Loading…

Autosomal recessive hypercholesterolaemia: long-term follow up and response to treatment

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 n...

Full description

Saved in:
Bibliographic Details
Published in:Atherosclerosis 2004-05, Vol.174 (1), p.165-172
Main Authors: Naoumova, Rossitza P., Neuwirth, Clare, Lee, Philip, Miller, J.Paul, Taylor, Kenneth G., Soutar, Anne K.
Format: Article
Language:English
Subjects:
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0021-9150
1879-1484
DOI:10.1016/j.atherosclerosis.2004.01.020