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Ana Catarina Alves1,2, Ana Medeiros1,2, Gonçalo Padeira3, Ana Cristina Ferreira3 Mafalda Bourbon1,2

1,2Unidade de I&D, Grupo de Investigação Cardiovascular, Departamento de Promoção da Saúde e Prevenção de Doenças Não Transmissíveis, Instituto Nacional de Saúde Doutor Ricardo Jorge, Lisboa, Portugal; and BioISI – Biosystems & Integrative Sciences Institute, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal;
3Unidade de Doenças Metabólicas, Área da Mulher, Criança e Adolescente, Hospital Dona Estefânia, Centro Hospitalar de Lisboa Central.

- 85th European Aterosclerosis Society Congress, Praga, 23 a 26 de Abril, 2107 (poster)

Aim: Familial Hypercholesterolaemia (FH) is the most common of all genetic hypercholesterolaemias. However there are other rare disorders presenting the same phenotype (phenocopies). Sitosterolaemia is one of those rare recessive disorders in which patients can present high levels of LDL-C but, most importantly, they present fat accumulation in tendons and arteries, leading also to increased cardiovascular risk. The defect in this case is in transporter genes responsible for the intestinal and biliary transport of plant sterols, ABCG5 or ABCG8.
Methods: A 4 years child was referred to the Portuguese FH Study, as having a clinical diagnosis of FH, with a total and LDL-C of 455 mg/dL and 391 mg/dL, and a family history of hypercholesterolaemia from her mother’s side. Molecular diagnosis was performed for LDLR, APOB, PCSK9 and ABCG8 genes. Sterols chromatography was also performed.
Results: When the screening for mutations in LDLR, APOB and PCSK9 genes turned out to be negative, the clinician asked for sterols chromatography. The high values of sitosterol changed the diagnosis of the child to sitosterolaemia and the genetic analysis revealed that the child was homozygous for a known stop mutation in ABCG8 (c.1974C>G, p.(Tyr658*)). The surprising discovery was that her mother was also homozygous for the same mutation and co-sanguinity was established. This explained the mother’s hypercholesterolaemia and why this child was wrongly diagnosed with FH.
Conclusions: This case shows that it is important to determine the genetic cause of hypercholesterolaemia in each patient in order to establish the correct treatment preventing the development of premature atherosclerosis.