Increased catabolism of VLDL-apolipoprotein B and synthesis of bile acids in a case of hypobetalipoproteinemia

A 29-year-old man is described who has reduced concentrations of low density lipoprotein (LDL)-cholesterol seemingly due to an unusual variant of hypobetalipoproteinemia. The patient developed retinitis pigmentosa at age 14. When studied at age 28, his total cholesterol was 104 mg/dL, triglycerides 58 mg/dL, LDL-cholesterol 44 mg/dL, and HDL-cholesterol 51 mg/dL. Lipid and lipoprotein levels of his parents and sister were normal. His excretion of bile acids (13.9 mg/kg/d) was markedly elevated at about three times normal, although absorption rates of cholesterol and bile acids appeared to be in the normal range. His high excretion of bile acids equates to a threefold increase in bile acid synthesis. Isotope kinetic studies of his lipoproteins produced unexpected findings. Total production of VLDL-apolipoprotein B (apo B) was estimated to be 20.8 mg/kg/d, which was in the normal range. Synthesis of VLDL-triglycerides was also normal at 12.0 mg/kg/h. However, 75% of VLDL-apo B was removed directly from the circulation, which was much higher than values for direct removal of VLDL-apo B in control subjects. His production rate of LDL-protein (5.2 mg/kg/d) consequently was below normal, although his fractional catabolic rate for LDL (0.40 pools/d) was not distinctly elevated. These data suggest that the patient's hypobetalipoproteinemia was due to increased direct removal of VLDL remnants and not to reduced synthesis of VLDL-apo B; this abnormality may have been the result of enhanced activity of LDL receptors, which in turn was secondary to increased synthesis of bile acids.