Homozygous familial hypercholesterolemia and its management.
Mutations in the low-density lipoprotein (LDL) receptor gene cause familial hypercholesterolemia. In homozygous familial hypercholesterolemia, both genes for the LDL- receptor are mutated and LDL levels are markedly elevated. High-density lipoprotein cholesterol concentration is often reduced and lipoprotein(a) levels are high when corrected for apolipoprotein(a) isoforms. Cutaneous and tendinous xanthomata develop in childhood and are the most common reason for initial presentation. The diagnosis can be confirmed by analysis of LDL-receptor genes or studies of LDL receptor function in cultured cells. Severe aortic and coronary atherosclerosis usually occurs within the first or second decades of life. Left ventricular outflow tract obstruction may be at the level of the aortic valve or the supravalvar aorta. Treatment for the hyperlipidemia is with plasmapheresis, high-dose statins, and ezetimibe. Liver transplantation reverses the metabolic defect but requires chronic immunosupression, and rejection may still occur. Liver transplantation is indicated if cardiac transplantation becomes necessary. Portocaval shunt may still play a role in patients with coronary artery disease who do not have access to plasmapheresis. Gene therapy is currently not practicable but is being actively developed.
Marais
Adrian David
AD
Lipidology Division of Internal Medicine and MRC Cape Heart Group, University of Cape Town Health Science Faculty, Observatory, South Africa. dmarais@capeheart.uct.ac.za
Firth
Jean Catherine
JC
Blom
Dirk Jacobus
DJ
D015415:Biomarkers / Q000097:blood; D019468:Disease Management; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006720:Homozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*
D015415:Biomarkers