Neurobehavioral Phenotypes in MPS III

Like some other mucopolysaccharidosis (MPS) syndromes, MPS III (Sanfilippo syndrome) is characterized by a severe cognitive decline ending in dementia and death. Unlike other MPS syndromes, earlier-stage MPS III is also associated with a range of abnormal and disruptive behaviors that can include, but go well beyond, childhood noncompliance and oppositionality. These behaviors, which cause major disruption in the child's familial, school, and community environments, set MPS III apart from the other MPS disorders. These behaviors may also indicate the identity of the neural pathways affected in this disease; their sequence of onsets may indicate the order in which these pathways are affected. We propose to define and categorize the behavioral profile(s) or phenotype(s) of MPS III and correlate them with clinical quantitative neuroimaging in order to understand the neural bases of the disease. In addition, we will use these results to develop a set of sensitive and specific measures that can be easily administered by health care professionals to help monitor the disease and the efficacy of future treatments.