The proposed study is a multi-institutional, 5-year, longitudinal study of bone disease in children with MRS I, II, and VI. The overall goal is to characterize bone disease in MRS I, II, and VI by measurements of bone architecture, density, strength, metabolism, and mobility. This will be done using the techniques of dual energy x-ray absorptiometry (DXA), peripheral quantitative computer tomography (pQCT), and serum markers of bone metabolism.
The specific aims are: 1) To characterize the bone health and bone architecture, density, strength, and mobility, and to document the natural progression of bone disease using DXA, peripheral quantitative computer tomography (pQCT), biomarkers of bone turnover, and tests of mobility. 2) In a subset of the population (height <-2 SDS) we aim to assess the efficacy of human growth hormone (hGH) on increasing growth velocity, and the impact on bone health and architecture, mobility, and neurocognitive outcomes during 2 study years. 3) To standardize measurements of DXA, pQCT, and mobility between the University of Minnesota and the University of Utah such that these measures could then be used in other network, multi-center therapeutic trials.

Public Health Relevance

This prospective study of bone disease in MRS I, II, and VI will characterize bone changes using modern methods and study the effects of growth hormone. This study will begin with Minnesota and Utah and then extend to the network with the long term goal of developing measures of bone health for therapeutic trials.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Specialized Center--Cooperative Agreements (U54)
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Special Emphasis Panel (ZRG1-HOP-Y)
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University of Minnesota Twin Cities
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Jarnes Utz, Jeanine R; Kim, Sarah; King, Kelly et al. (2017) Infantile gangliosidoses: Mapping a timeline of clinical changes. Mol Genet Metab 121:170-179
Whitley, Chester B (2017) WORLDSymposiumâ„¢ 2017 Introduction. Mol Genet Metab 120:S2-S6
Ou, Li; Przybilla, Michael J; Koniar, Brenda et al. (2017) RTB lectin-mediated delivery of lysosomal ?-l-iduronidase mitigates disease manifestations systemically including the central nervous system. Mol Genet Metab :
Solomon, Melani; Muro, Silvia (2017) Lysosomal enzyme replacement therapies: Historical development, clinical outcomes, and future perspectives. Adv Drug Deliv Rev 118:109-134
Mauer, Michael; Sokolovskiy, Alexey; Barth, Jay A et al. (2017) Reduction of podocyte globotriaosylceramide content in adult male patients with Fabry disease with amenable GLA mutations following 6 months of migalastat treatment. J Med Genet 54:781-786
Eisengart, Julie B; Jarnes, Jeanine; Ahmed, Alia et al. (2017) Long-term cognitive and somatic outcomes of enzyme replacement therapy in untransplanted Hurler syndrome. Mol Genet Metab Rep 13:64-68
Rairikar, Mugdha; Kazi, Zoheb B; Desai, Ankit et al. (2017) High dose IVIG successfully reduces high rhGAA IgG antibody titers in a CRIM-negative infantile Pompe disease patient. Mol Genet Metab 122:76-79
Ou, Li; Przybilla, Michael J; Whitley, Chester B (2017) Proteomic analysis of mucopolysaccharidosis I mouse brain with two-dimensional polyacrylamide gel electrophoresis. Mol Genet Metab 120:101-110
Rairikar, Mugdha V; Case, Laura E; Bailey, Lauren A et al. (2017) Insight into the phenotype of infants with Pompe disease identified by newborn screening with the common c.-32-13T>G ""late-onset"" GAA variant. Mol Genet Metab 122:99-107
McIntosh, Paul T; Hobson-Webb, Lisa D; Kazi, Zoheb B et al. (2017) Neuroimaging findings in infantile Pompe patients treated with enzyme replacement therapy. Mol Genet Metab :

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