Lipoprotein disorders classification
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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Lipoprotein Disorders Microchapters |
Overview
Hyperlipidemias are classified according to the Fredrickson classification which is based on the pattern of lipoproteins on electrophoresis or ultracentrifugation.[1] It was later adopted by the World Health Organization (WHO). It does not directly account for HDL, and it does not distinguish among the different genes that may be partially responsible for some of these conditions. It remains a popular system of classification, but is considered dated by many.
Classification
| Hyperlipoproteinemia | Synonyms | Problems | Labs description | Treatment |
|---|---|---|---|---|
| Type I | Buerger-Gruetz syndrome, Primary hyperlipoproteinaemia, or Familial hyperchylomicronemia | Decreased lipoprotein lipase (LPL) or altered ApoC2 | Elevated Chylomicrons | Diet Control |
| Type IIa | Polygenic hypercholesterolaemia or Familial hypercholesterolemia | LDL receptor deficiency | Elevated LDL only | Bile Acid Sequestrants, Statins, Niacin |
| Type IIb | Combined hyperlipidemia | Decreased LDL receptor and Increased ApoB | Elevated LDL and VLDL and Triglycerides | Statins, Niacin, Gemfibrozil |
| Type III | Familial Dysbetalipoproteinemia | Defect in ApoE synthesis | Increased IDL | Drug of choice: Gemfibrozil |
| Type IV | Endogenous Hyperlipemia | Increased VLDL production and Decreased elimination | Increased VLDL | Drug of choice: Niacin |
| Type V | Familial Hypertriglyceridemia | Increased VLDL production and Decreased LPL | Increased VLDL and Chylomicrons | Niacin, Gemfibrozil |
Hyperlipoproteinemia type I
This very rare form (also known as Buerger-Gruetz syndrome, primary hyperlipoproteinaemia, or familial hyperchylomicronemia) is due to a deficiency of lipoprotein lipase (LPL) or altered apolipoprotein C2, resulting in elevated chylomicrons, the particles that transfer fatty acids from the digestive tract to the liver. Lipoprotein lipase is also responsible for the initial breakdown of endogenously made triacylglycerides in the form of very low density lipoprotein (VLDL). As such, one would expect a defect in LPL to also result in elevated VLDL. Its prevalence is 0.1% of the population.
Hyperlipoproteinemia type II
Hyperlipoproteinemia type II, by far the most common form, is further classified into type IIa and type IIb, depending mainly on whether there is elevation in the triglyceride level in addition to LDL cholesterol.
Type IIa
This may be sporadic (due to dietary factors), polygenic, or truly familial as a result of a mutation either in the LDL receptor gene on chromosome 19 (0.2% of the population) or the ApoB gene (0.2%). The familial form is characterized by tendon xanthoma, xanthelasma and premature cardiovascular disease.
Type IIb
The high VLDL levels are due to overproduction of substrates, including triglycerides, acetyl CoA, and an increase in B-100 synthesis. They may also be caused by the decreased clearance of LDL. Prevalence in the population is 10%.
- Familial combined hyperlipoproteinemia (FCH)
- Secondary combined hyperlipoproteinemia (usually in the context of metabolic syndrome, for which it is a diagnostic criterion)
Treatment
While dietary modification is the initial approach, many patients require treatment with statins (HMG-CoA reductase inhibitors) to reduce cardiovascular risk. If the triglyceride level is markedly raised, fibrates may be preferable due to their beneficial effects. Combination treatment of statins and fibrates, while highly effective, causes a markedly increased risk of myopathy and rhabdomyolysis and is therefore only done under close supervision. Other agents commonly added to statins are ezetimibe, niacin and bile acid sequestrants. There is some evidence for benefit of plant sterol-containing products and ω3-fatty acids[2]
Hyperlipoproteinemia type III
This form is due to high chylomicrons and IDL (intermediate density lipoprotein). Also known as broad beta disease or dysbetalipoproteinemia, the most common cause for this form is the presence of ApoE E2/E2 genotype. It is due to cholesterol-rich VLDL (β-VLDL). Prevalence is 0.02% of the population.
Hyperlipoproteinemia type IV
This form is due to high triglycerides. It is also known as hypertriglyceridemia (or pure hypertriglyceridemia). According to the NCEP-ATPIII definition of high triglycerides (>200 mg/dl), prevalence is about 16% of adult population.[3]
Hyperlipoproteinemia type V
This type is very similar to type I, but with high VLDL in addition to chylomicrons.
It is also associated with glucose intolerance and hyperuricemia
Unclassified forms
Non-classified forms are extremely rare:
- Hypo-alpha lipoproteinemia
- Hypo-beta lipoproteinemia (prevalence 0.01-0.1%)
References
- ↑ Frederickson DS, Lee RS. A system for phenotyping hyperlipidemia. Circulation 1965;31:321-7. PMID 14262568.
- ↑ Thompson GR. Management of dyslipidaemia. Heart 2004;90:949-55. PMID 15253984.
- ↑ 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. Circulation 2002; 106; page 3240
External links
| Hyperlipoproteinemia | OMIM | GPnotebook | WebMD | Others |
|---|---|---|---|---|
| Type I | Online Mendelian Inheritance in Man (OMIM) 238600 | Template:GPnotebook | . | MeritCare |
| Type IIa | Online Mendelian Inheritance in Man (OMIM) 144400 | Template:GPnotebook | . | Merck |
| Type IIb | Template:GPnotebook | . | ||
| Type III | . | Template:GPnotebook | WebMD | Yahoo |
| Type IV | Online Mendelian Inheritance in Man (OMIM) 144600 | Template:GPnotebook | WebMD | Yahoo |
| Type V | Online Mendelian Inheritance in Man (OMIM) 144600 | Template:GPnotebook | . | . |