[Homozygous hypercholesterolemia - new therapeutic options in cases with complete lack of LDL- receptor].
Homozygous hypercholesterolemia is an extremely rare genetic disorder caused by mutations in the LDL receptor gene or occasionally by mutations in other genes like proprotein convertase subtilisin / kexin 9 (PCSK9). Gold standard of homozygous hypercholesterolemia therapy is apheresis, accompanied by high-dose statin and ezetimibe therapy. The cholesterol-lowering effect can be supported by new agents like inhibitors of microsomal triglyceride transfer protein (lomitapide), or by enhancing LDL catabolism through inhibition of the PCSK9 activity. We present the case of a young woman with homozygous hyperlipidemia due to a mutation c.1200 C> A(p.Tyr400*) in the LDLR gene that introduces a stop-codon at amino acid position 400. This truncated LDLR cannot mediate a membrane-bound uptake of LDL cholesterol. A combined therapy including simvastatin, ezetimibe and apheresis did not lead to satisfactory LDL levels. By adding lomitapide, a dramatic receptor-independent reduction of LDL was achieved.
Klaus Peter
KP
Mellwig
Martin
M
Farr
Jürgen
J
Diekmann
Dieter
D
Horstkotte
Frank
F
van Buuren
D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use; D001781:Blood Component Removal; D018388:Codon, Terminator / Q000235:genetics; D003131:Combined Modality Therapy; D003327:Coronary Disease / Q000097:blood / Q000235:genetics* / Q000628:therapy; D004252:DNA Mutational Analysis; D000069438:Ezetimibe / Q000627:therapeutic use; D005260:Female; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000235:genetics* / Q000628:therapy*; D009204:Myocardial Revascularization; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics*; D019821:Simvastatin / Q000627:therapeutic use
D000924:Anticholesteremic Agents; C473731:BMS201038; D001562:Benzimidazoles; D018388:Codon, Terminator; D011973:Receptors, LDL; D019821:Simvastatin; D000069438:Ezetimibe