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Electron Microscopic Structure of Serum Lipoproteins from Patients with Fish Eye Disease

The structure and composition of lipoprotein fractions from two patients with fish eye disease were examined. The composition of very low density lipoproteins (VLDL) was normal, although total mass was greatly elevated. The mean particle sizes of the VLDL were 44.6 ± 22.2 and 42.8 ± 19.8 nm for Patients 1 and 2, respectively. Intermediate density lipoprotein (IDL) concentrations in patients were elevated and contained increased triglycerlde content; particle sizes for Patients 1 and 2 were 29.4 ± 3.5 nm and 28.0 ± 4.1 nm, respectively. In both patients, the trlglycerlde/cholesteryl ester ratio in LDL was approximately tenfold higher than In normal individuals; however, the LDL particles were somewhat smaller in diameter (23.5 ± 3.0 nm for Patient 1 and 23.3 ± 3.8 nm for Patient 2) than those of controls (25.8 ± 3.0 nm and 24.9 ± 3.4 nm). In both patients, large vesicular structures were occasionally encountered in the LDL region. The high density lipoprotein (HDL) fraction of fish eye disease patients showed the greatest abnormalities. Not only was the total HDL concentration extremely low (approximately 10% of control levels), but unesterlfied cholesterol was Increased relative to cholesteryl ester. Particle morphology was heterogeneous; the major HDL species was a small spherical particle with a diameter of 7.6 nm. Discoldal particles with a thickness of 4.4 nm and diameters between 17.4 and 20.8 nm were also present, together with large (40-90 nm) vesicles. Since lecithin cholesterol acyltransferase activity levels appear normal In fish eye disease patients, the accumulation of these unusual structures must be due to other metabolic defects such as low total apollpoprotein A-l content and/or association of apolipoprotein E with unesterified cholesterol-rich particles that inhibit their esterification.