title: Autosomal recessive hypercholesterolaemia: long-term follow up and response to treatment.
abstract: Autosomal recessive hypercholesterolaemia (ARH) is caused by mutations in ARH on chromosome 1p35-36, encoding a putative adaptor protein. Mutations in the gene prevent normal internalisation of the low density lipoprotein (LDL) receptor by cultured lymphocytes and monocyte-derived macrophages, but not skin fibroblasts. This newly identified disorder is characterised by severe hypercholesterolaemia, large tendon, tuberous and planar xanthomas and premature atherosclerosis. We describe long-term (9-23 years) follow up and response to treatment of eight subjects with ARH from four families (Turkish/Lebanese, Indian-Asian, English and Italian). The clinical phenotype of ARH is similar to that of classical homozygous familial hypercholesterolaemia (FH) caused by mutations in the LDL-receptor gene but is more variable, less severe and is more responsive to lipid-lowering therapy with bile acid sequestrants and/or HMG-CoA reductase inhibitors. The latter reduced total serum cholesterol by up to 60% and the former by 20-35%. The cardiovascular complications of premature atherosclerosis seem to be delayed in some individuals and the involvement of the aortic root and valve are rarer in comparison with homozygous FH.
authors.affiliation: Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. rossi.naoumova@csc.mrc.ac.uk
authors.forename: Rossitza P
authors.initials: RP
authors.lastname: Naoumova
authors.forename: Clare
authors.initials: C
authors.lastname: Neuwirth
authors.forename: Philip
authors.initials: P
authors.lastname: Lee
authors.forename: J Paul
authors.initials: JP
authors.lastname: Miller
authors.forename: Kenneth G
authors.initials: KG
authors.lastname: Taylor
authors.forename: Anne K
authors.initials: AK
authors.lastname: Soutar
mesh_terms: D000328:Adult; D002648:Child; D003324:Coronary Artery Disease / Q000517:prevention & control; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D008077:Lipoproteins, LDL / Q000032:analysis / Q000187:drug effects; D008297:Male; D010375:Pedigree; D011973:Receptors, LDL / Q000235:genetics; D018570:Risk Assessment; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D011973:Receptors, LDL