- Top of page
- Key Points
- Genetics of Hypercholesterolaemia
- Diagnosis of Hypercholesterolaemia
- Clinical Assessment of Patients with Familial Hypercholesterolaemia
- Medical Therapy for Familial Hypercholesterolaemia
- Multiple Choice Questions
Familial hypercholesterolaemia is a disorder of low-density lipoprotein (LDL) cholesterol metabolism, which is associated with the onset of vascular changes associated with coronary heart disease in childhood. This disorder has co-dominant transmission with a prevalence of one in 500 in the general population. Cascade screening is the most effective method of identifying children. Children in the at-risk group should have their cholesterol levels checked between the age of 2 and 10 years. Children with LDL cholesterol levels ≥ 3.4 mmol/L are likely to suffer from this disorder, although at this level there is a significant false positive rate. Molecular genetic testing is available for the LDL receptor gene, APOB gene and the PCSK9 gene. This is the most specific test for familial hypercholesterolaemia but has a false negative rate of 20–50%. Once diagnosed, treatment should be considered in children with an LDL cholesterol level ≥ 4.9 mmol/L. If the child has two other risk factors or a positive family history, this threshold should be lowered to ≥4.1 mmol/L. Guidelines recommend that treatment should be commenced by the age of 10 years, although some advise waiting until menarche in females. Statin therapy is currently recommended as first line treatment. Randomised placebo trials have shown that statin therapy reduces LDL cholesterol levels by 25% and is not associated with increased risk of adverse events. These are short-term studies, and longer follow-up will be required to definitively prove efficacy and safety.