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 qu alitative perturbations of apo B- and apo A-I-containing plasma lipopr oteins. Marked particle heterogeneity has been detected over the low-d ensity range (d = 1.019-1.063 g/ml), involving lipoprotein(X) (LP-X) a nd large molecular weight LDL (LM-LDL). We describe the chromatographi c fractionation and characterization of the major particle species dis tributed within the low-density interval in a new French LCAT-deficien t family. Detailed analyses of the plasma lipoprotein and apolipoprote in spectrum are reported. The plasma lipoproteins were enriched in une sterified cholesterol and phospholipids with markedly reduced concentr ations of cholesteryl esters. By a combination of gel filtration and a ffinity chromatography on heparin-sepharose, the heterogeneous mixture of low-density particles was resolved into three distinct particle po pulations: LP-X (diameter 400 Angstrom) corresponding to LM-LDL, an ap o A-I and albumin-containing particle similar to LP-X, (diameter 300 A ngstrom), and cholesteryl ester-deficient (0.9%) triglyceride-rich (58 .4%) LDL containing apo B-100 (diameter 260-270 Angstrom). Use of affi nity chromatography allowed separation of HDL-like particles (diameter 140- 160 Angstrom) which were rich in free cholesterol (21.4%) and ph ospholipids (52.9%) and which were isolated in association with LP-X u pon gel filtration chromatography. Ultracentrifugal density gradient a nalysis of plasma from the LCAT-deficient subject over a period of 3 y ears showed a net shift of the lipoprotein distribution in the low den sity range due to an increase in plasma LP-X levels. We propose that t he presence of LP-X in the plasma is correlated with a progressive alt eration in the renal function recently observed in this patient.