General description (for patients): Sitosterolemia is an inherited metabolic defect in which plant cholesterols, called sterols, are absorbed to an abnormal degree. The major one is called sitosterol from which the name is derived. High blood levels of plant sterols (blood cholesterol may be normal to high) can lead to a number of problems, including deposits (called xanthomas) in the skin as well as in tendons. Anemia and arthritis particularly in the knees and the ankles are often reported. The most serious problem is that of advanced coronary artery disease at a young age. Diets high in vegetable oils (which contain sterols) can aggravate the condition.
Medical description: Sitosterolemia is a rare recessive disorder that so far seems to have originated in a single founder leading to all cases worldwide. Excessive absorption of plant sterols leads to high plasma levels and is responsible for all the symptoms. These include the development of the tendon xanthomas in the first 10 years of life and the development of premature atherosclerosis. The latter can cause serious cardiovascular disease as early as the second decade. Sitosterolemia patients usually have normal to moderately elevated cholesterol levels and very high levels of plant sterols (sitosterol, campesterol, stigmasterol and avenosterol) in their plasma. Xanthomas may appear at any age, even in childhood. They may be present in the usual locations (e.g., tendons of the hand or the Achilles tendon) or as subcutaneous xanthomas on the buttocks. Arthritis may lead to decreased range of motion with redness, swelling and warmth of joints. High sterol levels may also cause hemolytic anemia and splenomegaly.
GENETICS: Sitosterolemia is an autosomal recessive condition due to a mutation in ABCG5 on chromosome 2 (2p21). It may work in combination with an adjacent mutation in ABCG8 in some patients. This condition occurs in the Lancaster County, PA Amish and has been reported in a Swiss patient with an identical gene profile (1720G>A in ABCG8), documenting the origin of this Amish population back to Europe more than 250 years ago.
TREATMENT: Once sitosterolemia is diagnosed, a diet low in plant sterols should be recommended, including nuts, seeds, olives, avocados, vegetable oils, shortening, margarine and chocolate (high in plant sterols). If the dietary treatment alone is insufficient, bile acid-binding resins (e.g., Colestipol, cholestyramine) or competitive inhibitory agents (e.g., Sitostanol) could be considered. In October 2002, ezetimibe, a new cholesterol absorption inhibitor received US Food and Drug Administration (FDA) approval for use in sitosterolemia.
PROGNOSIS: The prognosis for most patients with sitosterolemia is unclear, given the extreme rarity of the disease. Early diagnosis and treatment correlate with a better outcome. Left untreated, sitosterolemia has significant morbidity and increased risk of early mortality from complications of atherosclerosis. The availability of ezetimibe may dramatically improve the prognosis.
ANCILLARY TREATMENTS AND SUPPORT: Dietary control.
SPECIALISTS AND SPECIALITY CENTERS: Nutritionist, cardiologist.
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