title: Homozygous familial hypercholesterolemia: current perspectives on diagnosis and treatment.
abstract: Homozygous familial hypercholesterolemia (HoFH) is an autosomal co-dominant disease resulting from mutations in both copies of the low-density lipoprotein receptor (LDLR) gene. Mutations in 3 other associated genes, proprotein convertase subtilisin/kexin type 9, apolipoprotein B (APOB), and, more rarely, the autosomal recessive hypercholesterolemia adaptor protein, may lead to a similar phenotype with varying severity. HoFH patients have aggressive cardiovascular disease that develops from birth due to severe LDLR defects, resulting, in turn, in excess production of Apo B-containing atherogenic lipoproteins (low-density lipoprotein [LDL] and lipoprotein(a)). The condition is characterized by exceptionally high LDL cholesterol levels, cutaneous and tendon xanthomas, and valvular and supravalvular stenosis, and accelerated atherosclerosis often manifests in the first 2 decades of life. Treatment typically involves lipid-modifying medical therapy as well as mechanical removal of plasma LDL by means of apheresis. Although statins have afforded survival into the third and fourth decades of life, further therapeutic advancements currently under investigation promise hope of further improvements in survival and improved quality of life. The purpose of this review is to provide current perspectives on diagnosis and therapy in an effort to encourage early recognition and treatment of this rare but severe disease.
authors.affiliation: Carbohydrate & Lipid Metabolism Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. frederick.raal@wits.ac.za
authors.forename: Frederick J
authors.initials: FJ
authors.lastname: Raal
authors.forename: Raul D
authors.initials: RD
authors.lastname: Santos
mesh_terms: D000293:Adolescent; D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D001781:Blood Component Removal; D002318:Cardiovascular Diseases / Q000235:genetics / Q000517:prevention & control; D008078:Cholesterol, LDL / Q000097:blood; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*; D008297:Male; D009154:Mutation; D010641:Phenotype; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000924:Anticholesteremic Agents; D015415:Biomarkers; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011973:Receptors, LDL