Coexisting dysbetalipoproteinemia and familial hypercholesterolemia: Clinical and laboratory observations

Abstract Type III dysbetalipoproteinemia and familial hypercholesterolemia (FH) are two metabolic disorders giving rise to severe disturbances of lipid homeostasis and premature atherosclerosis. Both metabolic abnormalities have a genetic basis and co-occurrence in the same patient has seldom been described. Because of the unique structure of the French Canadian population, there was an opportunity to observe patients with both dysbetalipoproteinemia (E2/2 homozygotes) and FH ( N =14) and to compare their clinical data with that of patients with type III ( N =75), patients with FH ( N =42). The E2/2-FH patients displayed clinical features of both metabolic disorders: palmar, Achilles and/or extensor tendon xanthomas, a prevalence of coronary artery disease (CAD) equal to that seen in type III, but lower than that observed in FH and a high prevalence of peripheral vascular disease (PVD) in both genders. A higher prevalence of carotid disease than that observed in the two other conditions was seen in women only. In men, total cholesterol level was similar to that observed in FH, but higher than in type III, whereas in women, it was not different among the three groups. In both genders, triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) levels were intermediate between type III and FH, with a very low density lipoprotein-cholesterol (VLDL-C)/TG ratio>0.7 and the presence of β-VLDL on electrophoresis. Presence of a low density lipoprotein receptor, LDL-R, mutation should be suspected in a type III patient with a LDL-C level above 3.0 mmol/l and a family history of premature CAD. In the group of patients studied, the coexistence of dysbetalipoproteinemia and heterozygous FH does not appear to increase the prevalence of cardiovascular complications above that observed among control type III or control E3/3-FH patients. Thus, the presence of two e2 alleles in these patients affects the expression of the abnormal LDL-R allele and the resulting phenotype substantiates the non additive effects of alleles at these two loci (epistasis).