Acute myocardial infarction in a 25-year-old woman with sitosterolemia

Kawamura, Ryuki; Saiki, Hitoshi; Tada, Hayato; Hata, Akinori

doi:10.1016/j.jacl.2017.10.017

Cited by 24 publications

(20 citation statements)

References 6 publications

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“…In addition to LOF mutations, many missense mutations have also been shown to cause this situation. Moreover, we have already experienced more than 10 Japanese cases thus far 4 – 7 ) . Accordingly, we firmly believe that we have overlooked many sitosterolemic cases because serum sitosterol measurement is not available in most clinics in the world, including Japan.…”

Section: Epidemiologymentioning

confidence: 99%

“…On the other hand, sitosterolemia (OMIM #210250) is a rare, inherited, autosomal recessive disorder of lipid metabolism characterized by increased absorption and decreased biliary excretion of plant sterols and cholesterol, thus resulting in prominently elevated serum concentrations of plant sterols, such as sitosterol and campesterol 3 ) . Subjects suffering from sitosterolemia primarily present with tendinous and tuberous xanthomas and premature coronary atherosclerosis, such as FH 4 – 7 ) . LDL cholesterol levels are more variable in sitosterolemia than in other genetic hyperlipidemias but can be extremely elevated in some patients, particularly in infants; the reason for this phenomenon still remains unclear 4 ) .…”

Section: Introductionmentioning

confidence: 99%

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Sitosterolemia, Hypercholesterolemia, and Coronary Artery Disease

Tada

Nohara

Inazu

et al. 2018

J Atheroscler Thromb

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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.

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Section: Epidemiologymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sitosterolemia, Hypercholesterolemia, and Coronary Artery Disease

Tada

Nohara

Inazu

et al. 2018

J Atheroscler Thromb

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“…In summary, asymptomatic subjects (typically identified by cascade screening once a proband has been identified) can manifest no symptoms or signs to varying levels of affectations. There is no question whether affected individuals can have severe ASCVD, sometimes with fatal presentations (34)(35)(36)(37)(38), but with increased knowledge and case identification, many affected subjects have now been identified, who in the untreated state, seem to have very little evidence of ASCVD. Two new studies have now highlighted this.…”

Section: Clinical Manifestationsmentioning

confidence: 99%

Thematic Review Series: Lipid Transfer Proteins ABCG5 and ABCG8: more than a defense against xenosterols

Patel

Graf

Temel

2018

Journal of Lipid Research

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The elucidation of the molecular basis of the rare disease, sitosterolemia, has revolutionized our mechanistic understanding of how dietary sterols are excreted and how cholesterol is eliminated from the body. Two proteins, ABCG5 and ABCG8, encoded by the sitosterolemia locus, work as obligate dimers to pump sterols out of hepatocytes and enterocytes. ABCG5/ABCG8 are key in regulating whole-body sterol trafficking, by eliminating sterols via the biliary tree as well as the intestinal tract. Importantly, these transporters keep xenosterols from accumulating in the body. The sitosterolemia locus has been genetically associated with lipid levels and downstream atherosclerotic disease, as well as formation of gallstones and the risk of gallbladder cancer. While polymorphic variants raise or lower the risks of these phenotypes, loss of function of this locus leads to more dramatic phenotypes, such as premature atherosclerosis, platelet dysfunction, and thrombocytopenia, and, perhaps, increased endocrine disruption and liver dysfunction. Whether small amounts of xenosterol exposure over a lifetime cause pathology in normal humans with polymorphic variants at the sitosterolemia locus remains largely unexplored. The purpose of this review will be to summarize the current state of knowledge, but also highlight key conceptual and mechanistic issues that remain to be explored.

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Section: Introductionmentioning

confidence: 99%

“…Sitosterolemia often involves elevated levels of sitosterol and low-density lipoprotein-cholesterol (LDL-C) 4,6) . In such cases, statins sometimes insufficiently decrease LDL-C, but ezetimibe can substantially decrease LDL-C 4,6,7) . In addition, patients with sitosterolemia can have either normal, moderately elevated, or exceedingly high concentrations of TC and LDL-C. Brinton et al reported that approximately 4% of patients with LDL-C concentrations ≥ 190 mg/ dL have plasma sitosterol concentrations above the 99th percentile (≥ 8 mg/L) and approximately 0.3% have concentrations consistent with those of sitosterolemia (≥ 15 mg/L) 8) .…”

Section: Introductionmentioning

confidence: 99%

Reference Intervals of Serum Non-Cholesterol Sterols by Gender in Healthy Japanese Individuals

Yoshida

Tada

Ito³

et al. 2020

JAT

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The present study was conducted to establish a practical method for measuring non-cholesterol sterols and reference intervals of serum levels. Methods: Healthy subjects (109 men and 151 women), four patients with sitosterolemia, and 10 heterozygous mutation carriers of ABCG5/ABCG8 genes were investigated. Then, three non-cholesterol sterols (sitosterol, campesterol, and lathosterol) of fasting serum samples were measured via a practical and highly sensitive gas chromatography (GC) method with 0.2 µg/mL as the lower limit of quantification. The coefficient of variation (CV) values for within-run reproducibility were 3.06%, 1.89%, and 1.77% for lathosterol, campesterol, and sitosterol, respectively. The CV values for between-run reproducibility were 2.81%, 2.06%, and 2.10% for lathosterol, campesterol, and sitosterol, respectively. Results: The serum levels of sitosterol and campesterol were significantly higher in women than in men, whereas the serum levels of lathosterol were significantly higher in men than in women. Because of these gender difference, the determination of reference intervals of the three sterol values was performed by considering gender. The reference intervals of sitosterol, campesterol, and lathosterol were 0.99-3.88, 2.14-7.43, and 0.77-3.60 µg/mL in men and 1.03-4.45, 2.19-8.34, and 0.64-2.78 µg/mL in women, respectively. The serum levels of sitosterol and campesterol were higher in patients with sitosterolemia (94.3 47.3 and 66.3 36.6 µg/mL, respectively) than in healthy subjects. Conclusion: These results demonstrate a practical and highly sensitive GC method to measure non-cholesterol sterol levels and gender-segregated reference intervals of sitosterol, campesterol, and lathosterol in Japanese healthy subjects.

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Acute myocardial infarction in a 25-year-old woman with sitosterolemia

Cited by 24 publications

References 6 publications

Sitosterolemia, Hypercholesterolemia, and Coronary Artery Disease

Sitosterolemia, Hypercholesterolemia, and Coronary Artery Disease

Thematic Review Series: Lipid Transfer Proteins ABCG5 and ABCG8: more than a defense against xenosterols

Reference Intervals of Serum Non-Cholesterol Sterols by Gender in Healthy Japanese Individuals

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