Bachground: MPS1 is an autosomal recessive disorder caused by deficient activity of the lysosomal enzyme alpha-L iduronidase, which leads to accumulation of heparan sulfate and dermatan sulfate, resulting in progressive multisystem disease with respiratory, skeletal, and neurologic manifestations. Treatment for MPS1 consists of supportive care and enzyme-replacement therapy with Laronidase. Bone marrow and hematopoietic stem cell transplantation is the treatment of choice for patients suffering from MPS1 with no or minimal central nervous system manifestation. Case Report: A 50 month old Iranian boy with coarse facial features, prominent forehead, corneal cloudy, sleep disturbance, hepatosplenomegaly, inguinal hernia, joint stiffness, and dysostosis multiplex congenital. He was diagnosed with MPS1 on the basis of clinical findings, an elevated urinary glycosaminoglycan level and low alpha-L-iduronidase activity in leukocytes. Mutation analysis revealed a homozygous splice mutation in the IDUA gene. He has been started on injection of aldurozyme intravenously every week from age 26 months. To attempt to prevent neurological impairment before bone marrow transplantation, he receives intrathecal enzyme replacement of aldurozyme and samples of his CSF are obtained for testing monthly. He tolerates intrathecal ERT with no adverse events. At age 50 months he will receive a bone marrow transplantation. Mucopolysaccharidosis I(MPS I)is a lysosomal disease caused by αiduronidase deficiency, leading to glycosaminoglycans(GAGs)storage in several organs.This may affect the vertebrae and meninges and cause spinal cord compression (SCC).As intravenous enzyme replacement therapy (ERT)is not expected to cross the blood-brain barrier,other approaches of drug delivery are necessary to treat SCC.We report a case of a 23 yo MPS I patient(Hurler-Scheie phenotype)with SCC who choose to stop intravenous ERT after 5 years of treatment since his perception was that symptoms were not improving.Laminectomy and occipital craniotomy were then performed, again with no improvement of his condition.Intrathecal infusions were offered on a compassionate use basis,and he agreed to perform 4 infusions with one month intervals.At the baseline and after the 4th infusion,CSF biochemistry(with GAGs measurement),clinical neurology assessments and some additional studies were performed.The patient referred improvement of his lower limbs sensitivity every first week after infusions with regression to previous status thereafter.Somatic sensitive potentials in upper and lower limbs showed improvement Intrathecal infusions showed to be safe and may be offered as an option when the neurosurgical risk is high or as an alternative to improve patient's QOL. We think that adjustments in dosis and infusion frequency may improve outcome of this approach.