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International Journal of Molecular... Nov 2018Cholesterol is an essential component of cell barrier formation and signaling transduction involved in many essential physiologic processes. For this reason, cholesterol... (Review)
Review
Cholesterol is an essential component of cell barrier formation and signaling transduction involved in many essential physiologic processes. For this reason, cholesterol metabolism must be tightly controlled. Cell cholesterol is mainly acquired from two sources: Dietary cholesterol, which is absorbed in the intestine and, intracellularly synthesized cholesterol that is mainly synthesized in the liver. Once acquired, both are delivered to peripheral tissues in a lipoprotein dependent mechanism. Malfunctioning of cholesterol metabolism is caused by multiple hereditary diseases, including Familial Hypercholesterolemia, Sitosterolemia Type C and Niemann-Pick Type C1. Of these, familial hypercholesterolemia (FH) is a common inherited autosomal co-dominant disorder characterized by high plasma cholesterol levels. Its frequency is estimated to be 1:200 and, if untreated, increases the risk of premature cardiovascular disease. This review aims to summarize the current knowledge on cholesterol metabolism and the relation of FH to cholesterol homeostasis with special focus on the genetics, diagnosis and treatment.
Topics: Animals; Biological Transport; Cholesterol; Dietary Supplements; Genetic Testing; Humans; Hyperlipoproteinemia Type II
PubMed: 30388787
DOI: 10.3390/ijms19113426 -
Journal of Atherosclerosis and... May 2020
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Cardiometabolic Risk Factors; Cholesterol, Dietary; Gas Chromatography-Mass Spectrometry; Humans; Hypercholesterolemia; Intestinal Absorption; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Patient Care Management; Phytosterols
PubMed: 32201402
DOI: 10.5551/jat.ED126 -
Journal of Atherosclerosis and... Sep 2018Sitosterolemia is a rare inherited disease characterized by increased levels of plant sterols, such as sitosterol. The cause of this disease is ATP-binding cassette... (Review)
Review
Sitosterolemia is a rare inherited disease characterized by increased levels of plant sterols, such as sitosterol. The cause of this disease is ATP-binding cassette (ABC) subfamily G member 5 or member 8 (ABCG5 or ABCG8, respectively) gene mutations. Recent advances in genetics have revealed that the prevalence of subjects with deleterious mutations in ABCG5 and/or ABCG8 genes could be more than 1 in ~200,000 individuals among the general population. Furthermore, accumulated evidence, including infantile cases exhibiting progression/regression of systemic xanthomas associated with LDL cholesterol levels, have shown that the elevation of LDL cholesterol seems to be the major cause of development of atherosclerosis and not the elevation of sitosterol. Regarding therapies, LDL apheresis, as well as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, could be useful for sitosterolemia, in addition to ezetimibe and/or colestimide. In this study, we provide the current understanding and future perspectives of sitosterolemia, which is currently considered an extremely rare disorder but is expected to be much more prevalent in clinical settings.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Coronary Artery Disease; Heterozygote; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Mutation; Phenotype; Phytosterols; Polymorphism, Genetic; Proprotein Convertase 9; Sitosterols
PubMed: 30033951
DOI: 10.5551/jat.RV17024 -
Lipids in Health and Disease Jan 2022Sitosterolemia is a lipid disorder characterized by the accumulation of phytosterols in plasma and organs, caused by mutations in the ABCG5 and/or ABCG8 genes. The... (Review)
Review
BACKGROUND
Sitosterolemia is a lipid disorder characterized by the accumulation of phytosterols in plasma and organs, caused by mutations in the ABCG5 and/or ABCG8 genes. The disease is frequently misdiagnosed and mistreated as familial hypercholesterolemia (FH). To gain a better understanding of the disease, the current status of diagnosis and treatment of Chinese patients with sitosterolemia was reviewed and summarized.
METHOD
Literature search was performed. The clinical features and molecular characteristics of Chinese patients with sitosterolemia were analysed. Four children with sitosterolemia and the treatment experience were described.
RESULTS
Fifty-five patients with sitosterolemia have been reported in China. These patients were aged from 3 months to 67 years at diagnosis, and the median was 8 years of age. Several complications, such as xanthomas in 47 patients (85%), thrombocytopenia in 17 patients (31%), anemia in 14 patients (25%), and cardiovascular damage in 12 patients (22%), were observed. Thirty-nine patients (71%) exhibited mutations in the ABCG5 gene, 15 patients (27%) showed mutations in ABCG8, and variations in both genes occurred in one patient (2%). A patient with two clinically rare diseases, namely, sitosterolemia and glycogen storage disease type VI (GSD VI)), is reported here for the first time. The four reported patients were treated with low cholesterol and phytosterol-limited diet alone or combined with cholestyramine. Even though decreases were observed for total plasma cholesterol (TC) and low-density-lipoprotein cholesterol (LDL-C), and these levels were as low as normal in some patients, the levels of plant sterols remained above the normal range. However, TC, LDL-C and plant sterol levels remained at high levels in patients treated with a control diet control only.
CONCLUSIONS
The analysis reveals that different from Caucasians carrying mainly variations in ABCG8, most Chinese patients have mutations in the ABCG5 gene, and Arg446Ter, Gln251Ter, anArg389His might be hot-spot mutations in Chinese patients. The current survey provides clinical data to enable the development of a standardized protocol for the diagnosis and treatment of sitosterolemia in China.
Topics: ATP Binding Cassette Transporter, Subfamily G, Member 5; ATP Binding Cassette Transporter, Subfamily G, Member 8; Adolescent; Adult; Aged; Child; Child, Preschool; China; Female; Humans; Hypercholesterolemia; Infant; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Lipoproteins; Male; Middle Aged; Mutation; Phytosterols; Young Adult
PubMed: 35042526
DOI: 10.1186/s12944-021-01619-1 -
Journal of Atherosclerosis and... Aug 2021Sitosterolemia is an inherited metabolic disorder characterized by increased levels of plant sterols, such as sitosterol. This disease is caused by loss-of-function... (Review)
Review
Sitosterolemia is an inherited metabolic disorder characterized by increased levels of plant sterols, such as sitosterol. This disease is caused by loss-of-function genetic mutations in ATP-binding cassette (ABC) subfamily G member 5 or member 8 (ABCG5 or ABCG8, respectively), both of which play important roles in selective excretion of plant sterols from the liver and intestine, leading to failure to prevent absorption of food plant sterols. This disorder has been considered to be extremely rare. However, accumulated clinical data as well as genetics suggest the possibility of a much higher prevalence. Its clinical manifestations resemble those observed in patients with familial hypercholesterolemia (FH), including tendon xanthomas, hyper LDL-cholesterolemia, and premature coronary atherosclerosis. We provide an overview of this recessive genetic disease, diagnostic as well as therapeutic tips, and the latest diagnostic criteria in Japan.
Topics: Disease Management; Humans; Hypercholesterolemia; Intestinal Diseases; Japan; Lipid Metabolism, Inborn Errors; Phytosterols
PubMed: 33907061
DOI: 10.5551/jat.RV17052 -
Journal of AOAC International 2015Phytosterolemia (sitosterolemia) is a rare autosomal recessive sterol storage disease caused by mutations in either of the adenosine triphosphate (ATP) binding cassette... (Review)
Review
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.
Topics: ATP-Binding Cassette Transporters; Humans; Hypercholesterolemia; Intestinal Diseases; Lipid Metabolism, Inborn Errors; Mutation; Phytosterols; Plants
PubMed: 25941971
DOI: 10.5740/jaoacint.SGEAjagbe