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 non-carriers 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 disorders in the population at large.