OBJECTIVES: The purpose of this study was to evaluate the cost effectiveness (cost utility) of idursulfase (Elaprase) treatment of people with Mucopolysaccharidosis II in the UK. METHODS: Mucopolysaccharidosis II (MPS II; also referred to as Hunter's Syndrome) is an ultra-orphan lysosomal storage disorder that reveals itself around the age of 3 years and leads to disabling clinical manifestations and early death. Enzyme replacement therapy (ERT) using idursulfase was compared to palliative care, as no other pharmacological treatment is available. A cost utility cohort model was developed using utility assumptions drawn from the literature. Data were derived where possible from the idursulfase pivotal trial, from published literature and from historical records of the UK MPS Society. Where data was not available, reasonable assumptions were made, with varying scenarios employed as sensitivity analyses. Current palliative care employs physiotherapy, oxygen and care by parents, but varies by severity of the disease. This lack of consistent approach to palliative care meant that no direct cost could be assigned. Due to little clinical experience, only three disease states were considered: idursulfase-treated, palliative care, and death. The maximum time horizon was 15 years to account for the chronic nature of the disease and to encompass the benefits of idursulfase treatment, which are be expected to change the course of the disease over the long term. Costs were calculated from UK 2007 prices. Costs and benefits were discounted annually at 3.5%. RESULTS: The model showed a discounted incremental cost effectiveness ratio (ICER) over palliative care of GBP564,692 per quality adjusted life year (QALY). Sensitivity analyses showed that the two key drivers of the ICER are quality of life and mortality. CONCLUSION: Although high, the ICER for MPS II is consistent with other orphan diseases treated with ERT, such as Gaucher's and Fabry's diseases.