Therapeutic response to medium-chain triglycerides and omega-3 fatty acids in a patient with the familial chylomicronemia syndrome

We have studied the underlying molecular defect in a patient presenting with recurrent pancreatitis, hypertriglyceridemia, and virtually undetectable postheparin plasma lipoprotein lipase (LPL) mass and activity, who normalized her triglycerides 3 to 6 months after initiation of either medium-chain triglyceride (MCT) oil or omega-3 fatty acid (omega-3-FA) therapy, After treatment, postheparin plasma LPL activity and mass ranged from 24% to 39% of normal and LPL specific activity was normal (1.0 nmol . ng(-1) . min(-1)). On discontinuation of MCT oil or omega 3-FA, plasma triglyceride increased to >2000 mg/dL. Northern blotting revealed bath normal size and abundance of LPL mRNA isolated from adipocytes as well as macrophages. Sequence analysis of the LPL gene, which included all 10 exons, Intron-exon splice junctions, and 1.7 kb of the 5'-flanking region, and of LPL cDNA failed to identify any mutations. Apoc-II activity and mass assays revealed the presence of normal levels of a fully functional cofactor as well as the absence of circulating plasma inhibitors of lipase function. In summary, we describe a unique patient presenting with classical features of the familia! chylomicronemia syndrome who manifests an unusually beneficial therapeutic response to MCT oil and omega-3-FA therapy. Unlike that in most patients with LPL deficiency, the chylomicronemia in this patient is not caused by a mutation in the structural LPL gene but possibly by a posttranscriptional defect. Thus, a subset of LPL-deficient patients with unique genetic defects respond to therapy by normalizing fasting plasma triglycerides; a therapeutic trial with MCT oil should be considered in all patients presenting with the familial chylomicronemia syndrome.