sitosterolemia

Sitosterolemia, also known as phytosterolemia, is a rare autosomal recessive lipid disorder characterized by the accumulation of plant sterols in the blood and tissues due to defective handling of noncholesterol sterols. People with sitosterolemia have increased intestinal absorption and decreased biliary excretion of plant sterols such as sitosterol and campesterol, leading to elevated plasma levels and incorporation into cell membranes.

The condition results from biallelic pathogenic variants in either ABCG5 or ABCG8, which encode subunits that form a heterodimer responsible for limiting dietary plant sterol absorption and promoting their excretion into bile. Loss of function causes excessive uptake of plant sterols from the gut and reduced elimination, producing a broad clinical spectrum.

Clinical features are variable. Patients may develop xanthomas, tendon xanthomas, or other lipid-rich lesions, sometimes at a young age. Premature cardiovascular disease can occur. Hematologic abnormalities such as macrothrombocytopenia or mild bleeding tendencies have been reported in some individuals. Serum cholesterol levels can be normal or only modestly elevated, and traditional lipid profiles may not explain the clinical findings.

Diagnosis is suspected when hyperlipidemia does not fit typical patterns or when plant sterol levels are disproportionately high relative to cholesterol. Measurement of plasma sitosterol and campesterol by specialized assays (GC-MS or LC-MS/MS) supports the diagnosis, which is confirmed by genetic testing for variants in ABCG5 or ABCG8.

Management centers on reducing plant sterol intake and limiting absorption. A diet restricting plant sterols and avoiding sterol-enriched foods are advised. Ezetimibe, which inhibits intestinal sterol absorption, is the main pharmacologic therapy and often lowers plant sterol levels and improves symptoms; statins may be used variably. Regular cardiovascular and hematologic monitoring is recommended. The prognosis improves with early diagnosis and appropriate treatment.