Hyperapobetalipoproteinemia in a kindred with familial combined hyperlipidemia and familial hypercholesterolemia

Abstract

A child showed a type IIb lipoprotein pattern and triglyceride-enriched cutaneous xanthomas before 1 year of age. The proband and 9 of 18 relatives had elevated plasma levels of low density lipoprotein (LDL) B protein; of these nine relatives, four had elevated LDL of increased density while five had elevated LDL of normal density. Compared with normal LDL, LDL of increased density had less cholesteryl ester and free cholesterol, more apolipoprotein B and triglyceride, and a lower molecular weight and flotation rate (Sf degrees). Patients with LDL of increased density had higher mean plasma levels of triglycerides, very low density lipoproteins, and intermediate density lipoproteins, but lower levels of high density lipoproteins than those with elevated LDL of normal density. Multiple lipoprotein patterns in the father's family suggested the presence of familial combined hyperlipidemia (FCH). The mother of the proband and two of her relatives had type IIa lipoprotein patterns and tendon xanthomas, compatible with familial hypercholesterolemia (FH). High affinity binding, internalization, and degradation of 125I LDL in cultured fibroblasts from the proband and his mother were reduced two- to threefold compared with normal cells, while LDL receptor activity in the proband's father was normal. This unusual proband has apparently inherited both FCH and FH.