Timely diagnosis of sitosterolemia by next generation sequencing in two children with severe hypercholesterolemia

Buonuomo, Paola Sabrina; Pisciotta, Livia; Rabacchi, Claudio; Papadia, Francesco; Bruzzi, Patrizia; Tummolo, Albina; Bartuli, Andrea; Cortese, Claudio; Calandra, Sebastiano

doi:10.1016/j.atherosclerosis.2017.05.002

Cited by 24 publications

(24 citation statements)

References 38 publications

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“…Some patients present with hematologic disorders, such as stomatocytic hemolysis and macrothrombocytopenia [ 35 ]. The youngest patient diagnosed with sitosterolemia — a 2-year-old girl — had elevated LDL-C levels and tuberous and intertriginous xanthomas [ 36 ]. In another case, a 5-year-old girl died due to severe coronary three-vessel disease [ 37 ].…”

Section: Plant Sterols and Cardiovascular Riskmentioning

confidence: 99%

Phytosterols and Cardiovascular Disease

Makhmudova

Schulze

Lütjohann

et al. 2021

Curr Atheroscler Rep

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Purpose of Review Coronary heart disease is the leading cause of mortality worldwide. Elevated blood cholesterol levels are not only the major but also the best modifiable cardiovascular risk factor. Lifestyle modifications which include a healthy diet are the cornerstone of lipid-lowering therapy. So-called functional foods supplemented with plant sterols lower blood cholesterol levels by about 10–15%. Recent Findings In the recent revision of the ESC/EAS dyslipidemia guideline 2019, plant sterols are recommended for the first time as an adjunct to lifestyle modification to lower blood cholesterol levels. However, the German Cardiac Society (DGK) is more critical of food supplementation with plant sterols and calls for randomized controlled trials investigating hard cardiovascular outcomes. An increasing body of evidence suggests that plant sterols per se are atherogenic. Summary This review discusses this controversy based on findings from in vitro and in vivo studies, clinical trials, and genetic evidence.

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Section: Plant Sterols and Cardiovascular Riskmentioning

confidence: 99%

Phytosterols and Cardiovascular Disease

Makhmudova

Schulze

Lütjohann

et al. 2021

Curr Atheroscler Rep

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“…These mutations promote an increase 50 times higher in the circulating concentration of plant sterols, and are associated with early onset atherosclerosis. 33,34 It is important to point out that phytosterol supplementation is contraindicated for the rare patients that present with phytosterolemia, 4 even though the consumption of foods enriched with phytosterols is associated, in these cases, with a lower increase (about twice as low) in circulating plant sterols. 35 Another possible side effect is related to the absorption of fat-soluble vitamins and antioxidants.…”

Section: Discussionmentioning

confidence: 99%

Phytosterol supplementation in the treatment of dyslipidemia in children and adolescents: a systematic review

Mantovani

Pugliese

2021

Rev. paul. pediatr.

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Objective: To carry out a systematic review on the effects of phytosterol supplementation on the treatment of dyslipidemia in children and adolescents. Data sources: Review in the SciELO, Lilacs, Bireme, PubMed and Web of Science databases, with no time limit. Descriptors: phytosterols or plant sterols and dyslipidemias, hypercholesterolemia, cholesterol, children, adolescent, in English and Portuguese. The articles included were published in Portuguese, English or Spanish and evaluated the effect of phytosterol supplementation in pediatric patients with dyslipidemia. Documents that involved adults or animals, review papers, case studies and abstracts were excluded. Two authors performed independent extraction of articles. Of 113 abstracts, 19 were read in full and 12 were used in this manuscript. Data synthesis: Phytosterol supplementation to reduce cholesterol levels has been shown to be effective in reducing LDL-cholesterol levels by approximately 10%, with reductions above 10% in LDL-cholesterol levels observed after 8 to 12 weeks of intervention. Studies have not shown significant changes in HDL-cholesterol and triglyceride levels. Based on the absence of adverse effects, its use seems to be safe and of good tolerance in children and adolescents. Conclusions: Phytosterol supplementation seems to be of great therapeutic aid for the treatment of hypercholesterolemia in children and adolescents. Further studies assessing the long-term effect of phytosterol supplementation are necessary.

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“…Variants of ABCG5/8 are associated with sitosterolemia and higher levels of total cholesterol and triglycerides as well as lower levels of HDL-C [87] Mutation-negative patients with FH Sanger sequencing [92] Case report of FH Targeted NGS [107] Case/control study of patients with FH TaqMan genotyping [91,93,108] Case/control study of patients with FH Meta-analysis [108] PNPLA5 Individuals with extremely high and extremely low LDL-C from population-based cohorts Whole-exome sequencing Variants of PNPLA5 are associated with extremely high LDL-C levels [104] In 2019, Luis Masana and co-workers proposed a new classification of FH on behalf of the Expert Group of the Spanish Arteriosclerosis Society ( Table 2). The factors that prompted the creation of the new classification were 1) discrepancies between the clinical and genetic diagnosis of FH, when FH-associated mutations are not found in people with the clinical diagnosis of definite FH; 2) variation in the clinical signs of FH; 3) high risk of vascular complications among patients with monogenic or polygenic FH; and 4) treatment of FH confirmed by molecular genetic methods with new classes of drugs [111].…”

Section: Discussionmentioning

confidence: 99%

“…Among the patients with sitosterolemia, there are homozygotes and compound heterozygotes of substitutions Trp361X (rs137852987), Cys574Arg (rs137852988), Tyr658X (rs137852989), Arg263Gln (rs137852990), Leu596Arg, Arg412X (rs137852991), del547C, or c965-1G>C in ABCG8 or Arg408X (rs119479065), Gln251X (rs140111105), Arg446X (rs199689137), Pro231Thr, IVS10(-1)G>T (rs768019354), IVS1(-1)G>A, del1523C, IVS12(+1)G>A, or Arg419His (rs119479067) in ABCG5 [82][83][84][85][86][87][88]. It has been demonstrated that in various ethnic groups, the level of sitosterol is higher in the carriers of Gly574Arg (rs137852988) or Met429Val (rs147194762) variant [89,90].…”

Section: Abcg5 and Abcg8mentioning

confidence: 99%

Genes Potentially Associated with Familial Hypercholesterolemia

et al. 2019

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This review addresses the contribution of some genes to the phenotype of familial hypercholesterolemia. At present, it is known that the pathogenesis of this disease involves not only a pathological variant of low-density lipoprotein receptor and its ligands (apolipoprotein B, proprotein convertase subtilisin/kexin type 9 or low-density lipoprotein receptor adaptor protein 1), but also lipids, including sphingolipids, fatty acids, and sterols. The genetic cause of familial hypercholesterolemia is unknown in 20%–40% of the cases. The genes STAP1 (signal transducing adaptor family member 1), CYP7A1 (cytochrome P450 family 7 subfamily A member 1), LIPA (lipase A, lysosomal acid type), ABCG5 (ATP binding cassette subfamily G member 5), ABCG8 (ATP binding cassette subfamily G member 8), and PNPLA5 (patatin like phospholipase domain containing 5), which can cause aberrations of lipid metabolism, are being evaluated as new targets for the diagnosis and personalized management of familial hypercholesterolemia.

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Timely diagnosis of sitosterolemia by next generation sequencing in two children with severe hypercholesterolemia

Cited by 24 publications

References 38 publications

Phytosterols and Cardiovascular Disease

Phytosterols and Cardiovascular Disease

Phytosterol supplementation in the treatment of dyslipidemia in children and adolescents: a systematic review

Genes Potentially Associated with Familial Hypercholesterolemia

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