Familial Xanthomatous Hypercholesterolemia: Abnormal Exogenous Lipid Metabolism Evidenced by the Vitamin A Test

Abstract

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.

A single-day mouse mesenteric lymph surgery in mice: an updated approach to study dietary lipid absorption, chylomicron secretion, and lymphocyte dynamics

“…Diseases where dietary fat absorption is defective include inflammatory bowel disease, cystic fibrosis, short bowel syndrome, intestinal wasting diseases 20,21 , and lysosomal acid lipase deficiencies (like Wolman disease or cholesterol ester storage disease) [22][23][24][25] . Defective dietary fat absorption is not simply an inability to extract fat from a meal J o u r n a l P r e -p r o o f (since the gut can adapt to defects in surface area and length), it also results in the use of noncanonical absorption pathways which form abnormal and potentially dysfunctional chylomicrons.…”