Hypercholesterolemia familial autosomal dominant E78.0

Most frequent autosomal dominant inherited monogenetic hyperlipoproteinemia (type II according to Fredrickson) with development of tuberous xanthomas at elbows, gluteal and prepatellar. Furthermore, there are also coarse tendon xanthomas of the Achilles and finger extensor tendons. In homozygotes, which become ill in early childhood, papular xanthomas of the skin and tendons are found in 100% of cases. Only in this group also plane xanthomas in the interdigital folds occur.

Xanthelasma

Early occurring Arcus lipoides corneae.

Eruptive xanthomes are rather rare.

Coronary circulatory disturbances, mitral or aortic vitium due to cholesterol accumulation.

52-76% of patients with monogenetic hypercholesterolemia fall into this phenotype.

Autosomal dominant inherited LDL receptor defects (LDLR). So far, mutations in three genes have been discovered as causes, all three of which influence the function of the LDL receptor :

• LDL receptor gene (LDLR)
• ApoB gene
• PCSK9 gene.

The lack of an effectively functioning LDL receptor system leads to increased levels of modified and overaged LDL in the blood plasma. These LDL particles are alternatively taken up by macrophages through scavenger receptors. This constellation leads to the formation of xanthelasma, xanthoma, and atheromatous vascular lesions. Remark: >70% of LDL receptors are localized in the liver.

PCSK9-associated hypercholesterolemia is caused by a pathogenic gain-of-function (GOF) variant in the PCSK9 gene. This results in excessive degradation of LDLR molecules and thus (markedly) elevated LDL cholesterol levels.

Clear serum. Excessive increase of cholesterol and cholesterol esters.

Total cholesterol for heterozygotes >300mg/dl, for homozygotes >600mg/dl.

LDL cholesterol for heterozygotes between 250-400mg/dl, for homozygotes between 500-1200 mg/dl.

Plasma triglycerides are in the normal range.

Initially, a low-fat, low-cholesterol, high-fiber diet and a diet rich in oat bran (health food store). If dietary measures are not sufficient, lipid-lowering drugs such as lovastatin, bezafibrate, fenofibrate as well as nicotinic acid or anion exchangers,