Familial xanthomatous hypercholesterolemia: abnormal exogenous lipid metabolism evidenced by the vitamin A test.

Familial xanthomatous hypercholesterolemia is a metabolic disorder associated with high LDL levels attributed to a familial defect in LDL receptor activity. We have previously shown that hyperlipoproteinemia of WHHL rabbits, considered to be a model for heritable hypercholesterolemia, was at least partly of exogenous origin. We have though studied retinyl palmitate (RP) levels 12 h after a standardized mixed meal as a simple test to detect abnormalities of intestinal-derived lipoprotein clearance in 22 familial hypercholesterolemic patients with xanthomatosis (13 of them treated by simvastatin, an HMGCoA reductase inhibitor, and 9 not treated), as compared to a control group (n = 12). Total and LDL cholesterol, plasma triglyceride and apo B levels were significantly higher in patients when compared to controls. Mean RP levels appeared higher in familial hypercholesterolemic patients, when compared to controls, with 6 among 22 patients showing clearly high vitamin A levels and 4 borderline values, whereas high triglyceride levels (> 2 g/l) were detected in only 1 patient. No patients within the group with high vitamin A levels showed an apo E2/E2 phenotype. Vitamin A levels correlated with plasma triglycerides in the whole group of subjects (r = 0.50, p < 0.05). No difference was observed in vitamin A distribution between treated and untreated hypercholesterolemic patients. Our results indicate that the clearance of RP-labeled intestinal lipoproteins is delayed in some xanthomatous familial hypercholesterolemic patients as compared with that of controls. These findings suggest that familial xanthomatous hypercholesterolemia may be heterogenous concerning physiopathological mechanisms inducing hyperlipidemia.

Retinyl palmitate labeled intestinally derived lipoproteins accumulate in the circulation of WHHL rabbits.

The behavior of native retinyl palmitate labeled intestinally derived lipoproteins and their remnants was studied in 8 NZW and 8 WHHL (5 homo- and 3 heterozygote) normal-fed rabbits and in 3 cholesterol-fed NZW, after 1 month of cholesterol feeding, and 3 and 5 months after resuming normal feeding. Palmitate labeled lipoproteins were produced by the intestine after administration of 50,000 IU of Vitamin A, together with olive oil via gastric intubation. Blood was drawn before and 3,6,9,12,24, and in some instances, 48 h later. Retinol (R) and retinyl palmitate (RP) were measured in whole serum and in the chylomicron, d less than 1006, d greater than 1006 less than 1019, d greater than 1019 less than 1063, d greater than 1063 less than 1210 g/ml lipoprotein fractions and in the infranatant. The R content of the serum was almost all concentrated in the infranatant, it did not change during the vitamin A test and was similar in WHHL, and normal- or cholesterol-fed NZW rabbits. In the normal-fed NZW the RP content of the serum increased within 6 h after giving the vitamin A fat meal (peak value less than 200 microgram/100 ml) and then decreased. In the WHHL homozygotes, the RP increased to a much greater degree (peak value 600-1820 micrograms) and for a much longer time, as it was still increased in the 5 cases studied after 24 h, and in 3 cases studied after 48 h. Similar RP curves were obtained in NZW rabbits, after 1 month of cholesterol feeding.(ABSTRACT TRUNCATED AT 250 WORDS)