Investigation of possible desmosterolosis (desmosterol reductase deficiency) and sitosterolemia
Genetics Test Information Provides information that may help with selection of the correct test or proper submission of the test request
Testing includes desmosterol, lathosterol, campesterol, and sitosterol for the investigation of desmosterolosis and sitosterolemia.
Cholesterol plays an essential role in many cellular and developmental processes. In addition to its role as a membrane lipid, it is the precursor to numerous molecules that play an important role in cell growth and differentiation, protein glycosylation, and signaling pathways. The biosynthesis of cholesterol and its subsequent conversion to other essential compounds is complex, involving a number of intermediates and enzymes. Disorders that result from a deficiency of these enzymes lead to an accumulation of specific intermediates and inhibit the formation of important biomolecules. Clinical findings common to cholesterol biosynthesis disorders include congenital skeletal malformations, dysmorphic facial features, psychomotor retardation, and failure to thrive.
Desmosterolosis (desmosterol reductase deficiency) has a similar phenotype to Smith-Lemli-Opitz (SLO) syndrome (7-dehydrocholesterol reductase deficiency) and typically involves the central nervous system (CNS). Its biochemical marker is the elevation of desmosterol in plasma, tissue, and cultured cells.
Sitosterolemia is a rare autosomal recessive disorder caused by mutations in 2 ATP-binding cassette (ABC) transporter genes, ABCG5 and ABCG8, which abnormally enhance the absorption of plant sterols and cholesterol from the intestines. Patients often present with tendon and tuberous xanthomas as well as premature coronary artery disease. A biochemical diagnosis of sitosterolemia is made by documenting elevations of the plant sterols sitosterol and campesterol in plasma or serum.
Patients with sitosterolemia typically have campesterol values >40 mg/L and sitosterol values >80 mg/L.
A quantitative report of the patient's sterol profile and a Biochemical Genetics consultant's interpretation is provided for each specimen.
Reference ranges were derived using fasting specimens from healthy individuals. Sitosterol and campesterol values may be mildly elevated in individuals whose diets include foods with high concentrations of plant sterols, such as some vegetable oils and infant formulas.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. FitzPatrick DR, Keeling JW, Evans MJ, et al: Clinical phenotype of desmosterolosis. Am J Med Genet 1998 January 13;75(2):145-152
2. Bjorkhem I, Boberg KM, Leitersdor E: Chapter 123: Inborn Errors in Bile Acid Biosynthesis and Storage of Sterols Other than Cholesterol. In The Metabolic Basis of Inherited Disease. Eighth edition. Edited by D Valle. AL Beaudet, B Vogelstein. New York, McGraw-Hill Book Company. Available at www.ommbid.com. Accessed 02/18/2014
3. Lu K, Lee MH, Hazard S, et al: Two genes that map to the STSL locus cause sitosterolemia: genomic structure and spectrum of mutations involving sterolin-1 and sterolin-2, encoded by ABCG5 and ABCG8, respectively. Am J Hum Genet 2001 August;69(2):278-290
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5. Herman GE, Kratz L: Disorders of sterol synthesis: beyond Smith-Lemli-Optiz syndrome. Am J Med Genet C Semin Med Genet 2012;106C:301-321