Effect of 6 years 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 two-week period of enzyme infusion, GAGs in urine and plasma were analyzed in two patients with 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 (about 13,000-13,500) consisting of about 75-78% iduronic acid and rich in 4-sulphated disaccharides (deltaDi4s) and attributable to DS. Furthermore, a high amount of this GAG was dirctly 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 sulphate and of DS. On the contrary, a plysaccharide possessing a high molecular mass, about 11,500-12,000, lower than the polymer extracted before ERT but slightly higer than the controls (about 11,000), was found in the urine of both patients. This macromolecule was characterized as a mixture of DS/chondroitin sulfated based on the high percentage of 4-suphated disaccharide (4s/6s ratio of about 3.1) and iduronic acid (about 60%). These results are indicative of the incapacity of ERT at tha standard dose to definitively eliminate DS from the urine. Finally, a variable effect of ERT depending on each administration was also observed.