CHOLESTEROL TREATMENT IN PATIENTS WITH THE SMITH-LEMLI-OPITZ SYNDROME (SLOS)

这个子项目是众多研究子项目之一

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for 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.