title: The Neurobehavioral Phenotype in Mucopolysaccharidosis Type IIIB: an Exploratory Study.
abstract: OBJECTIVE
  Our goal was to describe the neurobehavioral phenotype in mucopolysaccharidosis Type IIIB (MPS IIIB). Parents report that behavioral abnormalities are a major problem in MPS III posing serious challenges to parenting and quality-of-life for both patient and parent. Our previous research on MPS IIIA identified autistic symptoms, and a Klüver-Bucy-type syndrome as indicated by reduced startle and loss of fear associated with amygdala atrophy. We hypothesized that MPS IIIB would manifest similar attributes when assessed with the same neurobehavioral protocol.
  
  
  METHODS
  Ten patients with MPS IIIB were compared with 9 MPS IIIA patients, all older than 6. 8 younger children with Hurler syndrome (1H) were chosen as a comparison group for the Risk Room procedure; MPS IH does not directly affect social/emotional function and these younger children were closer to the developmental level of the MPS IIIB group. To examine disease severity, cognitive ability was assessed. Four evaluations were used: the Risk Room procedure (to measure social-emotional characteristics, especially fear and startle responses), the Autism Diagnostic Observation Schedule (ADOS), the Sanfilippo Behavior Rating Scale (SBRS), and amygdala brain volumes calculated from manually-traced MRI images.
  
  
  RESULTS
  The two groups are equivalent in severity and show severe cognitive impairment. On the ADOS, the MPS IIIB patients exhibited the same autistic features as IIIA. The IIIB means differed from MPS IH means on most measures. However, the IIIB group did not approach the Risk Room stranger, like the MPS IH group who kept their distance, but unlike the IIIA group who showed no fear of the stranger. On the SBRS, the MPS IIIB patients were described as more inattentive and more fearful, especially of new people than the MPS IIIA. Onsets of some disease characteristics appeared more closely spaced and slightly earlier in MPS IIIB than IIIA.
  
  
  CONCLUSIONS
  On most behavioral measures, MPS IIIB patients did not differ substantially from MPS IIIA patients over age six, demonstrating autistic features and a Klüver Bucy-like syndrome including lack of fear and poor attention. Delay in onset of behavioral symptoms was associated with later diagnosis in two patients. Lack of fear, poor attention, and autistic-like symptomatology are as characteristic of MPS IIIB as they are of MPS IIIA. A possible difference is that the some behavioral abnormalities develop more quickly in MPS IIIB, If this is so, these patients may become at risk for harm and present a challenge for parenting even earlier than do those with MPS IIIA. .In future clinical trials of new treatments, especially with respect to quality of life and patient management, improvement of these behaviors will be an essential goal. Because very young patients were not studied, prospective natural history documentation of the early development of abnormal behaviors in MPS IIIB is needed.
authors.affiliation: University of Minnesota Department of Pediatrics.
authors.forename: E
authors.initials: E
authors.lastname: Shapiro
authors.affiliation: University of Minnesota Department of Pediatrics.
authors.forename: K
authors.initials: K
authors.lastname: King
authors.affiliation: University of Minnesota Department of Pediatrics.
authors.forename: A
authors.initials: A
authors.lastname: Ahmed
authors.affiliation: University of Minnesota Division of Biostatistics.
authors.forename: K
authors.initials: K
authors.lastname: Rudser
authors.affiliation: University of Minnesota Department of Pediatrics.
authors.forename: R
authors.initials: R
authors.lastname: Rumsey
authors.affiliation: University of Minnesota Department of Pediatrics.
authors.forename: B
authors.initials: B
authors.lastname: Yund
authors.affiliation: University of Minnesota Department of Pediatrics.
authors.forename: K
authors.initials: K
authors.lastname: Delaney
authors.affiliation: University of Minnesota Department of Pediatrics.
authors.forename: I
authors.initials: I
authors.lastname: Nestrasil
authors.affiliation: University of Minnesota Department of Pediatrics.
authors.forename: C
authors.initials: C
authors.lastname: Whitley
authors.affiliation: University of Minnesota Department of Pediatrics.
authors.forename: M
authors.initials: M
authors.lastname: Potegal
keywords: Behavior phenotype; Lack of fear and autistic symptoms; Sanfilippo Syndrome, Type B