Familial hypo-β-lipoproteinemia: A genetic disorder of lipid metabolism with nervous system involvement

Abstract

A previously undescribed inborn error of lipid metabolism has been demonstrated in thirteen members of a kinship. The disorder was genetically transmitted in an autosomal dominant fashion. This abnormality, termed familial hypo-β-lipoproteinemia, consisted of a great reduction of serum β-lipoprotein content. Serum levels of cholesterol and phospholipid were low, whereas the concentrations of serum triglyceride were normal or low and that of α-lipoprotein normal. Vitamin E levels were decreased in five of the eleven persons so tested. Nine persons, all with serum cholesterol levels less than 100 mg. per 100 ml., showed acanthocytic red blood cells. These cells could be transformed to cells with normal forms by the in vitro addition of serum from hyperlipemic or hypercholesteremic persons. The clinical manifestations of this disorder are variable, and may be correlated with the severity of the biochemical abnormality. In its most severe form, as shown by the propositus, there is lack of responsiveness to local anesthetic agents, and signs and symptoms of a progressive demyelinating disorder affecting the central nervous system. Fasting peroral jejunal biopsy material from the propositus contained significant deposits of neutral fats beneath the lamina propria and in endothelial cells of capillaries containing lipid-laden mononuclear cells. The material presented suggests that hypo-β-lipoproteinemia may be an etiologic factor in some demyelinating disorders.