Neurobehavioral Phenotypes in MPS III

NCT01873911 | Completed DMC

• 2 other identifiers: 0806M35341U54NS065768
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Sanfilippo Syndrome Type A; Sanfilippo Syndrome Type B; Hurler Syndrome

Keywords

MPS IIIA; MPS IIIB; Sanfilippo syndrome type A; Sanfilippo syndrome type B; Hurler syndrome; cognitive decline; MPS IH

Outcome Measures

Primary Outcomes (1)

• Assessment of Temperament

  Using Risk Room procedures of the established "Laboratory Temperament Assessment Battery" (Lab-TAB), the investigators will measure and record each subject's startle, exploration (fear), compliance, and attachment.

  Within One Year of Enrollment

Secondary Outcomes (4)

• Quality of Life Measures

  Within One Year of Enrollment

• Event-Related Potentials Measurement

  Within One Year of Enrollment

• Magnetic Resonance Imaging Examination

  Within One Year of Enrollment

• Assessment of Cognitive Development

  Within One Year of Enrollment

Eligibility Criteria

• Age: 2 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Minnesota: lead
• Rare Diseases Clinical Research Network: collaborator
• National Center for Advancing Translational Sciences (NCATS): collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• National MPS Society: collaborator
• Shire Human Genetic Therapies, Inc.: collaborator

Study Sites (1)

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (4)

• Cleary MA, Wraith JE. Management of mucopolysaccharidosis type III. Arch Dis Child. 1993 Sep;69(3):403-6. doi: 10.1136/adc.69.3.403. No abstract available.

  PMID: 8215557 BACKGROUND

• Meyer A, Kossow K, Gal A, Muhlhausen C, Ullrich K, Braulke T, Muschol N. Scoring evaluation of the natural course of mucopolysaccharidosis type IIIA (Sanfilippo syndrome type A). Pediatrics. 2007 Nov;120(5):e1255-61. doi: 10.1542/peds.2007-0282. Epub 2007 Oct 15.

  PMID: 17938166 BACKGROUND

• Jha S, Patel R. Kluver-Bucy syndrome -- an experience with six cases. Neurol India. 2004 Sep;52(3):369-71.

  PMID: 15472430 BACKGROUND

• Angrilli A, Mauri A, Palomba D, Flor H, Birbaumer N, Sartori G, di Paola F. Startle reflex and emotion modulation impairment after a right amygdala lesion. Brain. 1996 Dec;119 ( Pt 6):1991-2000. doi: 10.1093/brain/119.6.1991.

  PMID: 9010003 BACKGROUND

Related Links

• National MPS Society

MeSH Terms

Conditions

Mucopolysaccharidosis III; Mucopolysaccharidosis I; Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Elsa G Shapiro, PhD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

• Michael Potegal, PhD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2013
• First Posted: June 10, 2013
• Study Start: December 1, 2010
• Primary Completion: July 1, 2014
• Study Completion: August 1, 2014
• Last Updated: November 1, 2019

Record last verified: 2019-10

Locations

US (1)