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 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 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.
Rouis
M
M
Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md. 20892-1666, USA.
Dugi
K A
KA
Previato
L
L
Patterson
A P
AP
Brunzell
J D
JD
Brewer
H B
HB
Santamarina-Fojo
S
S
D000273:Adipose Tissue / Q000201:enzymology; D002648:Child; D002914:Chylomicrons / Q000097:blood*; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008049:Lipase / Q000097:blood*; D008052:Lipid Metabolism, Inborn Errors / Q000178:diet therapy*; D008071:Lipoprotein Lipase / Q000097:blood / Q000235:genetics; D008099:Liver / Q000201:enzymology; D008264:Macrophages / Q000201:enzymology; D008297:Male; D010375:Pedigree; D012333:RNA, Messenger / Q000378:metabolism; D014280:Triglycerides / Q000627:therapeutic use*
D002914:Chylomicrons; D015525:Fatty Acids, Omega-3; D012333:RNA, Messenger; D014280:Triglycerides; D008049:Lipase; D008071:Lipoprotein Lipase