Effect of 12 years of enzyme replacement therapy on plasma and urine glycosaminoglycans in attenuated Mucopolysaccharidosis I patients

Backgroung To date, only few data are available on the capacity of ERT at standard doses to definitively eliminate pathological glycosaminoglycans (GAGs). We report a characterization of urine and plasma GAGs performed in order to assess the effect of ERT after 12 years in two attenuated MPS I siblings. Case Study or Methods The brother (sibling1) commenced weekly laronidase infusions at a dose of 0.5 mg/kg at the age of 5 months and the sister (sibling 2) at the age of 5 years, shortly after the diagnosis. Urine samples were analyzed by DMB and electrophoretic methods. Plasma GAG disaccharides were evaluated by HPLC. Results Sibling 1. Total urinary GAGs excretion was slightly above the upper normal limits for age during the last 6 years. Urinary GAGs electrophoresis showed the presence of DS and CS with a ratio of about 50/50. Plasma GAGs before ERT were 18.2 μg/ml (nv 5.2 ± 3.01) with a CS/DS ratio of 25/75 (nv 100/0). After 12 years of ERT, plasma GAGs have remained within the normal range for age, with traces of DS. Sibling2. Total urinary GAGs excretion was elevated before ERT and normalized after 4 months of therapy until 8.5 years of age. At the age of 10.5 years GAGs levels increased to 89 μg/creat (nv 37 ± 18) and subsequently normalized. Urinary GAGs were characterized by the presence of DS and HS before ERT and normalized after 4 months of ERT up to the age of 6 years when a ratio of 50/50 of DS/CS was observed. Plasma GAGs at the age of 11.5 years were 2.8 μg/ml (nv 2.7 ± 1.12) with a CS/DS ratio of 98/2 (nv 100/0). Discussion Biochemical observation of these siblings reveals a moderate increase of total urinary GAGs and more notably DS later in childhood. Normal levels of plasmatic GAGs were observed with only traces of DS. No abnormal levels of HS present before ERT were detected in urine and plasma. Based on the present results, we can suppose that the amount of supplied enzyme could contribute to the insufficient GAGs degradation.