Familial lipoprotein lipase and apolipoprotein C-II deficiency Lipoprotein and apoprotein analysis, adipose tissue and hepatic lipoprotein lipase levels in seven patients and their first degree relatives

Abstract

Plasma lipids, lipoproteins, tissue lipoprotein lipase (LPL) and hepatic lipase (H-TGL) were studied in 7 patients with familial hyperchylomicronemia from four different families. Their first-degree relatives were also studied. The patients were heterogeneous for the genetic defect; LPL activity was absent in five patients (LPL deficiency) but normal in two. However, these two did not have apo C-II, the physiological activator of LPL (C-II deficiency). There were no significant differences in the clinical picture between patients with LPL deficiency and C-II deficiency. In both mutants, marked hypertriglyceridemia was due to an accumulation of lipoproteins of density < 1.006 g/ml. The LDL fraction was very reduced and abnormal in composition, presenting a CH TG ratio of 0.5. The plasma apolipoprotein B (apo B) level was low (67 ± 5.5 mg/dl) and was transported mainly in the VLDL fraction (26 ± 3.2 mg/dl) rather than in the LDL fraction (15 ± 1.4 mg/dl). Very low levels of cholesterol and apolipoprotein A-I in HDL subfractions HDL 2 and HDL 3 were also recorded. Only 3 out of the 24 first-degree relatives of patients with LPL deficiency showed even a small increase in plasma triglycerides, but 15 had low or low to normal LPL values. H-TGL levels were normal in all subjects. The 4 first-degree relatives of C-II deficiency patients showed normal levels of plasma lipids, LPL and H-TGL, and 2 children of 1 patient showed normal distribution of apo C peptides in their VLDL. A block in chylomicron catabolism, due to the absence of LPL or apo C-II, may lead to a massive accumulation of lipoproteins with a density < 1.006 g/ml, and a drastic reduction in the LDL and HDL fractions. Low LPL values in the first-degree relatives of LPL deficiency patients might represent a biochemical marker for healthy carriers of LPL deficiency.