Hypocholesterolaemia in
infantile Refsum disease (IRD) may link peroxisomes and
lipoprotein metabolism. In our patient, plasma
cholesterol levels were reduced to 26% and 29% of control in
LDL and HDL fractions, respectively. Plasma
apolipoproteins B-100 and A-I levels were 52% and 66% of controls, respectively. In the kindred, plasma
cholesterol concentration was 61-73% of controls. The
HDL-cholesterol/
apo A-I ratios were: patient 0.12; kindred 0.17; controls 0.28. Analysis of the IRD patient's
lipoprotein revealed compositional abnormalities in all fractions. The patient's
LDL demonstrated a substantial reduction in its
lipid-to-
protein ratio. Alterations in plasma
lipoproteins affect their interaction with macrophages. Upon incubation of the patient's
LDL with J-774 macrophages, its cellular uptake, measured as
cholesterol esterification rate, was only 66% of a control rate. The abnormal
LDL of the IRD patient showed also only 25% of control susceptibility to in vitro oxidation. Studies of cellular
cholesterol metabolism in the patient's monocyte-derived macrophages (MDM) showed 57% increased
cholesterol esterification rate in comparison to normal MDM. The possible link between
lipoprotein abnormalities and monocyte-macrophage
cholesterol metabolism is discussed.