Family hypercholesterolaemia is a frequent hereditary disease (occurrence in 1 of 200 to 500 persons). It leads without appropriate therapy for the early calcification of the blood vessels and thus to coronary heart disease and ultimately to myocardial infarction or stroke. This disease is undiagnosed in the majority of carriers (according to studies, this is about 80-90% in Europe) because it causes no symptoms for a long time.
Characteristic are elevated values of LDL cholesterol, which, however, are partly in a border area, as also occur in non-genetic forms of hypercholesterolemia. The familial hypercholesterolaemia can be caused by different mutations in different genes. The main genes are the gene for the LDL receptor, for PCSK9 and the APOB gene. Common to all genetic defects is the reduced degradation of LDL cholesterol, resulting in high blood levels and the deposition of this harmful cholesterol molecule in the skin, tendons and (clinically significant) in the coronary arteries.
Up to now, it has been very difficult to diagnose this hereditary disease for laboratory analytical reasons, since the mutation can be caused by a variety of mutations in the 3 mentioned genes (more than 1000 variants are present in the LDL receptor gene alone). By means of the latest methodical developments in the laboratory (namely, the further development of sequencing technology with ever faster parallel sequencing machines, "next generation sequencing" or NGS), it has recently been possible to diagnose familial hypercholesterolemia safely and with justifiable work and financial expenses.
As a combination of dietary change, more exercise and drug therapy (statins or even newly developed and even more potent drugs) leads to a good response, an early diagnosis is very important to avoid the mentioned late sequelae of the disease. In addition, the detection of mutations in the causative genes (e.g., in duplicate mutations) may justify more intensive therapeutic measures (lipid apheresis) if drug measures for lipid reduction are not sufficient.