Neurobehavioral Phenotypes in MPS III
Condition: Sanfilippo Syndrome Type A; Sanfilippo Syndrome Type B; Hurler Syndrome
MeSH terms: Mucopolysaccharidosis III; Mucopolysaccharidosis I; Syndrome
Study type: Observational

Summary: 
      Hypothesis #1: Factor analysis of the revised Sanfilippo Behavior Rating Scale (SBRS) will
      identify a group of externalizing behaviors and a group of Klüver-Bucy syndrome-like
      behaviors as two different factors that are at least partially independent.

      Hypothesis #2a: Children with MPS III will show more hyperlocomotion, fearlessness,
      asociality and noncompliance than children of similar cognitive ability with MPS I.

      Hypothesis #2b: These behaviors will become more frequent and/or intensify over time,
      consistent with the Cleary and Wraith (1993) model. Quantifying them will provide a more
      empirical framework for staging disease progression.

      Hypothesis #3: Brain volumetric analysis and diffusion-tensor imaging will reveal
      abnormalities of frontal and temporal lobe structures that will correlate with externalizing
      and Klüver-Bucy syndrome-like behaviors, respectively.

      Hypothesis #4. Loss of cognitive and language function as measures of neurologic decline will
      directly precede or co-vary with behavioral decline.

      The primary objective of this study is to identify the behavioral phenotype and its neural
      basis in MPS III (Sanfilippo syndrome). Is the behavioral phenotype similar to that of
      Klüver-Bucy syndrome, and is there evidence for amygdala abnormality? The secondary objective
      of this research study is to develop easily administered, sensitive and specific
      neurobehavioral and neuroimaging markers to characterize the behavioral phenotype(s) of MPS
      III; to track their progression; and to delineate their neural substrates. Such markers are
      critical for identifying the stage of disease for each patient, and to measure treatment
      outcome. Although we know that severe cognitive decline is one essential characteristic of
      MPS III, the other highly salient characteristic is a range of abnormal and disruptive
      behaviors that can include, but go well beyond, childhood noncompliance and oppositionality.
      These behaviors set Sanfilippo syndrome apart from the other MPS disorders. They cause major
      disruption in the child's familial, school, and community environments. Delineating these
      behavioral abnormalities will help in better understanding the neurological disease.
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Twenty children who have been diagnosed with MPS III type A or type B. Ten age-matched
        children (as controls) who have been diagnosed with MPS I (Hurler syndrome), who in the
        past have undergone hematopoietic cell transplantation, and who have been
        clinically-determined to have low cognitive function.
      
Keywords: MPS IIIA; MPS IIIB; Sanfilippo syndrome type A; Sanfilippo syndrome type B; Hurler syndrome; cognitive decline; MPS IH