Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phytosterolaemia (beta-sitosterolaemia), a rare, autosomal recessive disorder, has not hitherto been reported in Southern Africa. We report four new homozygous patients, from three unrelated families with significant beta-sitosterolaemia (6.6-11.3%), campesterolaemia (2.2-4.6%) and clearly detectable, though unquantified, levels of cholestanol. Three of the four patients had characteristic cutaneous and tendinous xanthomas within the first decade of life. The fourth patient, a 5 year old, was free of xanthomas despite persistently elevated concentrations of plant sterols in her plasma. All our patients were female bringing the male:female ratio in reported cases to 8:23. All were at or below the 50th percentile for height and weight, and presented at some stage with borderline, hypochromic anaemia associated with red cell abnormalities and thrombocytopaenia. The oldest patient showed suggestive clinical evidence of atherosclerosis affecting her aorta, ileofemoral bifurcation and possibly coronary arteries. All homozygotes responded to a diet restricted in phytosterols and the administration of cholestyramine with falls in plasma sterols of up to 68%. The recent discovery of a possible inherited defect in the synthesis of HMG CoA reductase in patients with phytosterolaemia makes this disorder a model system for studying the biological role of this enzyme in regulating the absorption and clearance of sterols other than cholesterol, and the factors governing the sterol composition of cell membranes.
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PMID:Phytosterolaemia in three unrelated South African families. 797 27

Phytosterolaemia (sitosterolaemia) is a very rare inherited sterol storage disease characterized by tendon and tuberous xanthomas and by a predisposition to atherosclerosis. We here describe the first Scandinavian case. The 14-year-old female patient was found to have markedly elevated circulating levels of plant sterols (sitosterol, sitostanol, campesterol, stigmasterol), and the levels of these sterols were 20-50 times higher than in her healthy sister and heterozygous parents. In addition to the usual serum plant sterols we found a new major sterol in the patient tentatively identified as episterol or fecosterol (24-methyliden-cholest-7 (or 8)-en-3 beta-ol). A newly developed method based on the use of deuterium labelled cholesterol and plant sterols was used to measure sterol absorption in the patient and her relatives. Absorption of sitosterol averaged 20% in the patient and ranged from 4 to 8% in the relatives. Absorption of campesterol averaged 31% in the patient and ranged from 15 to 18% in her relatives. Absorption of cholesterol averaged 63% in the patient and ranged from 35 to 45% in the relatives. Cholesterol synthesis appeared to be reduced in the patient and was 46-52% of that of her relatives.
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PMID:Phytosterolaemia in a Norwegian family: diagnosis and characterization of the first Scandinavian case. 876 27

Phytosterolaemia (sitosterolaemia) is a very rare inherited sterol storage disease characterized by tendon and tuberous xanthomas and by a strong predisposition to premature coronary atherosclerosis. In addition to increased or normal serum cholesterol, patients are found to have markedly elevated concentrations of the phytosterols sitosterol and campesterol. These sterols accumulate in all tissues, except the brain. Increased intestinal absorption of plant sterols, impaired biliary excretion, and decreased cholesterol synthesis are suggested as causes for this disease. However, the primary defect has not yet been identified. As well as dietary restrictions of cholesterol and plant sterols, therapeutic approaches based on interruption of the enterohepatic circulation of bile acids by administration of bile acid-binding resins or ileal bypass surgery have been recommended as therapeutic approaches to reduce all serum sterols. Administration of sitostanol, a nonabsorbable saturated plant sterol, showed a significant reduction of serum plant sterols and cholesterol in two patients with phytosterolaemia, presumably by competitive inhibition of sterol absorption.
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PMID:Phytosterolaemia: diagnosis, characterization and therapeutical approaches. 924 Jun 21

Phytosterolemia is an autosomal recessive disorder characterized by the excessive absorption, reduced excretion, and consequent high tissue and plasma levels of plant sterols, by the presence of tendon xanthomas, and by premature atherosclerosis. Low HMG-CoA reductase (HRase) activity and mass have been reported in liver and mononuclear leucocytes and low mRNA levels in liver from phytosterolemic subjects. These results led to the proposal that the primary defect in this condition involves the HRase gene locus. We examined this hypothesis in phytosterolemic subjects and heterozygous parents from four unrelated families. A variable number tandem repeat (VNTR) polymorphism of the HRase gene in the three informative families and a ScrFI restriction fragment length polymorphism (RFLP) within intron 2 of the gene in one of these families, segregated independently of the disease phenotype. Biological parentage was confirmed in the family in whom both polymorphisms failed to segregate with the disorder. These results conclusively exclude the HRase gene locus as the site of the primary defect in phytosterolemia. The study was extended by examining plasma levels of mevalonic acid and lathosterol, both markers of cholesterol biosynthesis, in response to cholestyramine, a bile acid sequestrant that is known to up-regulate HRase. Oral administration of cholestyramine resulted in a substantial (7.7-fold) increase in mevaIonic acid levels in two phytosterolemic subjects, compared with a 2.2-fold rise in their obligate heterozygote parents and a 2.3-fold increase in three healthy control subjects. The lathosterol/cholesterol (L/C) ratio showed a quantitatively similar response. Baseline levels of mevalonate and the L/C ratio were low in the phytosterolemic patients in conformity with reports of reduced cholesterol biosynthesis and HRase activity in this disorder. These functional data provide support for the concept that the primary defect in phytosterolemia does not affect a trans gene locus responsible for the constitutive expression or regulation of HMG-CoA reductase.
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PMID:HMG-CoA reductase is not the site of the primary defect in phytosterolemia. 961 Jul 72

Phytosterolemia (sitosterolemia) is a rare autosomal recessive sterol storage disease caused by mutations in either of the adenosine triphosphate (ATP) binding cassette transporter genes; (ABC) G5 or ABCG8, leading to impaired elimination of plant sterols and stanols, with their increased accumulation in the blood and tissues. Thus the disease is characterized by substantially elevated serum plant sterols and stanols, with moderate to high plasma cholesterol levels, and increased risk of premature atherosclerosis. Hematologic abnormalities including macrothrombocytopenia, stomatocytosis and hemolysis are frequently observed in sitosterolemia patients. Currently, ezetimibe, a sterol absorption inhibitor, is used as the routine treatment for sitosterolemia, with reported improvement in plant sterol levels and hemolytic parameters. This review summarizes the research related to the health impact of plant sterols and stanols on sitosterolemia.
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PMID:Plant Sterols, Stanols, and Sitosterolemia. 2594 71