Review of first 5 years of screening for familial hypercholesterolaemia in the Netherlands

Background Familial hypercholesterolaemia is a common lipid disorder that predisposes for premature cardiovascular disease (CVD). We set up a screening programme in the Netherlands in 1994 to: establish the feasibility of active family screening supported by DNA diagnostics; assess whether or not active identification of these patients with familial hypercholesterolaemia would lead to more cholesterol-lowering treatment; and compare diagnosis by DNA analysis with that by cholesterol measurement. Methods Both DNA analysis and measurement of cholesterol concentrations were used to screen families in which a functional mutation in the LDL-receptor gene had been detected. Findings In the first 5 years, 5442 relatives of 237 people with familial hypercholesterolaemia were screened; 2039 individuals were identified as heterozygous by LDL-receptor gene mutation analysis. At the time of examination. 667 of these adults with familial hypercholesterolaemia (39%) received some form of lipid-lowering treatment; 1 year later, this percentage had increased to 93%. In addition, laboratory analysis showed that for carriers as well as noncarriers 18% would have been misdiagnosed by cholesterol measurement alone, with sex-specific and age-specific 90th percentiles of the general Dutch population as diagnostic criteria. Interpretation Targeted family screening with DNA analysis proved to be highly effective in identifying patients with hypercholesterolaemia. Most of the identified patients sought treatment and were successfully started on cholesterol-lowering treatment to lower the risk of premature CVD. Our findings could have wider relevance for the screening of other prevalent genetic population at large.