PREMATURE ATHEROSCLEROSIS IN PATIENTS WITH FAMILIAL CHYLOMICRONEMIA CAUSED BY MUTATIONS IN THE LIPOPROTEIN-LIPASE GENE

Background Patients with lipoprotein lipase deficiency usually present with chylomicronemia in childhood. The syndrome has been considered n onatherogenic primarily because of the low levels of low-density lipop rotein (LDL) cholesterol. We prospectively evaluated patients with lip oprotein lipase deficiency for atherosclerosis. Methods Evidence of ca rotid, peripheral, and coronary atherosclerosis was sought in four pat ients (two men and two women) with the phenotype of familial chylomicr onemia by clinical examination over a period of 14 to 30 years and by Doppler ultrasonography, ultrasonography, and exercise-tolerance testi ng after the age of 40. Angiography was performed when indicated. Lipo protein lipase deficiency was assessed in vivo and in vitro by functio nal assays and DNA-sequence analysis. Results All four patients had a profound functional deficiency of lipoprotein lipase with a reduced en zymatic mass due to missense mutations on both alleles of the lipoprot ein lipase gene. In all four patients, peripheral or coronary atherosc lerosis (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 ca loric intake, the patients had hypertriglyceridemia (mean [+/-SD] trig lyceride level, 2621+/-1112 mg per deciliter [29.59+/-12.55 mmol per l iter]), low plasma levels of high-density lipoprotein cholesterol (17/-7 mg per deciliter [0.43+/-0.18 mmol per liter]), and very low level s of LDL cholesterol (28+/-16 mg per deciliter [0.72+/-0.41 mmol per l iter]). Three patients had one risk factor for atherosclerosis, wherea s in one male patient, heavy smoking and diabetes were associated with an accelerated course of the disease. Conclusions Premature atheroscl erosis 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, Massac husetts Medical Society.