M. Scheie: Failure of enzyme replacement therapy to prevent CNS- and spinal-lesions

Introduction: M. Hurler-Scheie (MPS I) is caused by l-iduronidase-deficiency. Enzyme replacement therapy (ERT) with recombinant l-iduronidase can improve physical capacity and reduces organomegaly. The effect on metabolism of bradytrophic connective tissue is poor. Furthermore, intravenously administered enzyme cannot cross the blood-brain barrier. Therapy of choice for the more severe Hurler- syndrome is haematopoietic stem-cell transplantation. In the milder Scheie type, neurological impairment is less severe; therefore ERT may be appropriate to treat these patients. However, information on long-term outcome in Scheie-patients undergoing ERT is scarce. We present the case of an adult female Scheie-patient receiving regular ERT for 6 years now.

Methods: We report on a 37 year old female Scheie-patient undergoing ERT with Laronidase, 100 IU/kg intravenously every week for 6 years. While non-neurological symptoms improved (except for progressive corneal clouding), she developed paraesthesias in her hands, feet and pain in her legs. SEP's (n. tibialis) were abnormal suggesting dysfunction of dorsal funiculus and lemniscus medialis respectively. A spinal MRI scan revealed spinal cord compression at the level of C1/2 due to ventral and at the level of C2/3 dorsal dural thickening by soft tissue deposits presumably due to deposition of mucopolysaccharides. Intraspinal at the level of C1/2 hyperintensities occurred, revealing cervical myelopathy. Additionally small cystic lesions were visualised in the frontal white matter associated to the corpus callosum, whereas an MRI exam performed 4 years before ERT was started, had shown small lesions periventricular and in her brain stem. Decompression of the spinal cord resulted in clinical improvement.

Conclusion: In an adult patient with M. Scheie, intravenously administered ERT failed to prevent CNS- and spinal- lesions. The clinical significance of CNS changes remains to be seen. Whether early bone marrow transplantation could have prevented CNS- and spinal- lesions is unclear.