Sitosterolemia Presenting as Pseudohomozygous Familial Hypercholesterolemia

Renner, Christian; Connor, William E.; Steiner, Robert D.

doi:10.3121/cmr.2016.1294

Cited by 15 publications

(9 citation statements)

References 32 publications

(52 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Current pediatric guidelines recommend primary screening at 9–11 years followed by secondary tests at 17–21 years of age [ 11 ], but these guidelines do not encompass phytosterol testing with great depth, consequently resulting in an increased risk of missing the rarer, inherited disorders. However, with increasing reports of sitosterolemia being misdiagnosed as components of familial hypercholesterolemia [ 9 , 12 ], questions are consistently being raised about the true prevalence and possible underdetection of sitosterolemia.…”

Section: Introductionmentioning

confidence: 99%

High prevalence of increased sitosterol levels in hypercholesterolemic children suggest underestimation of sitosterolemia incidence

et al. 2020

View full text Add to dashboard Cite

Background Sitosterolemia is an inherited lipid disorder which presents with elevated serum sitosterol and can result in an increased risk of premature cardiovascular disease. However, sitosterol cannot be accurately measured by routine diagnostic assays, meaning that sitosterolemia diagnosis can often be difficult, especially with many clinical features overlapping with familial hypercholesterolemia. With such complications resulting in increasing reports of misdiagnosis, the prevalence of sitosterolemia is predicted to be much higher than previously reported. Methods Gas chromatography-mass spectrometry was utilized to measure sitosterol levels of normocholesterolemic and hypercholesterolemic children. Subsequently, an epidemiologically determined cutoff level of sitosterol was calculated and applied to estimate the prevalence of children with increased sitosterol and identify potential sitosterolemia patients. Massively parallel sequencing was used to confirm the diagnosis in suspected patients. Results Samples from 109 normocholesterolemic and 220 hypercholesterolemic were tested for phytosterols. Sitosterol and campesterol levels were significantly increased in hypercholesterolemic children (mean 22.0±45.9 μmol/L for sitosterol and 26.0±32.8 μmol/L for campesterol) compared to normocholesterolemic children (mean 12.1±4.9 μmol/L for sistosterol and 14.8±6.7 μmol/L for campesterol). Via application of a cutoff of 35.9 μmol/L, the prevalence rates for increased and overtly increased sitosterol in hypercholesterolemic children were 6.4% and 1.4% respectively. Furthermore, 3 suspected sitosterolemia patients were identified, with 2 patients receiving molecular confirmation for sitosterolemia diagnosis. Conclusions Our findings reaffirm that the prevalence of sitosterolemia is probably much higher than previously reported, which also indicates the significant risk of misdiagnosis of sitosterolemia with familial hypercholesterolemia. Special lipid testing including sitosterol, especially in children with uncontrolled hypercholesterolemia, is recommended in children in order to identify potential sitosterolemia patients that would otherwise be neglected.

show abstract

Section: Introductionmentioning

confidence: 99%

High prevalence of increased sitosterol levels in hypercholesterolemic children suggest underestimation of sitosterolemia incidence

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Clinical features of STLS usually include tendinous and cutaneous xanthomas, premature coronary atherosclerosis and derived complications, and arthritis or arthralgia . These characteristics are shared with familial hypercholesterolemia (FH), so STSL may be misdiagnosed as homozygous FH, especially in pediatric patients . Unlike patients with FH, patients with STSL usually respond well to a low‐cholesterol diet and/or bile acid sequestrants such as colestimide and colestyramine .…”

Section: Introductionmentioning

confidence: 99%

Two novel variants of the ABCG5 gene cause xanthelasmas and macrothrombocytopenia: a brief review of hematologic abnormalities of sitosterolemia

Bastida

Benito

Janusz

et al. 2017

Journal of Thrombosis and Haemostasis

View full text Add to dashboard Cite

Background Sitosterolemia (STSL) is a recessive inherited disorder caused by pathogenic variants in the ABCG5 and ABCG8 genes. Increased levels of plasma plant sterols (PSs) usually result in xanthomas and premature coronary atherosclerosis, although hematologic abnormalities may occasionally be present. This clinical picture is unfamiliar to many physicians, and patients may be at high risk of misdiagnosis. Objectives To report two novel ABCG5 variants causing STSL in a Spanish patient, and review the clinical and mutational landscape of STSL. Patient/Methods A 46-year-old female was referred to us with lifelong macrothrombocytopenia. She showed familial hypercholesterolemia-related xanthomas. Molecular analysis was performed with high-throughput sequencing. Plasma PS levels were evaluated with gas-liquid chromatography. The STSL landscape was reviewed with respect to specific online databases and all reports published since 1974. Results A blood smear revealed giant platelets and stomatocytes. Novel compound heterozygous variants were detected in exons 7 (c.914C>G) and 13 (c.1890delT) of ABCG5. The patient showed an increased plasma level of sitosterol. These findings support the diagnosis of STSL. In our review, we identified only 25 unrelated STLS patients who presented with hematologic abnormalities including macrothrombocytopenia. It remains unknown why only some patients develop hematologic abnormalities. Conclusions This is the first Spanish STSL patient to be reported and molecularly characterized. The early diagnosis of STLS is strongly supported by the presence of stomatocytes in blood smears. The definitive diagnosis of STSL by measurement of serum PS levels and molecular analyses prompted the use of ezetimibe therapy.

show abstract

“…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.

View full text Add to dashboard Cite

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.

show abstract

Sitosterolemia Presenting as Pseudohomozygous Familial Hypercholesterolemia

Cited by 15 publications

References 32 publications

High prevalence of increased sitosterol levels in hypercholesterolemic children suggest underestimation of sitosterolemia incidence

High prevalence of increased sitosterol levels in hypercholesterolemic children suggest underestimation of sitosterolemia incidence

Two novel variants of the ABCG5 gene cause xanthelasmas and macrothrombocytopenia: a brief review of hematologic abnormalities of sitosterolemia

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

Contact Info

Product

Resources

About