The Sterol and Isoprenoid Diseases Research Consortium (STAIR) is dedicated to the investigation of rare inherited metabolic diseases that are caused by genetic defects in the biochemical pathway leading to the synthesis of sterols, isoprenoid-related molecules and metabolic products of cholesterol, such as bile acids. The objectives of the Consortium are to define the natural history and phenotypic variation of STAIR diseases, identify biomarkers that are useful as surrogate clinical outcome measures, elucidate disease pathogenesis and develop effective therapeutic interventions. The Consortium team consists of 1) clinician scientist leaders in the field, several having first discovered the geneti basis for STAIR diseases, 2) Patient Advocacy Groups to aid clinical study feasibility, recruitment and implementation and 3) the Data Management Coordinating Center (DMCC) to provide statistical support. STAIR Consortium sites are located throughout the US, Canada and the Netherlands. STAIR sites are selected to provide a wide geographic distribution and take advantage of available rare patient populations. We will accomplish STAIR objectives by performing collaborative multicenter clinical research studies and short pilot projects. Longitudinal natural history studies will focus on Sjgren-Larsson syndrome, Hyper-lgD/mevalonate kinase deficiency with periodic fevers, and newly recognized Dolichol Synthesis defects. An ongoing interventional study will examine the effect of dietary cholesterol supplementation in Smith-Lemli-Opitz syndrome. The behavioral/MRI abnormalities of subjects who are heterozygous carriers for deleterious cholesterol synthesis genes will be investigated. A pilot study will determine the optimal combination therapy for patients with Sitosterolemia. In conjunction with its clinical mission, STAIR will support the training of at least 2 new young investigators to develop the necessary laboratory and clinical skills to become leaders in rare disease research. In summary, the work of the STAIR Consortium over the next 5 years will have major impact on the understanding of the natural history, phenotypic variation and potential therapy of these rare diseases.

Public Health Relevance

The diseases studied by STAIR often go undiagnosed and have puzzling symptoms. Even after diagnosis, they have no effective therapies, leaving patients and families frustrated and disheartened. The STAIR Consortium will uncover highly relevant knowledge that is likely to advance considerably the diagnosis and therapeutic options for patients with these rare diseases.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZTR1-CI-8 (01))
Program Officer
Krotoski, Danuta
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Nebraska Medical Center
Schools of Medicine
United States
Zip Code
Freeman, Kurt A; Olufs, Erin; Tudor, Megan et al. (2016) A Pilot Study of the Association of Markers of Cholesterol Synthesis with Disturbed Sleep in Smith-Lemli-Opitz Syndrome. J Dev Behav Pediatr 37:424-30
Rizzo, William B (2016) Genetics and prospective therapeutic targets for Sjögren-Larsson Syndrome. Expert Opin Orphan Drugs 4:395-406
Merkel, Peter A; Manion, Michele; Gopal-Srivastava, Rashmi et al. (2016) The partnership of patient advocacy groups and clinical investigators in the rare diseases clinical research network. Orphanet J Rare Dis 11:66
Othman, Rgia A; Myrie, Semone B; Mymin, David et al. (2015) Ezetimibe reduces plant sterol accumulation and favorably increases platelet count in sitosterolemia. J Pediatr 166:125-31
Ajagbe, Bridget O; Othman, Rgia A; Myrie, Semone B (2015) Plant Sterols, Stanols, and Sitosterolemia. J AOAC Int 98:716-23
Jack, Loren S; Benson, Christy; Sadiq, Mohammad A et al. (2015) Segmentation of Retinal Layers in Sjögren-Larsson Syndrome. Ophthalmology 122:1730-2
Merkens, Mark J; Sinden, Nancy L; Brown, Christine D et al. (2014) Feeding impairments associated with plasma sterols in Smith-Lemli-Opitz syndrome. J Pediatr 165:836-41.e1
DeBarber, Andrea E; Luo, Jenny; Giugliani, Roberto et al. (2014) A useful multi-analyte blood test for cerebrotendinous xanthomatosis. Clin Biochem 47:860-3
DeBarber, Andrea E; Luo, Jenny; Star-Weinstock, Michal et al. (2014) A blood test for cerebrotendinous xanthomatosis with potential for disease detection in newborns. J Lipid Res 55:146-54
He, Miao; Smith, Laurie D; Chang, Richard et al. (2014) The role of sterol-C4-methyl oxidase in epidermal biology. Biochim Biophys Acta 1841:331-5

Showing the most recent 10 out of 22 publications