How it’s diagnosed
Diagnosis is tricky because the disease is often confused with hypercholesterolemia. Hence it is believed that sitosterolemia is highly under diagnosed.
Normal cholesterol testing will not diagnose sitosterolemia because it cannot distinguish among the different sterols. Only specialized chromatographic analysis can isolate and measure the different sterols in the plasma. This is done with gas-chromatography or gas chromatography/mass spectrometry. Patients who have sitosterolemia can have plasma plant sterol concentrations ranging from 10-20mg/dL. Normal values of plant sterols are less than 1mg/dL.
In general plasma cholesterol concentration alone is non-diagnostic. This is because cholesterol levels can be normal in individuals with sitosterolemia and high in individuals without it, as high cholesterol can be seen in numerous other disorders (e.g. familial hypercholesterolemia).
Molecular diagnosis is now possible after the discovery of the mutated genes that cause sitosterolemia (ABCG8, ABGC5). However, it is not routinely available.
A CBC may reveal hemolytic anemia and platelet abnormalities.
Significant elevated levels of plant sterols including sitosterol, campesterol and stigmasterol can indicate Sitosterolemia. DNA mutation analysis of the ABCG5 and ABCG8 genes can be helpful in diagnostic confirmation.
If sitsoterolemia is present in the family, prenatal diagnosis for pregnancies is possible through analysis of DNA extracted from fetal cells obtained by amniocentesis (usually performed ~15-18 weeks’ gestation) or chorionic villis sampling (usually performed at ~ 10-12 weeks’ gestation).
The goal is to lower plant sterols as much as possible, control blood cholesterol levels and reduce or prevent the formation of xanthomas.
Current treatment therapies include the following:
A diet low in animal and plant sterols. Vegetable oils, margarine, nuts, seeds, avocados, and chocolate have high plant sterol levels and should be avoided. Some margarines and medications enriched with plant sterols need to be avoided if you have sitosterolemia.
Usually dietary sterol restriction alone is not sufficient. Sterol absorption inhibitor - Ezetimibe (Zetia) is currently used as the primary treatment for the disease. Zetia works to block absorption of plant sterols within the body. Dose of 10 mg daily has been show to significantly reduce blood plant sterol levels and improve hemolytic parameters. Higher doses of Zetia above 10mg do not appear to further reduce plant sterol levels. Since no studies have been published on the fetal effects of ezetimibe, it should not be used during pregnancy.
Bile acid sequestrants such as cholestryramine (8-15mg/day) may be needed if ezetimibe does not have a good response. Bile acid sequestrants work by binding sterols to bile which allows for excretion of the plant sterols.
While treatments (e.g. 10 mg Zetia) will reduce plant sterol levels, these levels may be unlikely to reach normal. When tolerated, combined treatments can decrease cholesterol and sitosterol levels by 10-50%. Hoever, some individuals respond well to medication and their levels will drop to normal.