Sitosterolemia

Sitosterolemia, also known as phytosterolemia, is a rare autosomal recessive lipid metabolism disorder caused by pathogenic variants in the ABCG5 or ABCG8 genes, which encode the sterolin-1 and sterolin-2 proteins respectively. These proteins normally function as a heterodimer to limit intestinal absorption and promote biliary excretion of plant sterols (phytosterols) and shellfish sterols. In sitosterolemia, the body absorbs excessive amounts of plant sterols (such as sitosterol, campesterol, and stigmasterol) and cholesterol from the diet, and fails to excrete them adequately into bile, leading to dramatically elevated plant sterol levels in the blood and tissues. The disease primarily affects the cardiovascular system, hematologic system, and skin. Key clinical features include tendon and tuberous xanthomas (cholesterol-rich deposits under the skin and in tendons), premature atherosclerosis with risk of early coronary artery disease, and hematologic abnormalities including hemolytic anemia, macrothrombocytopenia (abnormally large platelets with low platelet counts), and stomatocytosis. Some patients may present with elevated LDL cholesterol levels, which can lead to misdiagnosis as familial hypercholesterolemia, though total cholesterol may be normal or only mildly elevated in some cases. Joint symptoms, including arthritis and arthralgias, may also occur. Age of onset is variable, with xanthomas and hematologic abnormalities sometimes appearing in childhood, though some individuals remain asymptomatic until adulthood. Diagnosis is confirmed by demonstrating elevated plasma plant sterol levels and/or genetic testing. Treatment centers on dietary restriction of plant sterols and cholesterol, combined with the medication ezetimibe, which inhibits intestinal sterol absorption. Bile acid-binding resins (such as cholestyramine) may also be used. Statins alone are generally not effective. With appropriate treatment, plant sterol levels can be significantly reduced and clinical manifestations may improve or stabilize.

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