Familial lecithin:cholesterol acyltransferase deficiency: further resolution of lipoprotein particle heterogeneity in the low density interval.

Patients presenting with a familial deficiency of lecithin:cholesterol acyltransferase (LCAT) typically exhibit multiple quantitative and qualitative perturbations of apo B- and apo A-I-containing plasma lipoproteins. Marked particle heterogeneity has been detected over the low-density range (d = 1.019-1.063 g/ml), involving lipoprotein(X) (LP-X) and large molecular weight LDL (LM-LDL). We describe the chromatographic fractionation and characterization of the major particle species distributed within the low-density interval in a new French LCAT-deficient family. Detailed analyses of the plasma lipoprotein and apolipoprotein spectrum are reported. The plasma lipoproteins were enriched in unesterified cholesterol and phospholipids with markedly reduced concentrations of cholesteryl esters. By a combination of gel filtration and affinity chromatography on heparin-sepharose, the heterogeneous mixture of low-density particles was resolved into three distinct particle populations: LP-X (diameter 400 A) corresponding to LM-LDL, an apo A-I and albumin-containing particle similar to LP-X2 (diameter 300 A), and cholesteryl ester-deficient (0.9%) triglyceride-rich (58.4%) LDL containing apo B-100 (diameter 260-270 A). Use of affinity chromatography allowed separation of HDL-like particles (diameter 140-160 A) which were rich in free cholesterol (21.4%) and phospholipids (52.9%) and which were isolated in association with LP-X upon gel filtration chromatography. Ultracentrifugal density gradient analysis of plasma from the LCAT-deficient subject over a period of 3 years showed a net shift of the lipoprotein distribution in the low density range due to an increase in plasma LP-X levels. We propose that the presence of LP-X in the plasma is correlated with a progressive alteration in the renal function recently observed in this patient.