Diagnosis and management of children and young people with familial hypercholesterolaemia

Abstract

Heterozygous familial hypercholesterolaemia is a common genetic condition characterised by the impaired clearance of low density lipoprotein cholesterol from the bloodstream. Incidence rates can be as high as 1/250 and those confirmed with familial hypercholesterolaemia are predisposed to progressive atherosclerosis throughout childhood, increasing their risk of premature cardiovascular disease. Early identification and initiation of risk factor management and lipid-lowering therapy are fundamental if this risk and its associated comorbidities are to be reduced and a life expectancy similar to that of the general population restored. This article discusses several aspects of familial hypercholesterolaemia including identification, diagnosis through genetic testing and treatment protocols in a tertiary cardiac centre. It aims to share key learning points with other institutions either already established in the care of paediatric patients with familial hypercholesterolaemia or those contemplating forming a service to meet the needs of this growing cohort.

Current management of children and young people with heterozygous familial hypercholesterolaemia - HEART UK statement of care

“…It is, therefore, important to start teaching children with FH about their condition and its management from 10 to 12 years of age. Better education of young FH patients should improve long-term adherence [34][35][36][37][38], and HEART UK have produced information sheets for different aged children [39].…”

Prevalence of cardiovascular events in genetically confirmed versus unconfirmed familial hypercholesterolaemia

“…In total, 110/201 or 55% of these patients were confirmed to have FH by genetic testing (57 males and 53 females); 108 were identified with heterozygous FH and two as homozygous FH, with the majority of pathogenic variants identified in the LDL receptor gene. 5 None of the patients within this paediatric cohort had cardiovascular events either at baseline or during the follow-up period. 5 Accurate diagnosis and identification of affected patients and timely implementation of preventative therapy is becoming increasingly relevant with the fast-paced development of novel therapies such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, which could have a major impact on reducing cardiovascular risk.…”

“…5 None of the patients within this paediatric cohort had cardiovascular events either at baseline or during the follow-up period. 5 Accurate diagnosis and identification of affected patients and timely implementation of preventative therapy is becoming increasingly relevant with the fast-paced development of novel therapies such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, which could have a major impact on reducing cardiovascular risk. A major challenge for clinicians is that there is no international consensus on diagnostic criteria, with widely varying models of diagnosis worldwide; 6 with some countries favouring genetic screening and others relying solely on clinical criteria if at all.…”

“…For the purposes of this analysis, paediatric patients under the age of 18 were not included as they did not have any cardiovascular events either at baseline or during the follow-up period as we previously reported. 5 All patients included in the study were screened for mutations in LDLR, APOB and PCSK9 using standard molecular genetic techniques.…”

“…3,4 Recently we reported on our paediatric FH genetic testing and follow-up service in which 201 children and young people between the ages of 1 and 18 years were genetically tested for FH between 2011 and 2016. 5 Genetic testing involved 26 index cases and 175 patients were part of the cascade testing programme. In total, 110/201 or 55% of these patients were confirmed to have FH by genetic testing (57 males and 53 females); 108 were identified with heterozygous FH and two as homozygous FH, with the majority of pathogenic variants identified in the LDL receptor gene.…”