharide possessing a high molecular mass, approximately 11,500-12,000, lower than the polymer extracted before ERT but slightly higher than the controls (approximately 11,000), was found in the urine of both patients. This macromolecule was characterized as a mixture of DS/chondroitin sulfate based on the high percentage of 4-sulfated disaccharide (4s/6s ratio of approximately 3.1) and iduronic acid ( approximately 60%). These results are indicative of the incapacity of ERT at the standard dose to definitively eliminate DS from the urine. Finally, a variable effect of ERT depending on each administration was also observed.
Pediatric Division, Department of Clinical Sciences, Polytechnic University of the Marche, Ospedali Riuniti, Presidio Salesi, Ancona, Italy.
Giovanni V
GV
Coppa
Dania
D
Buzzega
Lucia
L
Zampini
Francesca
F
Maccari
Tiziana
T
Galeazzi
Francesca
F
Pederzoli
Orazio
O
Gabrielli
Nicola
N
Volpi
D015415:Biomarkers / Q000097:blood* / Q000652:urine*; D016022:Case-Control Studies; D004187:Disaccharides / Q000652:urine; D056947:Enzyme Replacement Therapy; D006025:Glycosaminoglycans / Q000097:blood* / Q000652:urine*; D006801:Humans; D008059:Mucopolysaccharidosis I / Q000097:blood* / Q000628:therapy / Q000652:urine*
D015415:Biomarkers; D004187:Disaccharides; D006025:Glycosaminoglycans