Sitosterolemia is a rare disease with severe clinical manifestations

I. I. Pshenichnikova; I. N. Zakharova; V. V. Pupykina; S. N. Borzakova; N. D. Telezhnikova; E. S. Slastnikova; D. I. Sadykova; P. A. Vasiluev; E. Yu. Zakharova; M. V. Ezhov

doi:10.21518/ms2025-491

Sitosterolemia is a rare disease with severe clinical manifestations

https://doi.org/10.21518/ms2025-491

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Abstract

Sitosterolemia is a rare autosomal recessive dyslipidemia caused by a defect in sterol transporters, leading to excess absorption and insufficient excretion of plant sterols and cholesterol. The clinical picture ranges from xanthomatosis to early atherosclerosis and hematological disorders, often mimicking familial hypercholesterolemia. Three clinical observations are presented, illustrating the diagnostic difficulties and the effectiveness of pathogenetic therapy. Case 1: a 15-year-old female patient with severe hypercholesterolemia and negative results of testing for the classic genes of familial hypercholesterolemia; whole-genome sequencing revealed two variants in ABCG8 (c.1269G>T, p.Glu423Asp; c.322+456C>T). A diet low in phytosterols and ezetimibe ensured the achievement of target values of low-density lipoprotein cholesterol. Case 2: a 21-year-old patient with early generalized xanthomatosis and extremely high phytosterol levels; a nonsense variant of ABCG8 c.1083G>A, p.Trp361Ter was detected. Administration of ezetimibe in combination with a bile acid sequestrant resulted in a significant decrease in cholesterol. Case 3: a boy aged 2 years 7 months with multiple xanthomas; compound heterozygosity of ABCG8 (c.1715T>C, p.Leu572Pro; c.883G>A, p.Gly295Arg) was detected. Ezetimibe resulted in a significant decrease in low-density lipoprotein cholesterol and regression of xanthomas. These observations confirm the need for quantitative determination of phytosterols and extended genetic search in “atypical familial hypercholesterolemia” . Strict dietary restrictions and ezetimibe remain the basis of treatment; the effectiveness of statins is limited. Early recognition improves prognosis and reduces the risk of cardiovascular complications.

Keywords

sitosterolemia, ABCG5/ABCG8, phytosterols, ezetimibe, hypercholesterolemia in children

About the Authors

I. I. Pshenichnikova

Russian Medical Academy of Continuous Professional Education; Bashlyaeva Moscow Children’s City Clinical Hospital; Research Institute for Healthcare Organisation and Medical Management, Moscow Healthcare Department
Россия

Irina I. Pshenichnikova, Cand. Sci. (Med.), Associate Professor of the Department of Pediatrics named after Academician G.N. Speransky; Pediatrician; Specialist of the Organizational and Methodical Department of Paediatrics

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

28, Geroyev Panfilovtsev St., Moscow, 125373

9, Sharikopodshipnikovskaya St., Moscow, 115088

I. N. Zakharova

Russian Medical Academy of Continuous Professional Education
Россия

Irina N. Zakharova, Dr. Sci. (Med.), Professor, Head of the Department of Pediatrics named after G.N. Speransky

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

V. V. Pupykina

Russian Medical Academy of Continuous Professional Education
Россия

Viktoria V. Pupykina, Assistant of the Department of Pediatrics named after Academician G.N. Speransky

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

S. N. Borzakova

Svetlana N. Borzakova, Cand. Sci. (Med.), Associate Professor, Department of Paediatrics named after Academician G.N. Speransky; Paediatric Gastroenterologist; Head, Organisational- Methodological Department for Paediatrics

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

28, Geroyev Panfilovtsev St., Moscow, 125373

9, Sharikopodshipnikovskaya St., Moscow, 115088

N. D. Telezhnikova

Bashlyaeva Moscow Children’s City Clinical Hospital
Россия

Natalia D. Telezhnikova, Head of the Department of Cardiology

28, Geroyev Panfilovtsev St., Moscow, 125373

E. S. Slastnikova

Republican Center of Lipidology for Children, Children’s Republican Clinical Hospital; Kazan State Medical University
Россия

Evgeniia S. Slastnikova, Cand. Sci. (Med.), Chief Freelance Pediatric Cardiologist of Kazan, Head of the Consultative Office; Senior Lecturer of the Department of Hospital Pediatrics

140, Orenburgskiy Тract, Kazan, Republic of Tatarstan, 420138

49, Butlerov St., Kazan, Republic of Tatarstan, 420012

D. I. Sadykova

Kazan State Medical University
Россия

Dinara I. Sadykova, Corr. Member of the Academy of Sciences of the Republic of Tatarstan, Dr. Sci. (Med.), Professor, Honored Doctor of the Russian Federation, Honored Doctor of the Republic of Tatarstan, Head of the Department of Hospital Pediatrics

49, Butlerov St., Kazan, Republic of Tatarstan, 420012

P. A. Vasiluev

Medical Genetic Research Center
Россия

Peter A. Vasiluev, Geneticist, Researcher

1, Moskvorechye St., Moscow, 115478

E. Yu. Zakharova

Medical Genetic Research Center
Россия

Ekaterina Yu. Zakharova, Dr. Sci. (Med.), Head of the Laboratory of Hereditary Metabolic Diseases

1, Moskvorechye St., Moscow, 115478

M. V. Ezhov

National Medical Research Centre of Cardiology named after Academician E.I. Chazov
Россия

Marat V. Ezhov, Dr. Sci. (Med.), Professor, Chief Researcher, Laboratory of Lipid Metabolism Disorders, Myasnikov Research Institute of Clinical Cardiology

15a, Academician Chazov St., Moscow, 121552

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Review

For citations:

Pshenichnikova II, Zakharova IN, Pupykina VV, Borzakova SN, Telezhnikova ND, Slastnikova ES, Sadykova DI, Vasiluev PA, Zakharova EY, Ezhov MV. Sitosterolemia is a rare disease with severe clinical manifestations. Meditsinskiy sovet = Medical Council. 2025;(19):268–279. (In Russ.) https://doi.org/10.21518/ms2025-491

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