Sitosterolemia is an autosomal recessive disorder characterized by high levels of plasma plant sterols (10-25 times higher than those of normal individuals). Additional characteristics of individuals affected with sitosterolemia are tendon and tuberous xanthomas, hemolytic episodes, arthralgias and arthritis, as well as accelerated atherosclerosis and premature coronary artery disease. The high levels of plant sterols in individuals with sitosterolemia are typically caused by increased intestinal absorption and decreased removal of plant sterols. Sitosterolemia is caused by mutations in either of the ATP-binding cassette (ABC) transporters ABCG5 or ABCG8 on chromosome 2p21 which normally function to excretion of sterols. Previously, children affected with sitosterolemia were diagnosed as having “pseudo-homozygous” familial hypercholesterolemia. Current literature indicates that all cases of sitosterolemia are caused by either mutations in ABCG8 (approximately 74% of cases) or ABCG5 (approximately 26% of cases).
Reasons for Referral:
- Identification of inherited genetic defects in ABC transporter(s) in patients with early-onset hypercholesterolemia and high levels of circulating plant sterols.
- Confirmation of a suspected diagnosis with a positive family history of early onset hypercholesterolemia and high levels of circulating plant sterols when a familial mutation is known.
- Predispositional testing for asymptomatic family members with a positive family history of hypercholesterolemia.
Sequencing for ABCG5 is carried out by amplification of all exons and intron/exon boundaries followed by bi-directional Sanger sequencing. The sensitivity of full gene sequencing is estimated to be approximately 99% for single nucleotide substitutions and small insertions/deletions. All nucleotide changes are analyzed within the context of current databases and literature to predict pathogenicity. Sitosterolemia genes (ABCG5 and ABCG8), may be sequenced individually or as a panel.
Blood: EDTA or ACD (Solution A or B):
- Adult: 5 mL
- Child: 5 mL
- Infant: 2-3 mL
DNA: 10µg at a minimum of 100ng/µL
A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES. Please include detailed clinical information, including ethnicity, clinical history, and family history.
Test Performed (Days):
Turn Around Time:
14 - 21 days
Shipment Sensitivity Requirements:
- Package and ship specimen to remain cold, but not frozen.
- Ship via overnight express, using the FedEx priority overnight label provided.
- Contact Client Services for shipping kits and instructions at (855) 535-1522.
- Berge K, et al. Accumulation of Dietary Cholesterol in Sitosterolemia Caused by Mutations in Adjacent ABC Transporters. Science 2000; 290: 1771-1775.
- Lee M, et al. Genetic basis of sitosterolemia. Curr Opin Lipidol 2001; 12(2): 141-149.
- Lu K, 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; 69: 278-290.