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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:1400-1406.)
© 1997 American Heart Association, Inc.

Articles

Therapeutic Response to Medium-Chain Triglycerides and -3 Fatty Acids in a Patient With the Familial Chylomicronemia Syndrome

Mustapha Rouis; Klaus A. Dugi; Lorenzo Previato; Amy P. Patterson; John D. Brunzell; H. Bryan Brewer; ; Silvia Santamarina-Fojo

From the Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md (M.R., K.A.D., L.P., A.P.P., H.B.B., S.S.-F.), and the Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, University of Washington, Seattle (J.D.B.).

Correspondence to Silvia Santamarina-Fojo, Molecular Disease Branch, National Institutes of Health, NHLBI, Bldg 10, Room 7N115, 10 Center Dr, MSC 1666, Bethesda, MD 20892-1666. E-mail silvia{at}mdb.nhlbi.nih.gov

Abstract 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 -3 fatty acid (-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 -3-FA, plasma triglyceride increased to >2000 mg/dL. Northern blotting revealed both 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 familial chylomicronemia syndrome who manifests an unusually beneficial therapeutic response to MCT oil and -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.

Key Words: familial chylomicronemia • lipoprotein lipase • medium-chain triglyceride • -3 fatty acids • hypertriglyceridemia

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