Sitosterolemia in Iberoamerican countries: 16 new cases and phenotype genotype analysis.

作者：A. C. Alves, J. Chora, Beatriz Miranda, A. Medeiros, R. Graça, V. Bañares, M. Araujo, F. Vilagut, Cristina Soler, S. Meavilla, M. B. Toledo, C. Volpe, X. Reyes, Nicolas Delloca, P. Martins, Diana Marado, Laura Vilarinho, Aureliano Dias, A. C. Ferreira, Gonçalo Padeira, M. Casañas, Diana Alegre-González, J. Lozano, P. Aguiar, F. Gonçalves, Ander Ernaga, M. Apellániz-Ruiz, R. Rubi, Nahún Muñoz Figueroa, Norma Alejandra Vasquez, P. Valdivielso, M. Bourbon · 发表于：Journal of Clinical Lipidology · 年份：2025 · DOI：10.1016/j.jacl.2025.08.020 · 被引用次数：4 · 研究领域：Medicine

BACKGROUND Sitosterolemia is a rare autosomal recessive lipid disorder caused by biallelic pathogenic variants in ABCG5 or ABCG8 genes. It is characterized by elevated plasma plant sterol concentrations, xanthomas, and an increased risk of premature cardiovascular disease. As happens with familial hypercholesterolemia (FH), sitosterolemia is subdiagnosed and is frequently confounded with FH, resulting in inappropriate management. This study aims to describe newly identified cases across Iberoamerican countries and to highlight the need for improved diagnostic strategies. METHODS We report 16 cases of molecularly confirmed sitosterolemia from 5 Iberoamerican countries (Argentina, Mexico, Portugal, Spain, and Uruguay), including 12 index cases and 4 relatives identified by cascade screening. Clinical, biochemical, and molecular data were collected and analyzed. β-sitosterol levels were measured when possible, and variant classification followed American College of Medical Genetics and Genomics (ACMG) guidelines with disease-specific adaptations. RESULTS Fifteen individuals had biallelic variants in ABCG8 and 1 had a homozygous frameshift variant in ABCG5. Ten distinct ABCG8 variants were identified, including 7 nonsense and 3 missense variants. Xanthomas were observed in 56% of cases. Most cases were initially diagnosed as FH, with a diagnostic delay of up to 30 years. Treatment with ezetimibe, alone or combined with statins, led to biochemical and clinical improvement, inc...