Severe hypertriglyceridaemia (HTG) is recognised as the third most common cause of acute pancreatitis. While secondary causes of HTG such as excess alcohol, obesity and diabetes are well recognised, identification and treatment of primary genetic disorders such as lipoprotein lipase (LPL) deficiency remain a challenge. HTG secondary to such genetic disorders does not respond to established medical therapy, resulting in recurrent episodes of acute pancreatitis. A very low fat diet remains first-line therapy in the treatment of severe HTG secondary to LPL deficiency, and in resistant cases insulin, heparin and plasma apheresis are used with some success. Viral vector-delivered gene therapy is a novel treatment option that is currently being tested in patients with LPL deficiency with promising results.
Toskes PPHyperlipidemic pancreatitis. Gastroenterol Clin North Am1990;19:783-91.
2.
Gaudet D., de Wal J., Tremblay K. et al. Review of the clinical development of alipogene tiparvovec gene therapy for lipoprotein lipase deficiency. Atheroscler Suppl2010;11:55-60.
3.
Speck L.A case of lipidemia. Arch Verin Wissenschaftl Heilkunde1865; 1:232.
4.
Anderson F., Thompson SR, Clarke DL, Buccimazza I.Dyslipidemic pancreatitis clinical assessment and analysis of disease severity and outcomes. Pancreatology2009;9:252-7.
5.
Chang CC, Hsieh YY, Tsai HD et al. Acute pancreatitis in pregnancy. Zhonghua Yi Xue Za Zhi1998;61:85-92.
6.
Friedrickson DSAn international classification of hyperlipidemias and hyperlipoproteinemias. Ann Intern Med1971;75:471-2.
7.
Brunzell JD, Deeb SSFamilial lipoprotein lipase deficiency, Apo C-II deficiency and hepatic lipase deficiency. In: Scriven CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited disease. 8th edn. New York : McGraw-Hill, 2000, pp.2789-816.
8.
Goldberg IJ, Merkel M.Lipoprotien lipase: physiology, biochemistry, and molecular biology. Front Biosci2001;6:D388-405.
9.
Franssen R., Young SG, Peelman F. et al. Chylomicronemia with low post heparin lipoprotein lipase levels in the setting of GPIHBP1 defects. Circ Cardiovasc Genet2010;3:169-78.
10.
Pruneta-Deloche V., Marciuas C., Perrot L. et al. Combination of circulating antilipoprotein lipase (Anti-LPL) antibody and heterozygous S172fsX179 mutation of LPL gene leading to chronic hyperchylomicronemia. J Clin Endocrinol Metab2005;90:3995-8.
11.
Black DM, Sprecher DLDietary treatment and growth of hyperchylomicronemic children severely restricted in dietary fat. Am J Dis Child1993;147:60-2.
12.
Santamarina-Fojo S.The familial chylomicronemia syndrome. Endocrinol Metab Clin North Am1998;27:551-67.
13.
Havel RJPathogenesis, differentiation and management of hypertriglyceridemia. Adv Intern Med1969;15:117-45.
14.
Saharia P., Margolis S., Zuidema MD, Cameron JLAcute pancreatitis with hyperlipidemia: studies with an isolated perfused canine pancreas. Surgery1977;82:60-7.
15.
Kimura W., Mössner J.Role of hypertriglyceridemia in the pathogenesis of experimental acute pancreatitis in rats. Int J Pancreatol1996;20: 177-84.
16.
Ong JM, Kirchgessner TG, Schotz MC et al. Insulin increases the synthetic rate and messenger RNA level of lipoprotein lipase in isolated rat adipocytes. J Biol Chem1988;253:12,933-8.
17.
Jabbar MA, Zuhri-Yafi MI, Larrea J.Insulin therapy for a non-diabetic patient with severe hypertriglyceridemia . J Am Coll Nutr1998;17: 458-61.
18.
Mikhail N., Trivedi K., Page C. et al. Treatment of severe hypertriglyceridemia in nondiabetic patients with insulin. Am J Emerg Med2005;23:415-17.
19.
Tamez-Perez HE, Saenz-Gallegos R., Hernandez-Rodriguez K. et al. Insulin therapy in patients with severe hypertriglyceridemia. Rev Med Inst Mex Seguro Soc2006;44:235-7.
20.
Korn EDClearing factor, a heparin-activated lipoprotein lipase. I. Isolation and characterization of the enzyme from normal rat heart. J Biol Chem1955;215:1-14.
21.
Loo CC, Tan JYDecreasing the plasma triglyceride level in hypertriglyceridemia-induced pancreatitis in pregnancy: a case report. Am J Obstet Gynecol2002;187:241-2.
22.
Sharma P., Lim S., James D. et al. Pancreatitis may occur with a normal amylase concentration in hypertriglyceridaemia . BMJ1996;313:1265.
23.
Sleth JC, Lafforgue E., Servais R. et al. A case of hypertriglycideremiainduced pancreatitis in pregnancy: value of heparin. Ann Fr Anesth Reanim2004 ;23:835-7.
24.
Nasstrom B. , Olivecrona G., Olivecrona T. et al. Lipoprotein lipase during continuous heparin infusion: tissue stores become partially depleted. J Lab Clin Med2001;138:206-13.
25.
Weintraub M. , Rassin T., Eisenberg S. et al. Continuous intravenous heparin administration in humans causes a decrease in serum lipolytic activity and accumulation of chylomicrons in circulation. J Lipid Res1994 ;35:229-38.
26.
Betteridge DJ, Bakowski M., Taylor KG et al. Treatment of severe diabetic hypertriglyceridaemia by plasma exchange. Lancet1978;i:1368.
27.
Tsuang W., Navaneethan U., Ruiz L. et al. Hypertriglyceridemic pancreatitis: presentation and management . Am J Gastroenterol2009;104:984-91.
28.
Connor WEThe dietary treatment of hypertriglyceridemia. Med Clin North Am1982;66:485.
29.
Staels B., Dallongeville J., Auwerx J. et al. Mechanism of action of fibrates on lipid and lipoprotein metabolism . Circulation1998;98: 2088-93.
30.
Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): final report. NIH publication no. 02-5215. Bethesda, MD: National Heart, Lung, and Blood Institute , September 2002.
31.
Harris WS, Ginsberg HN, Arunakul N. et al. Safety and efficacy of Omacor in severe hypertriglyceridemia. J Cardiovasc Risk1997;4: 385-91.
32.
Healy AP, Sharer N., Rameh B. et al. Prevention of recurrent pancreatitis in familial lipoprotein lipase deficiency with high-dose antioxidant therapy. J Clin Endocrinol Metab1999;84:1203-5.
33.
Piolot A., Nadler F., Cavallero E. et al. Prevention of recurrent acute pancreatitis in patients with severe hypertriglyceridemia: value of regular plasmapheresis. Pancreas1996;13:96-9.
34.
Rip J., van Dijk KW, Sierts JA et al. AAV1-LPL(S447X) gene therapy reduces hypertriglyceridemia in apoE2 knock in mice. Biochim Biophys Acta2006;1761:1163-8.
35.
Wittrup HH, Tybjaerg-Hansen A., Nordestgaard BGLipoprotein lipase mutations, plasma lipids and lipoproteins, and risk of ischemic heart disease. A meta-analysis. Circulation1999;99:2901-7.
36.
Ak K., Isbir S., Tekeli A. et al. Presence of lipoprotein lipase S447X stop codon affects the magnitude of interleukin 8 release after cardiac surgery with cardiopulmonary bypass . J Thorac Cardiovasc Surg2007;134:477-83.
37.
Desoye G., Schweditsch MO, Pfeiffer KP et al. Correlation of hormones with lipid and lipoprotein levels during normal pregnancy and post partum. J Clin Endocrinol Metab1987;64:704-12.
38.
Lain KY, Catalano PMMetabolic changes in pregnancy. Clin Obstet Gynecol2007;50:938-48.
39.
Alvarez JJ, Montelongo A., Iglesias A. et al. Longitudinal study on lipoprotein profile, high density lipoprotein subclass, and post heparin lipases during gestation in women. J Lipid Res1996;37:299-308.
40.
Basaran A.Pregnancy-induced hyperlipoproteinemia: review of the literature. Reprod Sci2009;16:431-7.
41.
Al-Shali K. , Wang J., Fellows F. et al. Successful pregnancy outcome in a patient with severe chylomicronemia due to compound heterozygosity for mutant lipoprotein lipase. Clin Biochem2002;35:125-30.
42.
Tsai EC, Brown JA, Veldee MY et al. Potential of essential fatty acid deficiency with extremely low fat diet in lipoprotein lipase deficiency during pregnancy: a case report . BMC Pregnancy Childbirth2004; 4:27.
43.
Benlian P., De Gennes JL, Foubert L. et al. Premature atherosclerosis in patients with familial chylomicronemia caused by mutations in the lipoprotein lipase gene. N Engl J Med1996;335:848-54.
44.
Neil HA, Cooper J., Betteridge DJ et al. All-cause and cardiovascular mortality in treated patients with severe hypertriglyceridaemia: a long-term prospective registry study. Atherosclerosis2010;211:618-23.
