Mucopolysaccharidosis Type IIIA presents as a variant of Klüver-Bucy syndrome

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Mucopolysaccharidosis Type IIIA (MPS IIIA) is a neurodegenerative disease with behavioral symptoms unique among the mucopolysaccharidoses. Children with MPS IIIA reportedly mouth things, explore novel environments almost continuously, disregard danger, and empathize/socialize and comply less with parents. These characteristics resemble Klüver-Bucy syndrome (K-Bs). To test the K-Bs hypothesis, 30 children with MPS IIIA were compared to 8 "posttransplant" mucopolysaccharidosis Type IH patients in an experimental "risk room." The room contained attractive and mildly frightening objects, exposure to a 92-dB startle noise triggered by contact with an attractive toy, mother's return after a brief absence, and compliance with her cleanup directive. Children with MPS IIIA: (a) left mother sooner, (b) wandered more, (c) were more likely to approach frightening objects, (d) were less likely to respond to loud noise with whole body startle, (e) were less likely to avoid the toy associated with the startle noise, (f) interacted less with mother upon her return, and (g) complied less with her cleanup command. K-Bs is associated with loss of amygdala function. Brain magnetic resonance imaging (MRI) of a subset of the children with MPS IIIA showed volume loss that was greater in the amygdala than in the hippocampus; only amygdala loss correlated with reduced fearfulness. MPS IIIA may be the first identified pediatric disease presenting systematically as a K-Bs variant. If validated by further studies, the K-Bs hypothesis of MPS IIIA would provide important clinical and theoretical information for the guidance of families as well as markers for natural disease progression and treatment effects.

Original languageEnglish (US)
Pages (from-to)608-616
Number of pages9
JournalJournal of Clinical and Experimental Neuropsychology
Issue number6
StatePublished - Jul 1 2013

Bibliographical note

Funding Information:
We thank Kendra Bjoraker for her observations and interpretations of the behaviors of children with mucopolysaccharidosis Type IIIA (MPS IIIA. Kevin Donley and Neha Rajagopal assisted at early stages of this project. Kent Osman and Joel Westacott contributed to the instrumentation of the startle apparatus. Testing was carried out in the University of Minnesota’s Center for Neurobehavioral Development (CNBD), and we thank the staff of the CNBD for their considerable assistance. We also thank the MPS Society for their help in disseminating information about the study and recruiting families. Finally, we appreciate the participation of the children and their parents without whom this study would not have been possible. This study was supported by NIH (National Institutes of Health) Grant U54NS065768 and a grant from Shire HGT. The magnetic resonance imaging (MRI), cognitive, and auditory brainstem response (ABR) data were contributed by Shire HGT for the children in the study “A 12-month Longitudinal, Prospective, Observational, Natural History Study of Patients with Sanfilippo Syndrome Type A (MPS IIIA).” Address correspondence to: Michael Potegal, MMC 486, 420 Delaware St SE, Minneapolis, MN 55455, USA (E-mail:


  • Amygdala
  • Fear conditioning
  • Orality
  • Sanfilippo syndrome
  • Startle


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