Hematopoietic stem cell transplantation (HSCT) in children with mucopolysaccharidosis type I (MPS I) involves replacing their deficient macrophages with ones that produce normal amounts of enzyme. [Weisstein: 2004] [Souillet: 2003] [Gassas: 2003] The success rate of HSCT depends upon several factors, such as the age of the patient and degree of cardiopulmonary involvement at time of transplant. Successful HSCT increases survival, reduces cognitive decline, facial coarseness and hepatosplenomegaly, improves hearing, and maintains normal heart function; however, the skeletal and joint manifestations, carpel tunnel syndrome manifestations, and corneal clouding continue to progress unabated.

Neuropsychological responses to HSCT are related to the age and intellectual capacity of the child at the time of the engraftment. If HSCT is done before evidence of significant developmental delay (usually under 2 years), there is some success in decreasing the degree and rate of cognitive decline. Children showing significant cognitive impairment prior to undergoing HSCT do not appear to benefit developmentally. As with any HSCT, there is a risk of graft-versus-host disease and up to a 20% risk of mortality. The use of ERT before HSCT might improve the clinical signs and symptoms (e.g., severe cardiomyopathy), which results in less transplantation-related complications. [Cox-Brinkman: 2006]

Enzyme replacement therapy (ERT)involves intravenous administration of recombinant alpha-L-iduronidase enzyme (Aldurazyme) to assist in the breakdown of accumulated GAGs and prevent further buildup. [Muenzer: 2004] [Wraith: 2005] [Wraith: 2004] Significant reduction in liver size, decrease in joint restriction, improvement in breathing and sleep apnea, and increased distance walked in the 6-minute walk test were demonstrated in individuals with attenuated MPS I. The benefit of ERT in those with severe disease has not been assessed. Because the recombinant enzyme is not thought to cross the blood-brain barrier, the best option to reduce the risk of cognitive impairment in those with severe MPS I remains early initiation of HSCT. As with HSCT, ERT does not appear to have significant beneficial effects on bone disease or corneal clouding.

The current dosing regimen for Aldurazyme involves premedication with anti-inflammatory and antihistamine drugs and intravenous weekly infusion of 100 units (0.58 mg)/kg of Aldurazyme over 4 hours. Although antibodies were present in all study patients in the clinical trials, they are not neutralizing and no known clinical consequences have been reported. Volumetric CT scan of liver and spleen can be used as an objective measure of the efficacy of enzyme replacement therapy during the first few months of treatment. Urine GAG assessments have not yet provided quantitative approaches to modify dosing regimens.

Unlike the use of intrathecal elaprase enzyme replacement therapy for Hunter syndrome (MPS II), the use of intrathecal administration of recombinant alpha-L-iduronidase is not available.