A 14-year-old girl was admitted to our hospital, complaining of abdominal pain. Her serum was milkish, the triglyceride (TG) level was 3, 548mg/dl and the total cholesterol (T-Ch) level was 316mg/dl. Agarose gel electrophoresis and sequential preparative ultracentrifugation revealed markedly increased levels of chylomicron and VLDL. Postheparin plasma (PHP) lipoprotein lipase (LPL) activity was 0.93μmol/ml/hr (control: 9.23±0.67) and serum level of apolipoprotein C-II (Apo C-II) was 9.2mg/dl (control: 3.0±0.8). Oral glucose tolerance test was normal.
Laboratory examinations showed the increased levels of serum TG in her parents, although her mother's hypertriglyceridemia was later normalized. Serum lipid levels of her two sisters were within normal limits. Serum lipoprotein fractionation of her father also demonstrated high levels of chylomicron and VLDL. PHP LPL activity was very low (1.16μmol/ml/hr) in her father and moderately decreased in her mother and second sister (5.1 and 3.2μmol/ml/hr). Her father's subcutaneous adipose tissue LPL activity was 3.35μmol/g/hr (control: 2.46±1.82). Hence, this family was diagnosed as having primary type I hyperlipoproteinemia.
Primary type I hyperlipoproteinemia is currently considered to have three subclasses: 1) familial LPL deficiency, 2) familial Apo C-II deficiency, and 3) a circulating inhibitor of LPL activity. The presence of normal or high levels of serum Apo C-II excluded the possibility of a familial Apo C-II deficiency. Despite the normal LPL activity in her father's adipose tissue, his PHP LPL activity was markedly decreased, leading us to examine an inhibitor of LPL activity according to Brunzell's method. Normal postheparin lipolytic activities were inhibited by about 20% and 10% by the addition of 0.4ml of patient's and her father's lipoprotein free sera, respectively. Hence, we concluded that the patient and her father had primary type I hyperlipoproteinemias due, to a circulating inhibitor of LPL activity. However, it was difficult to explain the following two points: 1) PHP LPL activity was also low in her mother and second sister, and 2) inhibiting activities of the patient's and her father's sera on LPL activity were not sufficiently potent compared with the extremely low PHP LPL activities. For these points, we proposed the possibility that in addition to LPL inhibitor this family had familial LPL deficiency which was transmitted to the parents and second sister in heterozygous form.