On the Protein Defect in Abetalipoproteinemia

The plasma lipoproteins from a patient with abetalipoproteinemia were delipidated and fractionated; the lipid-free proteins (apoproteins) were compared by physical, chemical and immunological technics with the apoproteins from normal subjects. It was established that the major protein constituents of the very low-density lipoproteins, other than apoLP-ser, and the two predominant proteins of the high-density lipoproteins are present in plasma in abetalipoproteinemia and are identical to the corresponding apoproteins from normal subjects. As previously shown, low-density lipoprotein (LDL) and its principal protein component (or components), here designated apoLP-ser, were not detected by immunological tests. These findings indicate that the primary biochemical lesion in abetalipoproteinemia is a selective one affecting the main apoprotein (or proteins) of LDL. ABETALIPOPROTEINEMIA is an inherited disease whose major clinical manifestations are severe hypolipidemia, retinitis pigmentosa, cerebellar ataxia, acanthocytosis and fat malabsorption.^{1 2 3 4 5 6 7} The plasma concentrations of both cholesterol and triglyceride are singularly low, and three of the four major families of plasma lipoproteins are absent. These are chylomicrons, the very low-density (VLDL) and the low-density (LDL) lipoproteins.⁸ When the plasma is subjected to ultracentrifugation, no lipid or protein is detected at the density limit for chylomicrons and VLDL (less than 1.006 g per milliliter),⁸ but small quantities of lipoproteins may be found in the density range of LDL that are immunochemically indistinguishable.