Neurobehavioral Phenotypes in MPS III
| Status: | Completed |
|---|---|
| Conditions: | Other Indications, Metabolic |
| Therapuetic Areas: | Pharmacology / Toxicology, Other |
| Healthy: | No |
| Age Range: | 2 - 12 |
| Updated: | 2/7/2015 |
| Start Date: | December 2010 |
| End Date: | August 2014 |
| Contact: | Brenda Diethelm-Okita, MPA |
| Email: | dieth001@umn.edu |
| Phone: | 612-625-1594 |
Characterizing the Neurobehavioral Phenotype(s) in MPS III
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.
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.
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.
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.
Inclusion Criteria:
Research Subjects: Verified diagnosis of MPS IIIA or MPS IIIB (having proof of either
genetic mutation or enzymatic analysis prior to enrollment in this study); must be between
the ages of 2 and 12 years; must be able to walk.
Control group: Verified diagnosis of MPS IH; must have already undergone hematopoietic
cell transplantation in the past; must be aged between 2 and 5 years; and must be able to
walk without support.
Exclusion Criteria:
Participants will be excluded who are unable to cooperate or comply with this study's
procedures; in the opinion of the principal investigator, participants who have other
severely-limiting co-existing conditions such as severe hearing or visual impairment, will
be excluded from this study.
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