Familial hypercholesterolaemia screening

Familial hypercholesterolaemia (FH) is an autosomal dominant disorder with an incidence of 1 in 300. Mutations are often found in the low-density lipoprotein receptor (LDLR) gene, the apolipoprotein B (APOB) gene, or the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene. Most individuals are unaware of their condition; a recent publication estimated that only 10% of affected individuals are diagnosed and treated.

Without treatment, patients are at very high risk of developing early cardiovascular disease. Vascular disease progresses silently, and FH is often only recognised after a first potentially fatal myocardial infarction or stroke, occurring at a very young age (before 40).
Patients with FH have a 100-fold increased risk of dying from coronary heart disease between the ages of 20 and 40. However, if treatment is started in childhood, cardiovascular disease can be prevented. The treatment available for children is mainly based on statins, which are approved for use from the age of 6 and are safe and generally well tolerated.

It is essential to identify affected individuals as early as possible and to start treatment quickly. Hypercholesterolaemia can be easily detected by a blood test. The diagnosis of FH in children is based on high LDL cholesterol levels in the blood, a family history of early cardiovascular disease and genetic testing. FH is therefore an ideal candidate for a screening programme.

Since it is inherited in an autosomal dominant manner, there is usually a parent who is also affected (who may be unaware that they have the condition). We will implement reverse cascade screening: if a child is diagnosed with FH, we will test their parents and siblings to identify other affected family members. The latter will receive medical follow-up and treatment.

Cholesterol levels stabilise after the age of 1. We recommend screening between 18 and 24 months, when the child is still being regularly monitored by their paediatrician or family doctor. Families receiving the screening invitation will have the opportunity to discuss it with their GP. The aim is to detect affected children at an early stage, but also to identify parents who are not yet aware of their condition, in order to prevent a first cardiovascular event in young parents.

A pilot study conducted in Luxembourg City (EARLIE) showed that capillary lipid profiling is a reliable way of identifying patients at risk of FH. If the initial lipid profile shows high total cholesterol (TC) (> 230 mg/dl) and/or high LDL (> 160 mg/dl), the family will be referred to the CHL's paediatric lipid centre for follow-up. If lipid values are slightly elevated (TC between 100 and 230 mg/dl and/or LDL between 130 and 160 mg/dl), additional testing will be recommended by the attending physician. If lipid levels are normal (TC < 200 mg/dl and LDL < 130 mg/dl), this reassuring result will be communicated to the family.