β-Sitosterolemia and Xanthomatosis

Abstract

A B S T R A C T Although the usual diet may contain 150-250 mg of plant sterols, chiefly f8-sitosterol, only trace amounts of these sterols have heretofore been found in human or animal blood and tissues. We now report elevated plant sterol levels in the blood and tissues of two sisters with extensive tendon xanthomas but normal plasma cholesterol levels. Besides. P-sitosterolemia and xanthomatosis, no other physical, mental, or biochemical abnormalities were detected.Repeatedly, the plasmas of the two sisters have contained 27.1 and 17.7 mg/100 ml of p-sitosterol, 9.7 and 8.2 mg/100 ml of campesterol, and 0.5 and 0.5 mg/100 ml of stigmasterol, respectively. These plant sterols constituted 15.6 and 11.3% of the total plasma sterols. Some 60% of the plasma f-sitosterol and campesterol was esterified; the measurable stigmasterol was entirely unesterified. The transport of the plasma P-sitosterol and campesterol was largely in low density lipoproteins (76 and 83%, respectively). High density lipoproteins carried the remainder. Plant sterols were barely detectable in the very low density lipoprotein fraction. Only trace amounts of stigmasterol could be detected in the low density and high density lipoprotein fractions. The plant sterol content of the red blood cells averaged 12-13 mg/100 ml packed cells or about 13% of the total sterols. Two tendon xanthoma biopsies with the usual high concentration of cholesterol had 36.7 and 4.0 mg of plant sterols/g dry wt, of which 25.7 and 2.9 mg were fi-sitosterol, entirely in the free form. Plant sterols were also found in adipose tissue This work was presented in part at the 65th Annual

Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion

“…S itosterolemia is a rare autosomal recessive disorder characterized by the accumulation of plant and animal sterols in blood and tissues (1,2). Affected subjects with this disorder develop large deposits of cholesterol in their skin, tendons, and coronary arteries.…”

“…The pathognomonic feature of sitosterolemia is the elevation in plasma sitosterol, the most abundant plant sterol (1). Sitosterolemic patients also accumulate other sterols in plasma including a variety of plant sterols (campesterol, stigmasterol, and avenasterol) and shellfish sterols (brassicasterol, 24-methylene cholesterol, and 22-dehydrocholesterol) (1,7).…”

“…Sitosterolemic patients also accumulate other sterols in plasma including a variety of plant sterols (campesterol, stigmasterol, and avenasterol) and shellfish sterols (brassicasterol, 24-methylene cholesterol, and 22-dehydrocholesterol) (1,7). In normal individuals these sterols are poorly absorbed and preferentially secreted into the bile (8)(9)(10).…”

Plant Sterols Cause Macrothrombocytopenia in a Mouse Model of Sitosterolemia

“…Sitosterolemia is a relatively rare autosomal recessive disorder characterized by the accumulation of plant sterols in blood and tissues. Patients frequently develop tendon and cutaneous xanthomas and, most important, are at risk of developing premature coronary atherosclerosis (11)(12)(13)(14). A number of associated features, including hemolysis, abnormal platelets, and iron deficiency, have occasionally been reported (12,15,16).…”

Hepatic ABCG5 and ABCG8 Overexpression Increases Hepatobiliary Sterol Transport but Does Not Alter Aortic Atherosclerosis in Transgenic Mice

“…The ATPbinding cassette (ABC) 1 half-transporters ABCG5 and ABCG8 (ABCG5/G8) have been recently identified as the genes defective in sitosterolemia (10 -12). The increased plasma and tissue levels of animal and plant sterols found in sitosterolemic patients have been attributed to enhanced absorption and decreased biliary excretion (1-4, 6, 8, 13-16).…”