1 Departamento de Pediatria, HDE, CHLC, Lisboa;
2 Serviço de Cardiologia Pediátrica, HSM, CHLC, Lisboa;
3 Unidade de Nutrição e Dietética, Polo HDE, CHLC, Lisboa;
4 Unidade de Rastreio Neonatal, Metabolismo e Genética, DGH, INSA Porto;
5 Departamento de Promoção da Saúde e Prevenção de Doenças não Transmissíveis, Grupo de Investigação Cardiovascular, INSA Lisboa;
6 Unidade de Doenças Metabólicas, HDE, CHLC, Lisboa
13º Simposium Anual da Sociedade Portuguesa de Doenças Metabólicas, Évora, 16 a 18 de março de 2017 (poster em sala)
Background: Familial Hypercholesterolemia (FH) is the most common of all genetic hypercholesterolaemias with defects in LDLR, APOB and PCSK9 accounting for the majority of cases. However, there are other rare disorders like sitosterolaemia that can present the same phenotype. Both can cause premature atherosclerosis but have distinctive dietetic and therapeutic intervention.
Patient/Methods: A 5 year-old child was referred to Metabolic Clinic for xanthoma and severe hypercholesterolemia with positive family history. Molecular diagnosis was performed for LDLR, APOB, PCSK9 and ABCG8 genes. Plasma sterols analysis was also assayed.
Results: The proband was diagnosed and treated initially as FH but the lack of mutations in the LDLR, APOB (2 fragments of exons 26 and 29) and PCSK9 genes questioned this hypothesis. High plasma levels of sitosterol and the presence of phytosterols established the diagnosis of sitosterolemia, confirmed by homozygous mutation in ABCG8 gene (c.1974C>G, p.(Tyr658*)). At the same time re-sequencing of FH genes revealed a heterozygous variant in exon 26 of APOB gene (c.11477C>T, p.(Thr3826Met)), which pathogenicity was confirmed by functional studies (data not reported). Family studies revealed the same mutations in several elements. Control of LDL levels in the proband was accomplished only with combined dietary and therapeutic intervention towards both sitosterolemia and familial hypercholesterolaemia. Cardiovascular and subclinical atheroesclerosis assessment showed pre-hypertension with non-dipping pattern and intima–media thickness (IMT) in P50-75.
Comments: Correct diagnosis of the various causes of hypercholesterolaemia is important because of the different dietary and pharmacological interventions in the prevention of atherosclerosis.