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Sitosterolemia in Iberoamerican countries: New cases and phenotype genotype analysis

2023; Elsevier BV; Volume: 379; Linguagem: Inglês

10.1016/j.atherosclerosis.2023.06.953

1879-1484

Ana Catarina Alves, Joana Rita Chora, Bernardo de Paula de Miranda, Virginia Bañares, Mércia Cristina Gomes de Araújo, I. Sarasa corral, Hernan Alberto González Rojas, Ferrán Trías Vilagut, Concepció Soler, Silvia Meavilla, M. Toledo, Cristina Volpe, Ximena Reyes, Nicolás Dell’Oca, Pedro Martins, Laura Vilarinho, Agenor Dias, Pedro Valdivielso, Mafalda Bourbon,

Cholesterol and Lipid Metabolism

Background and Aims: Sitosterolemia is an autosomal recessive disorder caused by variants in ABCG5/8genes and is characterized by severely elevated plasma plant sterols, causing xanthomas and premature cardiovascular disease. The aim of this study is to present 12 clinical cases of sitosterolemia in Iberoamerican countries. Methods: We report seven index cases, and five relatives identified by cascade screening. Clinical and laboratory characteristics were determined in different countries. All individuals were sequenced for the ABCG5/8 genes either by sanger or next generation sequencing. Whenever possible sterols chromatography was performed. Results: All index children and 2 index adults presented xanthomas and children had a mean LDL of 570 mg/dL. The geographical distribution of the 12 cases is as follows: five from Spain (four compound heterozygous and one true homozygous, all in ABCG8); three from Portugal (all true homozygous, two in ABCG8 and one in ABCG5); one from Argentina (true homozygous in ABCG8) and three from Uruguay (all true homozygous in ABCG8). Six index cases present variants in ABCG8 gene (two missense and four nonsense variants) and only one presents a homozygosity in the ABCG5gene (frameshift variant). Six cases (4 index and 2 relatives) (50%) were diagnosed in childhood, the remaining were identified as adults. Conclusions: There is a genetic heterogeneity of sitosterolemia in Iberoamerican countries. The treatment for sitosterolemia is specific and completely different from the other types of hypercholesterolemia, so a correct and timely diagnosis is crucial to avoid delays in treatment that could lead to poor clinical outcomes.