Results from a family and DNA based active identification programme for familial hypercholesterolaemia

Heterozygous familial hypercholesterolaemia (FH) is a common inborn error of lipoprotein metabolism, which strongly predisposes for coronary artery disease and premature cardiac death.1 In 1994, a family based active identification programme for FH was implemented in the Netherlands.2 It is based on DNA diagnosis of the LDL-receptor gene mutation, which enables us to search selectively for patients in a high risk population. The programme initially targets first and second degree relatives of FH probands (diagnosed at Lipid Research Clinics throughout the country) and extends further into the family only when new patients are identified. The programme aims to identify mutation carriers and to refer them to Lipid Research Clinics for extensive individual risk assessment and, if necessary, treatment. As no carefully collected data are available for cholesterol levels among the general population of LDL-receptor gene mutation carriers, the large majority of whom are asymptomatic, we studied the prevalence of hypercholesterolaemia among screenees with a proved LDL-receptor gene mutation. Between 1994 and 1998 2814 adults were screened. The estimated response rate was constant over the years at 90%.3 4 For reasons of comparison with available population data for total serum cholesterol levels,5 we selected those who were between 20 and 60 years of age (1856 screenees). Depending on the available funds in the screening programme, which were lacking in certain periods, single cholesterol measurements were taken at the time of screening. Therefore, we analysed the data of all 1005 persons who had DNA …