Lipoprotein disorders
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2], Hardik Patel, M.D., Tarek Nafee, M.D. [3], Prince Tano Djan, BSc, MBChB [4], Aravind Kuchkuntla, M.B.B.S[5], Usama Talib, BSc, MD [6], Shivani Chaparala M.B.B.S [7], Vishal Devarkonda, M.B.B.S[8]
Synonyms and keywords:
Overview
Overview
Lipoproteins are aggregates of proteins and lipids that facilitate the circulation of hydrophobic lipids in the body. Disorders of lipids and lipoproteins metabolism have important health consequences, primarily on the cardiovascular system; however, may also affect the cerebrovascular system as well as the gastrointestinal system. Lipoprotein disorders can be described as abnormalities in the level of the lipids, which include cholesterol and triglycerides, or as abnormalities in the levels of lipoproteins that include LDL, HDL, VLDL and chylomicrons.
Lipoprotein disorders (also referred to as Lipid disorders, or Dyslipidemias, or Dyslipoproteinemias) were first classified in 1967 into different phenotypes by Fredrickson according to the type of lipoproteins that are affected. This approach is considered outdated for a number of reasons. Firstly, Friedrickson’s classification failed to classify disorders of low lipids. Secondly, Fredrickson’s classification of hyperlipoproteinemias took into consideration the elevation in chylomicrons, LDL, VLDL but did not include abnormalities in HDL levels. Other classifications have been suggested, one of which is the National Cholesterol Education Program (NCEP) classification of lipoprotein disorders. NCEP classifies lipid disorders according to laboratory cut off points for the levels of total cholesterol, LDL-C and HDL.
Lipoprotein disorders must be initially classified broadly into hypolipidemias and hyperlipidemias corresponding to low or high lipid levels, respectively. Each of these broad categories may be further classified into primary (genetic) causes or secondary environmental causes (e.g. substance abuse, medication use, lifestyle habits, or underlying diseases, etc.). Secondary causes of lipid disorders are more common and thus must be ruled out before exploring the primary causes of dyslipidemia.
Primary dyslipidemias are generally consistent in the way they affect the lipoproteins. Hyperlipoproteinemias generally cause elevations in the affected lipids/lipoproteins and hypolipoproteinemias generally cause reductions in the affected lipids/lipoproteins. Secondary dyslipidemias, on the other hand, may cause elevations in some lipoproteins and reductions in others. An example of this is the lipid profile in patients with diabetes mellitus, which commonly reveals a dyslipidemic triad consisting of elevated LDL and triglycerides with a concurrent reduction in HDL.[1][2] In this case, diabetes mellitus and metabolic syndrome would be widely considered a hyperlipidemic disease due to the array of cardiovascular and cerebrovascular sequelae that arise consequent to the chronic hyperlipidemia associated with the disease.[2] This is to say that in cases of mixed (elevated and decreased) findings on the lipid profile, clinicians must evaluate the secondary causes of the dysipidemia and manage the affected lipoproteins accordingly.
Causes
Causes
For a complete list of causes of hyperlipoproteinemia click here.
For a complete list of causes of hypolipoproteinemia click here.
The table below summarizes is a list of primary lipoprotein disorders:
| Type of lipoprotein disorder | Genetic Lipoprotein Disorder | Gene Involved | Main Lipoprotein Involved |
|---|---|---|---|
| Hyperlipoproteinemias | Autosomal dominant hypercholesterolemia | PCSK9 | LDL |
| Autosomal recessive hypercholesterolemia | ARH | LDL | |
| Familial sitosterolemia | ABCG5 – ABCG8 | LDL | |
| Familial lipoprotein(a) hyperlipoproteinemia | Apo(a) | LDL | |
| Familial defective apo B100 | Apo B | LDL | |
| Hepatic lipase deficiency | HL | ||
| Lipoprotein lipase deficiency | LPL | Chylomicron | |
| Apo C-II deficiency | Apo C-II | Chylomicron | |
| Apo A-V deficiency | Apo A-V deficiency | Chylomicron | |
| Hypolipoproteinemias | Familial hypoalphalipoproteinemia | ||
| GPIHBP1 deficiency | GPIHBP1 | Chylomicron | |
| Apo A-I deficiency | Apo A-I | HDL | |
| CETP deficiency | CETP | HDL | |
| Niemann-Pick disease | SMPD1, NPC1 | HDL |
Classification
Classification
| Lipid disorders | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hypolipoproteinemia | Hyperlipoproteinemia | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Secondary | Primary | Secondary | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Low LDL | Low HDL | Anemia, Chronic inflammation, Chronic liver disease, Hyperthyroidism, Infection, Malabsorption, Malignancy, Criticial illness, More Causes… | Alcohol, Diabetes, Drugs, Liver disease, Obesity, Renal disease, Smoking, Hypothyroidism More Causes… | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abetalipoproteinemia Hypobetalipoproteinemia PCSK9 deficiency Chylomicron retention disease Familial combined hypolipidemia | LCAT deficiency, Apolipoprotein 1 deficiency, Familial hypoalphalipoproteinemia, Tangier disease, FISH eye disease, Familial combined hypolipidemia | Type I: Familial hyperchylomicronemia | Type II | Type III: Dysbetalipoproteinemia | Type IV: Primary hypertriglyceridemia | Type V: Mixed hyperlipoproteinemia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Type A: Familial hypercholesterolemia | Type B: Familial combined hyperlipidemia | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Lipoprotein disorders can be 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 outdated by many.
Classification
There are several ways in which lipoprotein abnormalities are classified. Lipoprotein disorders can be classified according to:
- The pattern of change in the lipoprotein levels, described as hyperlipidemia (increase in lipid levels) and hypolipidemia (decrease in lipid levels): However, this classification is problematic because the lipids and lipoproteins levels in some situation can be elevated in some types of lipoproteins and lipids and decreased in others.
- Phenotype, or the specific type of lipid that is increased, as classified by Fredrickson: This classification is problematic because it does not include abnormalities in the level of HDL.
- Etiology, as primary (genetic) or secondary to another condition: This classification can be problematic, because most conditions involve the intersection of genetics and lifestyle issues. However, there are a few well defined genetic conditions that are usually easy to identify.
- Levels of measured lipids (cholesterol and triglycerides), described as hypercholesterolemia and hypocholesterolemia or hypertriglyceridimia and hypotriglyceridemia: This distinction is not specific because it does not reflect the specific lipoprotein(s) that are abnormally high or low.
Fredrickson Classification of Hyperlipoproteinemia
| Hyperlipoproteinemia/Hyperlipidemia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Type I: Familial hyperchylomicronemia | Type II | Type III: Dysbetalipoproteinemia | Type IV: Primary hypertriglyceridemia | Type V: Mixed hyperlipoproteinemia | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Type A: Familial hypercholesterolemia | Type B: Familial combined hyperlipidemia | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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, 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 |
Unclassified forms
Non-classified forms are extremely rare:
- Hypo-alpha lipoproteinemia
- Hypo-beta lipoproteinemia (prevalence 0.01-0.1%)
Classification According to Etiology
| Lipoprotein/Lipid disorders | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary (Genetic) | Secondary | ||||||||||||||||||||||||||||||||||||||||||||||||||
| LDL | Chylomicron Remnants | Lipoproteins Rich in Triglyceride (Chylomicrons, VLDL, IDL) | HDL | Multiple lipoproteins | Alcohol Diabetes Drugs Liver disease Obesity Renal disease Smoking Thyroid | ||||||||||||||||||||||||||||||||||||||||||||||
| High LDL: -Familial hypercholesterolemia -Familial defective apo B 100 -Autosomal dominant hypercholesterolemia (PCSK9) -Autosomal recessive hypercholesterolemia -Familial sistosterolemia -Familial lipoprotein a lipoproteinemia Low LDL: -Abetalipoproteinemia -Hypobetalipoproteinemia -PCSK 9 deficiency | -Deficiency in hepatic lipase -Type III dysbetalipoproteinemia | -Deficiency in lipoprotein lipase -Deficiency in Apo C-II -Deficiency in Apo A-V -Familial combined hyperlipidemia -Familial hypertriglyceridemia – Chylomicron retention disease | High LDL: -Cholesteryl ester transferase protein deficiency Low HDL: -Deficiency in Apo A-I -Deficiency in lecithin cholesterol acyltransferase (LCAT) -Familial hypoalphalipoproteinemia -Nieman-Pick disease -Tangier disease | – Familial combined hypolipidemia (ANGPTL3) | |||||||||||||||||||||||||||||||||||||||||||||||
Classification According to Laboratory Results
| Lipid Laboratory Tests | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Total cholesterol | LDL-C | HDL-C | Triglycerides | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| High total cholesterol | Low total cholesterol | High LDL | Low LDL | High HDL | Low HDL | High triglyceride | Low triglyceride | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
External links
References
- ↑ Frederickson DS, Lee RS. A system for phenotyping hyperlipidemia. Circulation 1965;31:321-7. PMID 14262568.
References
References
- ↑ Musunuru K (2010). “Atherogenic dyslipidemia: cardiovascular risk and dietary intervention”. Lipids. 45 (10): 907–14. doi:10.1007/s11745-010-3408-1. PMC 2950930. PMID 20524075.
- ↑ 2.0 2.1 Nesto RW (2005). “Beyond low-density lipoprotein: addressing the atherogenic lipid triad in type 2 diabetes mellitus and the metabolic syndrome”. Am J Cardiovasc Drugs. 5 (6): 379–87. PMID 16259526.
Looking for the patient version?
© 2026 MyEClinic – IFTM Institut für Telematik in der Medizin GmbH