Lipoprotein lipase deficiency, familial

Familial lipoprotein lipase deficiency is characterized by a massive accumulation of chylomicrons and a corresponding increase in plasma triglycerides or a type I lipoprotein pattern. Presenting manifestations include repeated attacks of pancreatitis and abdominal pain, eruptive cutaneous xanthomatosis, and hepatosplenomegaly beginning in childhood. Symptom severity is proportional to dietary fat intake, and consequently to the elevation of chylomicrons. Accelerated atherosclerosis is not associated with this disease. 

Primary chylomicronemia (familial lipoprotein lipase or cofactor deficiency) Chylomicrons, VLDL increased Dietary management (niacin, fibrate) Niacin plus fibrate... 

Breckenridge WC, Little JA, Alaupovic P, Wang CS, Kuksis A, Kakis G, Lindgren F, Gardiner G (1982) Lipoprotein abnormalities associated with a familial deficiency of hepatic lipase. Atherosclerosis 45 161-179... 

Apo C-ll activates lipoprotein lipase, which degrades the chylomicron s triacylglycerol to fatty acids and glycerol. The fatty acids that are released are stored (in the adipose) or used for energy (by the muscle). The glycerol is metabolized by the liver. Patients with a deficiency of lipoprotein lipase or apo C-ll show a dramatic accumulation of chylomicrons in the plasma (type 1 hyperlipoproteinemia, familial lipoprotein lipase deficiency, or hypertriacylglycerolemia)... 

Lipoprotein lipase (EC 3.1.1.34) is an enzyme or group of enzymes which catalyze the hydrolysis of the 1(3) ester bond(s) of triacylglycerols and the 1 ester bond of phospholipids. The enzyme plays a central role in lipoprotein metabolism, being responsible in particular for the hydrolysis of chylomicron and VLDL triglycerides and the formation of remnant particles from these lipoproteins. There have been reviews of this enzyme [e.g., (N9, Ql)] and lipoprotein lipase will not be discussed in detail in this review. Familial lipoprotein lipase deficiency and related disorders of chylomicron metabolism have also been reviewed (B58, N8) and will not be discussed in detail. 

N8. Nikkila, E. A., Familial lipoprotein lipase deficiency and related disorders of chylomicron metabolism. In The Metabolic Basis of Inherited Disease 0. B. Stanbury, J. B. Wyngaarden, D. S. Fredrickson, J. L. Goldstein, and M. S. Brown, eds.), 5th Ed., pp. 622-642. McGraw-Hill, New York, 1983. 

A. Familial lipoprotein lipase deficiency (Type I lipoprotein pattern on electrophoresis). Serum triglycerides become elevated with particular elevation of chylomicrons. Tliere are xanthomas, rather than atherosclerosis. Pancreatitis may result from the action of pancreatic lipase on these elevated chylomicrons, with resultant excess triglyceride breakdown in the pancreas, pancreatic injury, and release of more pancreatic lipase. (Note that the body contains different kinds of lipases. There is a pancreatic lipase, which is a digestive enzyme a lipoprotein lipase, which is an extracellular enzyme that breaks down plasma triglycerides, thereby enabling fatty acids to enter cells and an intracellular lipase that breaks down stored triglycerides). 

A control and two patients with hyperlipidemia are studied after an overnight fast. Their plasma lipoprotein electrophoresis patterns are shown below, the control being in the middle lane. One of the patients has a pattern typical of type I lipoprotein lipase deficiency, and the other of type Ila familial hypercholesterolemia. Which of the bands observed in the electrophoretic gel patterns represents a lipoprotein fraction that is abnormally abundant after fasting and that is most enriched in triacylglycerides ... 

Brunzell ID, Deeb SS. Familial lipoprotein lipase deficiency, apo C-II deficiency, and hepatic lipase deficiency. In Scriver CR, Beaudet AL, Sly WS, et al., eds. The Metabolic and Molecular Bases of Inherited Disease, 8th ed. New York McGraw-Hill, 2001. 

I Familial lipoprotein lipase deficiency Increased chylomicrons decreased HDL levels Absence of certain apoproteins... 

Type I hyperlipoproteinaemia, known also as familial exogenous hyperlipaemia and familial hyperchylomicronaemia, is a rare recessive condition characterized by lipoprotein lipase deficiency with consequentially elevated plasma triacylglycerol concentrations. Pancreatitis rather than accelerated atherosclerosis is usually the immediate cause of death in these patients. 

The classification of hyperUpidaemias is confusing as there are two means of classification - the Fredrickson based on the pattern of plasma lipoproteins in each condition, and the Goldstein based on the underlying enzyme defects. Type I hyperlipidaemia (Fredrickson) is a lipoprotein lipase or apolipoprotein-C2 deficiency. It leads to massive Hpid deposition and presents in childhood. Type Da hyperlipidaemia (familial hypercholesterolaemia) is a severe illness, not to be confused with common hypercholesterolaemia. Familial hypercholesterolaemia presents in childhood with deposits of cholesterol in the skin and ischaemic heart disease in adolescence. 

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