Background Patients with lipoprotein lipase deficiency usually present with chylomicronemia in childhood. The syndrome has been considered nonatherogenic primarily because of the low levels of low-density lipoprotein (LDL) cholesterol. We prospectively evaluated patients with lipoprotein lipase deficiency for atherosclerosis. Methods Evidence of carotid, peripheral, and coronary atherosclerosis was sought in four patients (two men and two women) with the phenotype of familial chylomicronemia by clinical examination over a period of 14 to 30 years and by Doppler ultrasonography, ultrasonography, and exercise-tolerance testing after the age of 40. Angiography was performed when indicated. Lipoprotein lipase deficiency was assessed in vivo and in vitro by functional assays and DNA-sequence analysis. Results All four patients had a profound functional deficiency of lipoprotein lipase with a reduced enzymatic mass due to missense mutations on both alleles of the lipoprotein lipase gene. In all four patients, peripheral or coronary atherosclerosis (or both) was observed before the age of 55. Despite following a low-fat diet in which fat composed 10 to 15 percent of the daily caloric intake, the patients had hypertriglyceridemia (mean [+/-SD] triglyceride level, 2621+/-1112 mg per deciliter [29.59+/-12.55 mmol per liter]), low plasma levels of high-density lipoprotein cholesterol (17+/-7 mg per deciliter [0.43+/-0.18 mmol per liter]), and very low levels of LDL cholesterol (28+/-16 mg per deciliter [0.72+/-0.41 mmol per liter]). Three patients had one risk factor for atherosclerosis, whereas in one male patient, heavy smoking and diabetes were associated with an accelerated course of the disease. Conclusions Premature atherosclerosis can occur in patients with familial chylomicronemia as a result of mutations in the lipoprotein lipase gene. Defective lipolysis may increase susceptibility to atherosclerosis in humans. (C) 1996, Massachusetts Medical Society.
