Tay-Sachs, Sandhoff, and LOTS disease is fatal genetic disorder in which harmful quantities of a fatty substance called ganglioside GM2 accumulate due to insufficient activity of an enzyme hexosaminidase. Currently, there is no treatment. Three sub-studies are proposed. Study 1 will focus on the developmental course of the spectrum of infantile Tay-Sachs disease from retrospective data. Study 2 will gather longitudinal prospective data from patients with infantile disease seen at the University of Minnesota to delineate the natural history of Tay-Sachs. Study 3 will be a longitudinal study of LOTS to understand the progression of CNS disease using quantitative methods of neuroimaging and neuropsychological measures. Objectives:
Aim 1 : Develop an index of disease progression in infantile Tay-Sachs disease through: A. First, a retrospective medical chart/record review for clinical data points. Second, participant caretakers of infants with Tay-Sachs disease will be asked to complete the University of Minnesota Natural History Study Questionnaire for Infantile Tay-Sachs Disease (MNQSTD). B. Prospective: We will collect longitudinal neuropsychological and neuroimaging data in patients with infantile Tay Sachs disease to characterize the developmental course and longitudinally examine individual growth trajectories. Predictors will include mutation type, age at diagnosis, biomarkers and surrogate markers such as MRI results.
Aim 2 : To better understand the underlying CNS structure and function abnormalities in LOTS disease and to measure change in function over time through neuroimaging and neuropsychological data. Methods: Infantile: Recruit 5 new patients the 1st year, 10 the 2nd year, and 10 the 3rd year. Each child will be seen yearly for a total of at least 3 or possibly 4 follow-up visits within the 5 year period. LOTS: Participants: Recruit 5 new patients the 1st year and 10 new patients the 2nd year. Each patient will be seen once a year. Both Infantile and LOTS: quantitative neuroimaging, biomarkers, and neuropsychological protocol will be used to collect data as well as relevant medical records.

Public Health Relevance

Currently, there is no treatment for Tay-Sachs disease, and no studies have documented the longitudinal natural history of either the early or late onset disease. The data will provide end-points for future therapies, so as to guide medical decisions about treatment and provide objective measurement of treatment outcomes. This information will help objectify disease progression to create a disease stage and severity scale to assist in diagnosis and evaluation of the outcomes of medical treatment of these children. The overall long term goal of this research is to identify brain and behavior abnormalities that can both predict course and be sensitive to change resulting from treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54NS065768-05
Application #
8545235
Study Section
Special Emphasis Panel (ZRG1-HOP-Y)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2013
Total Cost
$63,604
Indirect Cost
$20,247
Name
University of Minnesota Twin Cities
Department
Type
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Schneider, Joseph; Burmeister, Lynn A; Rudser, Kyle et al. (2016) Hypothyroidism in late-onset Pompe disease. Mol Genet Metab Rep 8:24-7
Polgreen, Lynda E; Vehe, Richard K; Rudser, Kyle et al. (2016) Elevated TNF-α is associated with pain and physical disability in mucopolysaccharidosis types I, II, and VI. Mol Genet Metab 117:427-30
Shapiro, Elsa G; Rudser, Kyle; Ahmed, Alia et al. (2016) A longitudinal study of emotional adjustment, quality of life and adaptive function in attenuated MPS II. Mol Genet Metab Rep 7:32-9
Dyke, J P; Sondhi, D; Voss, H U et al. (2016) Brain Region-Specific Degeneration with Disease Progression in Late Infantile Neuronal Ceroid Lipofuscinosis (CLN2 Disease). AJNR Am J Neuroradiol 37:1160-9
Najafian, Behzad; Tøndel, Camilla; Svarstad, Einar et al. (2016) One Year of Enzyme Replacement Therapy Reduces Globotriaosylceramide Inclusions in Podocytes in Male Adult Patients with Fabry Disease. PLoS One 11:e0152812
Shapiro, E; King, K; Ahmed, A et al. (2016) The Neurobehavioral Phenotype in Mucopolysaccharidosis Type IIIB: an Exploratory Study. Mol Genet Metab Rep 6:41-47
Rappaport, Jeff; Manthe, Rachel L; Solomon, Melani et al. (2016) A Comparative Study on the Alterations of Endocytic Pathways in Multiple Lysosomal Storage Disorders. Mol Pharm 13:357-68
Ahmed, Alia; Shapiro, Elsa; Rudser, Kyle et al. (2016) Association of somatic burden of disease with age and neuropsychological measures in attenuated mucopolysaccharidosis types I, II and VI. Mol Genet Metab Rep 7:27-31
Karimian, Zahra; Whitley, Chester B; Rudser, Kyle D et al. (2016) Delayed Infusion Reactions to Enzyme Replacement Therapies. JIMD Rep :
Kazi, Zoheb B; Prater, Sean N; Kobori, Joyce A et al. (2016) Durable and sustained immune tolerance to ERT in Pompe disease with entrenched immune responses. JCI Insight 1:

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