PP03.12 – 2645: Identification of early clinical markers for the prediction of neurological involvement in patients with Hunter syndrome: Data from the Hunter Outcome Survey (HOS)

Abstract

Objective Hunter syndrome (mucopolysaccharidosis type II, MPS II, OMIM 30990) is a rare, progressive, X-linked disorder caused by a deficiency in the lysosomal enzyme iduronate-2-sulfatase. All patients present with somatic manifestations of the disease, and the most severely affected individuals also display progressive neurological involvement leading to cognitive impairment. The aim of this analysis was to identify early clinical markers that may predict the development of central nervous system involvement in patients with Hunter syndrome. Methods As of January 2014, data on the prevalence of disease manifestations reported before the age of 2 years were available for 435 patients enrolled in the Hunter Outcome Survey (a Shire-sponsored, multi-national, observational registry). Patients (aged ≥5 years at last assessment) were categorized into severe and non-severe disease groups based on their most recent classification by clinical impression. Clinical markers were compared in the two groups. Results The median ages at onset of signs and symptoms in the severe (n=205) and non-severe (n=230) disease groups were 3.1 and 4.0 years, respectively. In the severe disease group, the proportion of patients experiencing regression in developmental milestones was larger and the prevalence of some signs and symptoms reported before 2 years of age was higher than in the non-severe group. These included neurological manifestations such as cognitive problems (33% versus 4%, respectively), behavioural problems (17%, 2%), hyperactivity (18%, 2%) and fine motor skills impairment (18%, 9%), and somatic manifestations such as coarse facial features (50%, 39%), upper airway infections (32%, 20%), increased upper airway sounds (13%, 7%), rhinor-rhoea (24%, 13%), nasal obstruction (19%, 8%), diarrhoea (18%, 10%) and delayed dentition (13%, 5%). Conclusion Awareness of the clinical markers identified here may aid neurologists with early recognition of patients with Hunter syndrome who are likely to develop neurological involvement.