Testing toddlers for inherited heart disease

Blood test at birth could reveal genetic high cholesterol levels, potentially preventing heart problems developing in the future

UK researchers have called for familial hypercholesterolemia (FH) screening in toddlers when they have their routine immunisations. FH is a very common inherited genetic disorder affecting as many as 1 in 250 of the UK population.

Diagnosis and management

FH is the leading cause of early heart disease, but remains undiagnosed in the majority of patients, despite recent advances in genetic diagnostics. In most cases, FH is caused by mutations in one of three genes: LDLR, APOB and PCSK9.

The condition causes abnormally high cholesterol levels detectable from birth. Left untreated, patients have a 100-fold increased risk of a coronary heart disease event in early adulthood or even earlier. However, if FH is diagnosed patients can be monitored and managed with relative ease; cholesterol-lowering statins combined with a healthy lifestyle usually produces normal life expectancy.

Cascade screening

A cost-effective method of detecting FH is by testing the relatives of those diagnosed with the condition, an approach called cascade screening. This has been used in multiple parts of the UK since 2014, extending to eleven centres in England in 2015.

If FH is suspected in a patient due to high cholesterol levels or a heart attack at an early age, they are offered genetic testing. As FH is an inherited disorder, if a patient is diagnosed with the disease then their close relatives are also at risk and can be offered testing – either for the same mutation detected in the initial patient, or for high cholesterol if no mutation was detected.

Population screening

Screening whole populations for FH is a more complicated proposition than cascade screening, since there are many potentially causative mutations in the LDLR gene alone. A

New study published in the New England Journal of Medicine tested over 10,000 children around a year old for cholesterol levels and FH-linked genetic mutations. If a child had an elevated cholesterol level and either an FH mutation or a repeat elevated cholesterol level when re-tested three months later, then their parents were also tested for the mutation or cholesterol levels. For every 1000 children screened, four children and four parents were identified with FH.

Although FH is undoubtedly a genetic disease, the teams did not perform only genetic tests, because a person might carry an FH mutation without necessarily also having the raised cholesterol levels associated with an increased risk of heart disease. Similarly, cholesterol testing alone could fail to detect children with FH who would subsequently develop high cholesterol.

A better approach?

The paper proposes that a child-parent screening programme would allow FH to be picked up early in life and cardiovascular disease prevented, rather than waiting until a family member has a potentially fatal heart attack to begin screening for others at risk. Testing for FH alongside routine primary care immunisation appointments was suggested to be an ideal opportunity for such screening, with reduced costs and probable high uptake.

Lead researcher Prof David Wald told the BBC it could prevent around 600 heart attacks each year among the under-40s in England and Wales alone, observing: “It’s the only screening method that stands a reasonable chance of covering the whole population”.