Sitosterolemia in Iberoamerican countries: new cases and phenotype genotype analysis

Alves, Ana Catarina

http://hdl.handle.net/10400.18/8711

Use this identifier to reference this record.

Name:	Description:	Size:	Format:
EAS23_Sito_vf.pdf		1.92 MB	Adobe PDF	Download

Send Feedback

Authors

Alves, Ana Catarina

Abstract(s)

Introduction: Sitosterolemia is an autosomal recessive disorder caused by variations in ABCG5/8 genes and characterized by severely elevated plasma plant sterols, associated with xanthomas and premature cardiovascular disease. The aim of this study is to present 12 clinical cases of sitosterolemia in Iberoamerican countries. Methods: We report 11 index cases, and 4 relatives identified by cascade screening. Clinical and laboratory characteristics of individuals were determined in different countries. All individuals were sequenced for the ABCG5/8 genes in Portugal or in the country corresponding. Results: The geographical distribution of the 15 cases is as follows: seven from Spain (six compound heterozygous and one true homozygous, all in ABCG8); four from Portugal ( two true homozygous, in ABCG8, one in ABCG5 and one compound heterozygous in ABCG8); one from Argentina (true homozygous in ABCG8) and three from Uruguay (all true homozygous in ABCG8). Four index cases (~57%) and two of the relatives (40%) were diagnosed in childhood, the remaining identified as adults. Six index cases present variants in ABCG8 gene (two missense and four nonsense variants) and only one presents a homozygosity in the ABCG5 gene (frameshift variant). Conclusions: The eight variants identified in this study in ABCG8 and the one in the ABCG5 genes, indicate the genetic heterogeneity of sitosterolemia in Iberoamerican countries. The treatment for sitosterolemia is specific and completely different from the rest of hypercholesterolemias, so a correct and timely diagnosis is crucial to avoid delays in treatment that could lead to poor clinical outcomes.