In neuronopathic Hunter syndrome, neurobehavioral symptoms are known to be serious but have been incompletely described. While families face significant stress stemming from this complex and far-reaching array of symptoms, neither caregiver burden nor the neurobehavioral symptoms have been measured comprehensively. We delineated these neurobehavioral characteristics and their impact on the caregiver using multiple approaches. Methods: As part of the initial phase of developing a Hunter-specific behavioral assessment tool, we used multiple methods to obtain data on patient behaviors and caregiver burden, with the intention of drafting item sets for the tool. We utilized 1) caregiver descriptions from focus groups and individual interviews, 2) observations from video-recorded play of affected children, 3) descriptions from historic chart review, 4) consultation with patient advocacy groups and international experts, 5) reports from a caregiver advisory board, and 6) literature review. Results: Neurobehavioral symptoms were diverse and categorized as focus/attention, impulsivity/heightened activity, sensation seeking, emotional/behavioral function, social interaction, and sleep. A significant reported challenge was susceptibility to misinterpretation of some behaviors as defiant or aggressive, particularly if physical. Caregiver burden involved social isolation, exhaustion, stress, and financial and vocational strain. These new descriptions will aid in developing quantitative measures of change in neurobehavioral symptoms and family burden. These descriptions will be the foundation of a neurobehavioral rating scale, which is very much needed to aid in patient management and assess interventions for individuals with neuronopathic Hunter syndrome.
Bibliographical noteFunding Information:
Eisengart: Research support from Lysogene, Sangamo and Shire/Takeda; consultant to Denali Therapeutics, Regenxbio, Sangamo, Sanofi Genzyme , and Shire/Takeda; advisory boards for Amicus, bluebird bio, and Sanofi Genzyme ; contract work for Shapiro Neuropsychology Consulting, LLC. King: Research support from Alexion Pharmaceuticals, Inc., Shire/Takeda, and Sanofi Genzyme, and contract work for Shapiro Neuropsychology Consulting, LLC. Shapiro: Partner, Shapiro Neuropsychology Consulting, LLC. Whitley: Research support from Shire /Takeda; consultant to Shire/Takeda. Muenzer: Consultant to BioMarin, Shire/Takeda, PTC Therapeutics, Green Cross, Sanofi Genzyme, Eloxx, Regenxbio, Denali Therapeutics, Sangamo and JCR Pharmaceuticals. Serves on advisory boards for BioMarin, Sanofi Genzyme, Green Cross, JCR Pharmaceuticals and Shire/Takeda. He is principal investigator for phase 1/2 and phase 2/3 trials that investigate intrathecal ERT for patients with neuronopathic Hunter syndrome, a phase 1/2 gene editing clinical trial for adults with Hunter syndrome and a phase 1/2 intravenous ERT clinical trial for MPS IIIA.
This investigator-initiated research was supported by a grant from Shire Human Genetic Therapies Inc. , Lexington, MA, a member of the Takeda group of companies through # IIR-USA-001644 , and by NIH U54NS065768 . Historic chart review and analysis was funded by NIH U54NS065768 . The Lysosomal Disease Network ( U54NS065768 ) is a part of the Rare Diseases Clinical Research Network , an initiative of the Office of Rare Diseases Research , and the National Center for Advancing Translational Sciences . This consortium is funded through a collaboration between the National Center for Advancing Translational Sciences , the National Institute of Neurological Disorders and Stroke , and the National Institute of Diabetes and Digestive and Kidney Diseases . Data curation was supported by the National Institutes of Health 's National Center for Advancing Translational Sciences , grant UL1TR002494 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health's National Center for Advancing Translational Sciences . Resources for convening the caregiver advisory board and sharing of data were provided by Denali Therapeutics (South San Francisco, CA). The advisory board was facilitated by the first author (JBE). Infrastructure support was provided by the National MPS Society , Project Alive , MPS Superhero Foundation , the University of Minnesota Department of Pediatrics , and the University of Minnesota's Center for Neurobehavioral Development . None of the funding sources had any role in study design; collection, analysis and interpretation of data; writing of the manuscript; nor the decision to submit the article for publication.
- Behavioral decline
- Hunter syndrome
- Mucopolysaccharidosis II
- Neurobehavioral symptoms
- Neuronopathic phenotype