Sitosterolemia

Louise S Merkens, Semone B Myrie, Robert D Steiner, David Mymin, Margaret P Adam, Holly H Ardinger, Roberta A Pagon, Stephanie E Wallace, Lora JH Bean, Karen Stephens, Anne Amemiya

PMID: 23556150

Abstract:

Clinical characteristics:
Sitosterolemia is characterized by:
On occasion, the abnormal hematologic findings may be the initial presentation. The phenotypic spectrum of sitosterolemia is probably not fully appreciated due to underdiagnosis and the fact that clinical findings in infants are likely to be highly dependent on diet.
Diagnosis/testing:
Increased plasma concentrations of plant sterols (especially sitosterol, campesterol, and stigmasterol) are observed once foods with plant sterols are included in the diet and have accumulated in the body. ABCG5 and ABCG8 are the only genes in which pathogenic variants are known to cause sitosterolemia. Because the proteins sterolin-1 (encoded by ABCG5) and sterolin-2 (encoded by ABCG8) form a heterodimer transporter, affected individuals have biallelic pathogenic variants in either ABCG5 or ABCG8.
Management:
Treatment of manifestations: Goals are to reduce plasma concentration of plant sterols (ideally <1 mg/dL), to control plasma concentration of cholesterol, and to prevent xanthoma formation and/or to reduce the size and number of xanthomas. Mainstay of therapy is a diet low in shellfish sterols and plant sterols (vegetable oils, margarine, nuts, seeds, avocados, and chocolate) and use of the sterol absorption inhibitor ezetimibe. In those not responsive to ezetimibe, use of cholestryramine and/or partial ileal bypass surgery is recommended. If arthritis, arthralgias, anemia, thrombocytopenia, and/or splenomegaly require treatment, the first step is management of the sitosterolemia, followed by routine symptomatic management.
Prevention of primary manifestations: See Treatment of manifestations.
Surveillance: Begin monitoring at the time of diagnosis: plasma concentrations of plant sterols (primarily beta-sitosterol and campesterol) and cholesterol; the size, number, and distribution of xanthomas; and platelet count (for thrombocytopenia), CBC (for evidence of hemolytic anemia), and liver enzymes (for elevation). In persons with long-standing untreated sitosterolemia, monitor for atherosclerosis, heart valve abnormalities, and coronary artery disease.
Agents/circumstances to avoid: Margarines and other products containing stanols (e.g., campestanol and sitostanol), which are recommended for use by persons with hypercholesterolemia, are contraindicated as they can exacerbate plant stanol accumulation.
Evaluation of relatives at risk: Early diagnosis of at-risk relatives either through measurement of plasma concentrations of plant sterols or through molecular genetic testing (if the family-specific pathogenic variants are known) allows early institution of treatment and surveillance to optimize outcome.
Pregnancy management: Since no studies have been published on the fetal effects of ezetimibe, it should not be used during pregnancy.
Genetic counseling:
Sitosterolemia is inherited in an autosomal recessive manner. Each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are possible if the pathogenic variants in the family have been identified.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP474624	Campesterol		474-62-4	Price