This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Smith-Lemli-Opitz Syndrome (SLOS) is a complex genetic disorder, associated with multiple birth defects, dysmorphic features, growth failure and mental retardation. SLOS is caused by a metabolic error in the final step of cholesterol biosynthesis. Abnormal production/function of the enzyme 7-dehydrocholesterol reductase (7DHCR) leads to a deficiency of cholesterol, and abnormal accumulation of the cholesterol precursors, 7- and 8-dehydrocholesterol (7-DHC, and 8-DHC). Both cholesterol deficiency and accumulation of 7- and 8-DHC disrupt normal embryologic development, and interfere with the normal physiological and biological functioning of multiple organ systems. The purpose of this study is to evaluate the effects of cholesterol supplementation on these abnormalities. In particular, growth and development, behavioral function, and retinal function are closely followed in SLOS patients on this protocol.Additionally, there are two areas of research focus for this protocol:1) It is now known that patients at the very mild end of the SLOS spectrum may present with autism. Whether this subset of SLOS patients will respond to cholesterol treatment and show improvement in their autistic features is an area of great interest, introducing the possibility of a potentially treatable form of autism.2) The metabolic abnormalities seen in SLOS cause severe disruption of retinal function in the rat, and documented abnormalities in retinal appearance and function have been reported in human SLOS patients. This may lead to progressive visual impairment. This protocol is the only site studying the effects of cholesterol treatment on retinal function in human patients with SLOS.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
General Clinical Research Centers Program (M01)
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Special Emphasis Panel (ZRR1-CR-9 (01))
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University of Colorado Denver
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Levenson, Amy E; Wadwa, R Paul; Shah, Amy S et al. (2017) PCSK9 Is Increased in Youth With Type 1 Diabetes. Diabetes Care 40:e85-e87
Berkowitz, Robert I; Marcus, Marsha D; Anderson, Barbara J et al. (2017) Adherence to a lifestyle program for youth with type 2 diabetes and its association with treatment outcome in the TODAY clinical trial. Pediatr Diabetes :
Arslanian, Silva; El Ghormli, Laure; Bacha, Fida et al. (2017) Adiponectin, Insulin Sensitivity, ?-Cell Function, and Racial/Ethnic Disparity in Treatment Failure Rates in TODAY. Diabetes Care 40:85-93
Gan, Ryan W; Demoruelle, M Kristen; Deane, Kevin D et al. (2017) Omega-3 fatty acids are associated with a lower prevalence of autoantibodies in shared epitope-positive subjects at risk for rheumatoid arthritis. Ann Rheum Dis 76:147-152
Nandi-Munshi, Debika; Afkarian, Maryam; Whitlock, Kathryn B et al. (2017) Vitamin D and Albuminuria in Youth with and without Type 1 Diabetes. Horm Res Paediatr 87:385-395
Liu, Edwin; Dong, Fran; Barón, Anna E et al. (2017) High Incidence of Celiac Disease in a Long-term Study of Adolescents With Susceptibility Genotypes. Gastroenterology 152:1329-1336.e1
Cree-Green, Melanie; Gupta, Abhinav; Coe, Gregory V et al. (2017) Insulin resistance in type 2 diabetes youth relates to serum free fatty acids and muscle mitochondrial dysfunction. J Diabetes Complications 31:141-148
Kriska, Andrea; El Ghormli, Laure; Copeland, Kenneth C et al. (2017) Impact of lifestyle behavior change on glycemic control in youth with type 2 diabetes. Pediatr Diabetes :
Crume, Tessa L; Hamman, Richard F; Isom, Scott et al. (2016) Factors influencing time to case registration for youth with type 1 and type 2 diabetes: SEARCH for Diabetes in Youth Study. Ann Epidemiol 26:631-7
Marcus, M D; Wilfley, D E; El Ghormli, L et al. (2016) Weight change in the management of youth-onset type 2 diabetes: the TODAY clinical trial experience. Pediatr Obes :

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