A study of the abnormal lipoproteins in abetalipoproteinemia.

Abstract

A B S TRA CT The serum lipoproteins of five patients with abetalipoproteinemia (ABL) were separated by ultracentrifugation and then analyzed either intact or after delipidation. In accord with previous findings, all of the patients lacked serum particles with the characteristics of normal low-density lipoproteins (LDL) and of the LDL apoprotein as assessed by immunochemical methods. Each patient exhibited on every examination an abnormal particle, "LDL", which had the fotational properties of LDL, the polypeptide makeup of highdensity lipoproteins HDL, the spectral and morphological characteristics of neither LDL nor HDL, and a relatively low content of cholesteryl esters. The HDL were abnormal in having a marked decrease in their total plasma content, an altered proportion of the subclasses HDL2 and HDLa, and a peculiar polypeptide distribution, comprising both normal and additional components, usually not seen in normal controls. The patients also exhibited a decrease of plasma lecithin-cholesterol acyl transferase (LCAT) activity which probably accounted for the low content of cholesteryl esters in both "LDL" and HDL, and in turn for the unusual appearance of "LDL" on electron microscopy.

Role of Apolipoprotein E-containing Lipoproteins in Abetalipoproteinemia

“…(26) (28,29): the fractions richl irn apoE-contained particles of larger mean diameter and higher cholesterol/protein ratio than did those poor in apoE. As had b)een inoted when 1-H1)12 was isolated by zonal ultracenitrifugation (30), we found that the HDI-2 of abetalipoproteinemia was of larger mean particle size thain the HDL2 of normal volunteers.…”

Normotriglyceridemic abetalipoproteinemia. absence of the B-100 apolipoprotein.

“…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).…”

Metabolic Studies in an Unusual Case of Asymptomatic Familial Hypobetalipoproteinemia with Hypoalphalipoproteinemia and Fasting Chylomicronemia

“…It is possible that the low apoE3/apoE2 ratio in our patients accounts for some of the unusual features in his case. A deficiency of apoC-III1 has been reported in abetalipoproteinemia (4,51) but this is the first reported example in apoC-III, deficiency in hypobetalipoproteinemia. Whether it represents a primary defect or a secondary consequence of low LDL levels is not known.…”

“…In this paper we present the results of intensive studies in an asymptomatic man in his seventh decade with a familial hypobetalipoproteinemic syndrome different from those previously reported in a number of respects: (a) extremely low LDL levels (4)(5)(6)(7)(8) (11).…”

“…Ordinary methods fail to reveal low density lipoprotein (LDL),1 very low density lipoprotein (VLDL), or chylomicrons. By concentrating the fraction with d < 1.063 it is possible to demonstrate lipoproteins but these are abnormal in composition and structure, i.e., they do not represent normal LDL or VLDL (1)(2)(3)(4). This apparently total deficiency of lipoproteins containing apoprotein B is associated with a severe clinical syndrome, usually apparent in infancy (5).…”