ENZYME REPLACEMENT THERAPY IN MPS1

Objectives: To evaluate enzyme replacement therapy (ERT) in MPS1 intravenously and intrathecally.

Methods: Two patients with MPS1 one non-neurologically affected and one neurologically affected were evaluated after 30 months of treatment ERT intravenously. In one patient ERT treatment was added according to the MIRC (MPS1 Intrathecal Research Collaborative) protocol.

Results: Patient 1 is a five year old girl with Hurler's disease, diagnosed at the age of two years. Although already having central nervous system involvement with psychomotor delay, she was still an active child with good communication skills at the time of onset of treatment. Since the start of the ERT treatment there was a marked improvement of her general physical condition, with diminution of liver and spleen, less ENT infections. Echocardiography remained unchanged. She developed however brainstem compression due to meningeal thickening. Intrathecal (IT) enzyme therapy (every 4 weeks) was started. No side effects or major complications were noted during or after IT injection. Thickened CSF became progressively more fluid. A neuroradiological follow-up is still in process. The second patient is an intelligent boy with Scheie's disease. He started enzyme therapy at the age of 15 years; at that time he had severe pains in his hands with stiffness, which made writing difficult. His echocardiography showed thickening of aorta and mitral valve, both with insufficiency. Liver and spleen were enlarged. After treatment, the pains in the hands had disappeared, his echocardiography showed a less thickening of the valves, without insufficiency, liver and spleen normalized in size and mobility in his hands improved.

Conclusion: Enzyme therapy can improve quality of life in Scheie and Hurler/Scheie patients. ERT leads to a marked physical amelioration and improvement of cardiac function. Intrathecal enzyme therapy is possible and might ameliorate some of the neurological problems in children with Hurler syndrome.