New insights in managing homozygous and severe heterozygous familial hypercholesterolaemia in children

This thesis delves into the management of familial hypercholesterolaemia (FH) in children, focusing on homozygous FH (HoFH) and severe heterozygous FH (HoFH). Part I explores the correlation between genotype and phenotype. It reveals that null pathogenic variants correlate with more severe phenotypes than defective variants, highlighting the importance of genetic testing for accurate diagnosis and treatment.
Part II assesses several lipid-lowering treatments (LLTs), emphasizing monoclonal antibodies targeting PCSK9 and potential therapies such as inclisiran and evinacumab. It discusses ongoing trials and future perspectives, for children with HoFH and children with HeFH and high LDL-C levels or statin intolerance. Most important, it evaluates lipoprotein apheresis as a treatment for HoFH, showing its effectiveness in lowering LDL-C levels and improving cardiovascular outcomes and provides clinical practise recommendations for integrating lipoprotein apheresis in the management of children with HoFH.
Part III addresses various aspects of FH management. It emphasizes optimal counselling for couples at risk of having a child with HoFH, investigates elevated Lp(a) levels in children with HoFH and explores the use of CTCA for assessing cardiovascular risk in HeFH and assessing efficacy of lipid-lowering treatments in HoFH.
This research contributes valuable insights into the management of HoFH and severe HeFH, highlighting the need for personalized approaches and ongoing research to improve LDL-C goal attainment and cardiovascular outcomes for affected individuals.