Identification of lipoprotein families in a variant of human plasma apolipoprotein A deficiency

Abstract

This study describes the plasma lipoprotein system of a 48-year-old female patient with diffuse plane xanthoma and a deficiency of ApoA, the major apolipoprotein in HDL. In addition to the skin lesions, the patient exhibited hepatomegaly, corneal opacity and coronary insufficiency. Her tonsils were normal in appearance. Histochemical tests revealed intracellular deposition of free and ester cholesterol in the foam cells of skin lesions and rectal tumors. The patient had normal cholesterol and variable but elevated triglyceride levels in the plasma. The concentration of HDL was 1% of that reported for normal female subjects. In contrast, the concentration of VLDL was five times and that of LDL₁ ten times higher than those of normal subjects. Increased concentrations of VLDL and LDL₁ may be related to a reduced level of lipoprotein lipase. The level of LDL₂ was normal, but its composition was characterized by a relatively high content of triglyceride and protein and a low content of cholesterol ester and phospholipid. The fatty acid composition of cholesterol esters in VLDL, LDL₁ and LDL₂ was normal. Quantitative determination of apolipoproteins reveal increased levels of serum ApoB, C-III and ApoE; these apolipoproteins were present almost exclusively in VLDL and LDL. On the other hand concentration levels of A-I, A-II and ApoD represented 1%, 20% and 50%, respectively, of those found in normals. In contrast to the normal distribution, 75% of the A-II and ApoD were present in LDL and 85% of A-I in VHDL. HDL consisted of small amounts of LP-B, LP-C and LP-D. Although the present case and Tangier disease share the deficiency of ApoA, they differ in several clinical and biochemical parameters. To emphasize this common biochemical lesion, we propose that these clinical entities be referred to as familial ApoA or LP-A deficiency.

Key Words:

• electroimmunoassay
• foam cells
• lipoprotein lipase
• polyacrylamide gel electrophoresis
• Tangier disease