Familial autosomal recessive hypercholesterolemia

Hyperlipidemia [DS:H01635]

Autosomal recessive hypercholesterolemia (ARH) is a rare disorder characterized by elevated low-density lipoprotein (LDL) serum levels, xanthomatosis, and premature coronary artery disease. Several dyslipidemias have been identified which lead to severe primary hypercholesterolemia. Among them, ARH is characterized by clinical symptoms and plasma cholesterol levels intermediate between those found in heterozygous and homozygous familial hypercholesterolemia (FH) [DS:H00155] individuals. ARH patients develop symptomatic coronary artery disease later in life and their xanthomas tend to be large and bulky. In 2001, ARH was found to be caused by mutations in the LDL receptor adaptor protein 1 (LDLRAP1). In ARH, the internalization of the ligand-receptor complex cannot occur and all the LDL receptors accumulate on the cell membrane. In general, ARH patients show a better response to lipid-lowering therapy than the FH patients, and they rarely require LDL apheresis.

Inherited metabolic disease; Cardiovascular disease

nt06320  APOB-LDLR signaling

LDLRAP1 [HSA:26119] [KO:K12474]

PMID:15599766

Canizales-Quinteros S, Aguilar-Salinas CA, Huertas-Vazquez A, Ordonez-Sanchez ML, Rodriguez-Torres M, Venturas-Gallegos JL, Riba L, Ramirez-Jimenez S, Salas-Montiel R, Medina-Palacios G, Robles-Osorio L, Miliar-Garcia A, Rosales-Leon L, Ruiz-Ordaz BH, Zentella-Dehesa A, Ferre-D'Amare A, Gomez-Perez FJ, Tusie-Luna MT

A novel ARH splice site mutation in a Mexican kindred with autosomal recessive hypercholesterolemia.

Hum Genet 116:114-20 (2005)
DOI:10.1007/s00439-004-1192-9

PMID:21513517

Fahed AC, Nemer GM

Familial hypercholesterolemia: the lipids or the genes?

Nutr Metab (Lond) 8:23 (2011)
DOI:10.1186/1743-7075-8-23

PMID:11326085

Garcia CK, Wilund K, Arca M, Zuliani G, Fellin R, Maioli M, Calandra S, Bertolini S, Cossu F, Grishin N, Barnes R, Cohen JC, Hobbs HH

Autosomal recessive hypercholesterolemia caused by mutations in a putative LDL receptor adaptor protein.

Science 292:1394-8 (2001)
DOI:10.1126/science.1060458