Sterol and Isoprenoid Disease Research Consortium: Smith-Lemli-Opitz Syndrome (STAIR-SLOS)

Primary Outcome Measures:

• To define the rate of progression of clinical and biochemical measures in patients with Smith Lemli-Opitz syndrome receiving dietary cholesterol supplementation. [ Time Frame: Once per year at annual study visit ] [ Designated as safety issue: No ]
  This study will measure changes in whole body cholesterol pool size, 24S, cholesterol absorption and synthesis in relation with cholesterol intake and changes in clincal end-points.
  
  

Secondary Outcome Measures:

• Correlate biochemical and clinical phenotypes [ Time Frame: Once per year at annual study visit ] [ Designated as safety issue: No ]
  To correlate biochemical and clinical phenotypes in SLOS subjects given dietary cholesterol with changes in whole body cholesterol pool size, and with its major determinants (cholesterol synthesis, absorption and intake).
  
  
• Identify clinical or biochemical markers for future therapeutic trials. [ Time Frame: Once per year at annual study visit ] [ Designated as safety issue: No ]
  To identify clinical or biochemical markers that can be used as outcome measures in a future therapeutic trial.
  
  
• Identify a biochemical marker that can be used for diagnostic testing or screening. [ Time Frame: Once per year at annual study visit ] [ Designated as safety issue: No ]
  To identify a biochemical marker that can be used for diagnostic testing or screening
  
  
• Develop a registry and repository of biomaterials of SLOS patients [ Time Frame: each subject will be enrolled in the registry at the baseline/initial visit, if they choose to participate in this portion of the study ] [ Designated as safety issue: No ]
  To develop a registry of well characterized SLOS patients and to maintain a repository of biomaterials corresponding to these patients
  
  

Smith-Lemli-Opitz syndrome (SLOS) is a disorder of cholesterol synthesis, or production. It is caused by mutations in the DHCR7 gene which encodes for 7-dehydrocholesterol- Δ7-reductase, an enzyme necessary for the production of cholesterol in the body. Affected individuals exhibit multiple malformations and mental retardation. The features of SLOS are thought to be primarily related to cholesterol deficiency and accumulation of cholesterol precursors. However, the clinical phenotype is not well characterized, the biochemical pathogenesis is incompletely understood, and there is no proven therapy for this devastating condition. Thus our primary objective is to better define the clinical and biochemical phenotypes of the disease using a natural history study design. The study will contribute to creating a comprehensive SLOS patient registry, identify biomarkers that can be used for diagnostic testing, screening and outcome measures in future therapeutic trials. All patients with SLOS receive dietary cholesterol supplementation with the hope that cholesterol supplementation will improve the clinical manifestation of the disease. However, there is no evidence supporting a clinical benefit of cholesterol supplementation. Thus a secondary objective of the study is to determine if cholesterol intake correlates with changes in whole body cholesterol homeostasis and clinical end-points.