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.
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.
|Mauer, Michael; Glynn, Emily; Svarstad, Einar et al. (2014) Mosaicism of podocyte involvement is related to podocyte injury in females with Fabry disease. PLoS One 9:e112188|
|Rumsey, Robin K; Rudser, Kyle; Delaney, Kathleen et al. (2014) Acquired autistic behaviors in children with mucopolysaccharidosis type IIIA. J Pediatr 164:1147-1151.e1|
|Schiffmann, Raphael; Forni, Sabrina; Swift, Caren et al. (2014) Risk of death in heart disease is associated with elevated urinary globotriaosylceramide. J Am Heart Assoc 3:e000394|
|Polgreen, Lynda E; Thomas, William; Fung, Ellen et al. (2014) Low bone mineral content and challenges in interpretation of dual-energy X-ray absorptiometry in children with mucopolysaccharidosis types I, II, and VI. J Clin Densitom 17:200-6|
|Polgreen, Lynda E; Thomas, William; Orchard, Paul J et al. (2014) Effect of recombinant human growth hormone on changes in height, bone mineral density, and body composition over 1-2 years in children with Hurler or Hunter syndrome. Mol Genet Metab 111:101-6|
|Stevenson, David A; Rudser, Kyle; Kunin-Batson, Alicia et al. (2014) Biomarkers of bone remodeling in children with mucopolysaccharidosis types I, II, and VI. J Pediatr Rehabil Med 7:159-65|
|Prater, Sean N; Banugaria, Suhrad G; Morgan, Claire et al. (2014) Letter to the Editors: Concerning "CRIM-negative Pompe disease patients with satisfactory clinical outcomes on enzyme replacement therapy" by Al Khallaf et al. J Inherit Metab Dis 37:141-3|
|Schiffmann, Raphael; Mayfield, Joan; Swift, Caren et al. (2014) Quantitative neuroimaging in mucolipidosis type IV. Mol Genet Metab 111:147-51|
|Wang, Raymond Y; Braunlin, Elizabeth A; Rudser, Kyle D et al. (2014) Carotid intima-media thickness is increased in patients with treated mucopolysaccharidosis types I and II, and correlates with arterial stiffness. Mol Genet Metab 111:128-32|
|Ahmed, Alia; Whitley, Chester B; Cooksley, Renee et al. (2014) Neurocognitive and neuropsychiatric phenotypes associated with the mutation L238Q of the *-L-iduronidase gene in Hurler-Scheie syndrome. Mol Genet Metab 111:123-7|
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