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 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.
Naoumova
Rossitza P
RP
Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK. rossi.naoumova@csc.mrc.ac.uk
Neuwirth
Clare
C
Lee
Philip
P
Miller
J Paul
JP
Taylor
Kenneth G
KG
Soutar
Anne K
AK
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
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D011973:Receptors, LDL