Abstract
Objectives: We quantified medical signs and symptoms to construct the Physical Symptom Score (PSS) for use in research to assess somatic disease burden in mucopolysaccharidoses (MPS) to track disease and monitor treatments. We examined scoring reliability, its concurrent validity with other measures, and relationship to age in MPS type I.
Methods: Fifty-four patients with MPS I (36 with Hurler syndrome treated with hematopoietic cell transplant and 18 with attenuated MPS I treated with enzyme replacement therapy), ages 5 to 18 years, were seen longitudinally over 5 years. The summation of frequency and severity of signs of specific organ involvement, surgeries, and hydrocephalus drawn from medical histories comprise the PSS. We examined relationship to age and to daily living skills (DLS) from the Vineland Adaptive Behavior Scale and physical quality of life from the Child Health Questionnaire (CHQ) for each group.
Results: The PSS was associated with age in both groups, indicating increase in disease burden over time. The PSS was significantly negatively associated with DLS (r = −0.48) and CHQ (r = −0.55) in the attenuated MPS I but not in the Hurler group.
Conclusions: The association of somatic disease burden with physical quality of life and ability to carry out daily living skills suggests that the PSS will be useful in the measurement of disease and treatment effects in the attenuated MPS I group. Earlier treatment with transplant and differing parental expectations are possible explanations for its lack of association with other outcomes necessitating an adaptation for Hurler syndrome in the future.
Competing interests: None declared
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Acknowledgments
We are grateful to all of the families at the participating sites, as well as the principal investigators who contributed patient material and information. We are also thankful to Evelyn Redtree for her assistance with this research.
We acknowledge the contribution of data for the development of this measure from the following participating investigators and centers: Dr. Paul Harmatz at Children’s Hospital and Research Center, California, Dr. Julian Raiman at Hospital for Sick Children, Toronto, Canada and Dr. Morton Cowan at University of California, San Francisco.
The Lysosomal Disease Network (U54NS065768) supported this study through a longitudinal study called “Longitudinal Studies of Brain Structure and Function in MPS Disorders.” The Lysosomal Disease Network (U54NS065768) is a part of the National Institute of Health (NIH) Rare Diseases Clinical Research Network (RDCRN). RDCRN is an initiative of the Office of Rare Diseases Research (ORDR), NCATS (National Center for Advancing Translational Sciences), funded through a collaboration between NCATS and the National Institute of Neurological Disorders and Stroke (NINDS), and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
This project was co-funded by Genzyme-Sanofi.
This project was supported in part by the National Center for Advancing Translational Sciences, National Institutes of Health, UMN-CTSI (UL1TR000114 Dr. Rudser). The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
We are very thankful for the support provided by the Center for Neurobehavioral Development (CNBD).
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Communicated by: Frits Wijburg
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Synopsis of the Article
A reliable, validated MPS-specific Physical Symptom Score (PSS) has been developed that assesses somatic disease burden and used to evaluate treatment outcomes and disease progression for research purposes in the attenuated group of MPS I.
Compliance with Ethics Guidelines
Contributions of Individual Authors
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A. Ahmed wrote this article and contributed pertinent aspects of the planning, conduct, and reporting of the work described in the article, provided scientific expertise, and created the PSS.
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K Rudser performed the data and statistical analysis and edited the manuscript.
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A. Kunin-Batson scored and advised regarding the CHQ-PF50 and edited the manuscript.
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K Delaney managed subject recruitment, scored DLS from Vineland Adaptive Behavioral Scales (VABS), Second Edition, and provided expertise about Vineland.
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C. Whitley recruited and managed the LDN (Lysosomal Disease Network) study as a P. I. from which these subjects were selected and ensured their cooperation with study protocol.
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E. Shapiro provided scientific expertise and co-wrote the manuscript.
Corresponding and Responsible Author
Alia Ahmed, M.D.
Conflict of Interest
Elsa G. Shapiro declares that she has received funds as a consultant from Genzyme-Sanofi, BioMarin, ArmaGen, REGENXBIO, and Shire.
Kathleen Delaney declares that she has received funds as a consultant from Shire, ArmaGen, BioMarin, and REGENXBIO.
Chester B. Whitley discloses the following financial relationships:
Consultant and research support from Shire, BioMarin, Genzyme-Sanofi, and Synageva BioPharma Corp.
Alia Ahmed declares that she has no conflict of interest.
Kyle Rudser declares that he has no conflict of interest.
Alicia Kunin-Batson declares that she has no conflict of interest.
The authors confirm independence from the funders of this research; the content of the article has not been influenced by the funders.
Ethics board approval: This study was approved by the University of Minnesota Institutional Review Board: Human Subjects Committee.
Informed Consent
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.
This article does not contain any studies with animal subjects performed by any of the authors.
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Ahmed, A., Rudser, K., Kunin-Batson, A., Delaney, K., Whitley, C., Shapiro, E. (2015). Mucopolysaccharidosis (MPS) Physical Symptom Score: Development, Reliability, and Validity. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 26. JIMD Reports, vol 26. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2015_485
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DOI: https://doi.org/10.1007/8904_2015_485
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