Abnormalities of High Density Lipoproteins in Abetalipoproteinemia*

Abstract

Summary. Detailed studies of the high density lipoproteins from three patients with abetalipoproteinemia have revealed the following principal abnormalities: 1) High density lipoprotein 3 (HDL3) is reduced in both absolute and relative concentration, although HDL2 is present in normal amounts.2) The phospholipid distribution of both HDL fractions is abnormal, with low concentrations of lecithin and an increased percentage (though normal absolute quantity) of sphingomyelin. 3) In both HDL fractions, lecithin contains less linoleate and more oleate than normal. The cholesteryl esters are also low in linoleic acid, and the sphingomyelin is high in nervonic acid. Dietary intake influences the linoleic acid concentration within 2 weeks, and perhaps sooner, but the elevated sphingomyelin nervonic acid is little affected by up to 6 months of corn oil supplementation. Qualitatively similar changes in fatty acid composition, but not phospholipid distribution, are also found in other malabsorption states.The available evidence suggests that the abnormally low levels of HDL3 and the deranged phospholipid distribution are more specific for abetalipoproteinemia than the fatty acid abnormalities. However, the absence of these abnormalities in obligate heterozygous subjects makes their relationship to the primary defect of abetalipoproteinemia difficult to assess.

A study of the abnormal lipoproteins in abetalipoproteinemia.

“…Cooper and Guldbrandsen (32) In all of our five subjects significant anomalies were also noted in the HDL class. These anomalies were characterized by: (a) marked reduction of the total plasma concentration of HDL, particularly affecting the HDL3 subclass, as has been noted previously by Jones and Ways (27); (b) a peculiar behavior of these particles when they were subjected to analytical ultracentrifugation or density gradient analysis in high salts; (c) unusual polypeptide distribution; (d) abnormality in sialylation of apo C-III and (e) abnormal lipid composition. The low plasma concentration of HDL in ABL remains unexplained but must be related to an imbalance of the mechanisms regulating their production, secretion, and degradation.…”

“…The present study has provided additional evidence that the metabolic defect in ABL is a complex one (27) and affects all classes of plasma lipoproteins, although to varying degrees. The genetic nature of the observed lipoprotein abnormalities appears to be supported by the fact that these abnormalities were expressed equally in all of the patients studied regardless of sex, age, ethnic group, nutritional or drug regime, or disease state.…”

Normotriglyceridemic abetalipoproteinemia. absence of the B-100 apolipoprotein.

“…Despite the presence of triglyceride-rich lipoproteins in plasma, the syndrome which we describe here shares a number of features with the other two forms of abetalipoproteinemia, recessive abetalipoproteinemia and homozygous hypobetalipoproteinemia. In both, the ratio of sphingomyelin to phosphatidylcholine in plasma is increased (2,34). In the disorder we describe, this phenomenon is evident in the d < 1.006 g/Cm3 lipoprotein fraction as well as in the HDL.…”

“…In that disorder, normal chylomicrons, very low density lipoproteins (VLDL),1 and low density lipoproteins (LDL) are absent from plasma. A small amount of an abnormal lipoprotein, which can be concentrated from the low density untracentrifugal interval, appears to be derived from high density lipoproteins (HDL) (1)(2)(3)(4). Clinical features include severe malabsorption of triglycerides (5), acanthocytosis of erythrocytes (often with autohemolysis) (1,6), de-ficiency of tocopherols and often other fat soluble vitamins in plasma, retinopathy (7), and progressive neurological disease (1).…”

Plasma lipoproteins in familial lecithin:cholesterol acyltransferase deficiency: lipid composition and reactivity in vitro

“…Measurements of cholesterol and phospholipid were performed as described previously (8). Tri (14)(15)(16)(17). They show that the following significant relationships exist: the ratio of cho-10.01 N Tris HCl, 0.001 M EDTA, 0.14 N NaCl, pH 7.4.…”