Type I hyperlipoproteinemia

Treatment of type I hyperlipoproteinemia is directed toward reduction of chylomicrons derived from dietary fat with the subsequent reduction in plasma triglycerides. Total daily fat intake should be no more than 10 to 25 g/day, or approximately 15% of total calories. Secondary causes of hypertriglyceridemia should be excluded, and, if present, the underlying disorder should be treated appropriately. 

The answer is a. (Hardman, pp 875-898.) In type I hyperlipoproteinemia, drugs that reduce levels of lipoproteins are not useful, but reduction of dietary sources of fat may help. Cholesterol levels are usually normal, but triglycerides are elevated. Maintenance of ideal body weight is recommended in all types of hyperlipidemia. Clofibrate effectively reduces the levels of VLDLs that are characteristic of types 111, IV, and V hyperlipoproteinemia administration of cholestyramine resin and lovastatin in conjunction with a low-cholesterol diet is regarded as effective therapy for type 11a, or primary, hyperbetalipoproteinemia, except in the homozygous familial form. 

Lipoprotein lipase (LPL) deficiency is inherited as an autosomal recessive disorder. Hyperchylomicronemia is present from birth. Upon fat ingestion, triacylglycerol levels may rise to 5000-10,000 mg/dL. Chylomicron levels are greatly elevated but not the VLDL levels (type I hyperlipoproteinemia). Type I hyperlipoproteinemia can also be... 

Hyperlipoproteinemias Famiiiai iipoprotein iipase deficiency (type i) Hypertriacylglycerolemia due to deficiency of LPL, abnormal LPL, or apo C-ll deficiency causing inactive LPL. Slow clearance of chylomicrons and VLDL. Low levels of LDL and HDL. No increased risk of coronary disease. 

Type V hyperlipoproteinemia requires stringent restriction of dietary fat intake. Drug therapy with fibrates or niacin is indicated if the response to diet alone is inadequate. Medium-chain triglycerides, which are absorbed without chylomicron formation, may be used as a dietary supplement for caloric intake if needed for both types I and V. 

Fate of the remaining chylomicron components After most of tt triacylglycerol has been removed, the chylomicron remnan (which contain cholesteryl esters, phospholipids, apolipoprotein and some triacylglycerol) bind to receptors on the liver (seej 228) and are then endocytosed. The remnants are the hydrolyzed to their component parts. Cholesterol and the nitrogf nous bases of phopholipids (for example, choline) can be req cled by the body. [Note If removal of chylomicron remnants by th liver is defective, they accumulate in the plasma. This is seen i type III hyperlipoproteinemia (also called familial dysbetalipopro teinemia, see p. 229). 

The isoforms of apoE were first clearly demonstrated by Utermann et al., who showed on one-dimensional isoelectric focusing of VLDL apolipoproteins that there were four major isoforms of apoE (U3— U5). These were named, from acidic to basic, apoE-1, apoE-2, apoE-3, and apoE-4. Patients with Type I1 hyperlipoproteinemia (dysbetalipoproteinemia) were, in virtually all cases, deficient in apoE-3 (U3-U6). Only 27% of subjects had apoeE-4, but this band was not associated with any particular abnormality. However, individuals deficient in apoE-3 were also deficient in apoE-4 (U6). Utermann suggested that the genetic pattern of apoE isoforms could be explained if there was a single genetic locus for apoE which could produce three apoE phenotypes, i.e., apoE-N (normal), apoE-D (deficient, associated particularly with the Type III disorder), and apoE-ND (U4, U6). 

While practically all subjects with Type III hyperlipoproteinemia appear to be homozygous for apoE-2 (i.e., to have the E-2IE-2 genotype), most subjects who are homozygotes for apoE-2 do not develop Type III hyperlipoproteinemia. Indeed, about 1% of the population is an E-2/E-2 homo-... 

Type I lipoproteinemia is generally caused by the inability of the organism to clear chylomicrons. The problem may be defective ApoC-II or a defective lipoprotein lipase. Very often, chylomicron clearance may be affected by injection of heparin, which apparently releases hepatic lipase from the liver into the circulation. ApoE disorders may be associated with type III lipoproteinemia, in which clearance of IDL is impeded. Increases in circulatory LDL are usually caused by a decrease in tissue receptors specific for ApoB-100. An extreme case of type Ha hyperlipoproteinemia is familial hypercholesterolemia, in which serum cholesterol levels may be as high as 1000 mg/dL and the subjects may die in adolescence from cardiovascular disease. There is total absence of ApoB-100 receptors. Mild type Ila and lib lipoproteinemias are the most commonly occurring primary lipoproteinemias in the general population. 

Type 1 delodirtase, 734-735, 826,827 Type I diabetes, see insulin-dependent diabetes mellitus Type II deiodinase, 735, 826, 827 Type II diabetes, see Non-insulin-dependent diabetes mellitus Type fll deiodinase, 735,826,827 Type HI hyperlipoproteinemia, 3S Tyrosine... 

Type II hyperlipoproteinemia has been divided inlutyrc I la and Ilb. Type I la is characterized by elevated levels LDL (j3-lipoproteins) and nomral levels of triglyceiiilr This subtype disorder is very common and may be ciusx by disturbed catabolism of LDL. Type Ilb differs ffomiyp lla. in that this hyperlipidemia has elevated VLDL Mdietary restrictions on eholcsteml and. saturated fuLs Tlii type of hyperlipoproteinemia responds to some fomi i ... 

Clofibrate is the drug of choice in the treatment of type III hyperlipoproteinemias and may also be useful, to a lesser tent. in types lib and IV hyperlipoproteinemias. The drug is not effective in types I and Ila. 

IVicofrn/c Acid. Nicotinic acid. 3-pyridinccarboxylic Kid (Niacin), is effective in the treatment of ali types nf hyperlipoproteinemia except type I, at dnses abnve thnse given as a vitamin supplement. The drug reduces VLDL... 

Langer, T., Strober, W., and Levy, R. I. (1972). The metabolism of low density lipoprotein in familial type II hyperlipoproteinemia. J. Clitt. Invest. 51,1S28-1536. 

Ghiselh GC, Schaefer EJ, Gascon P, Brewer HB Jr (1981) Type III hyperlipoproteinemia associated with plasma apolipoprotein E deficiency. Science 214 1239-1241 Gualandri V, Franceschini G, Sirtori CR, Gianfranceschi G, Orsini GB, Cerrone A, Menotti A (1985) A-I Milano apoprotein. Identification of the complete kindred and evidence of a dominant genetic transmission. Am J Hum Genet 37 1083-1097... 

They are useful only in hyperlipoproteinemias involving elevated levels of LDL i.e. type Ila, lib and V. They are basic ion exchange resins. They are neither digested nor absorbed in the gut. They bind bile acids in intestine and interrupt their entero-hepatic circulation, leading to increased faecal excretion of bile salts and cholesterol. There is increased hepatic conversion of choles-terol to bile acids. More LDL receptors are expressed on liver cells leading to increased clearance of IDL, LDL and indirectly of VLDL. 

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