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.
Keywords
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Article info
Publication history
Accepted:
January 26,
2004
Received in revised form:
January 16,
2004
Received:
September 2,
2003
Identification
Copyright
© 2004 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
