Lipoprotein disorders
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Lipoprotein Disorders Microchapters |
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]
Overview
Lipoproteins, which are aggregates of proteins and lipids, allow the circulation of hydrophobic lipids in the body. Disorders of lipids and lipoproteins metabolism have important health consequences, mainly on the cardiovascular 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 have been initially classified in 1967 into different phenotypes by Fredrickson according to the type of lipoproteins that accumulate. However; 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 can be classified according to different criteria. First of all, lipoprotein disorders can be classified as primary disorders resulting from genetic mutations and secondary to other diseases. Another way of classifying lipoprotein disorders is as hypolipidemia (or hypolipoproteinemia) and hyperlipidemia (hyperlipoproteinemia) where the lipoprotein levels are decreased and increased respectively. However, the latter classification is not precise and creates some ambiguity, because some people can be labeled as having hyperlipidemia but have simultaneously high level of some lipoproteins and low levels of other lipoproteins depending on the underlying pathophysiology. Hence, a better term to describe the constellation of abnormal lipid profiles is "disorders of lipoproteins", or dyslipoproteinemia or dyslipidemia.
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 | Alcohol, Diabetes, Drugs Liver disease, Obesity Renal disease Smoking, Hypothyroidism | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Causes
For a complete list of causes of hyperlipoproteinemia click here.
For a complete list of causes of hypolipoproteinemia click here.
Genetics
Common Primary Lipoprotein Disorders
Shown below is a table summarizing the primary lipoprotein disorders along with the the gene and main lipoprotein involved in each disease:
| Type of lipoprotein disorder | Genetic Lipoprotein Disorder | Gene Involved | Main Lipoprotein Involved |
|---|---|---|---|
| Hyperlipoproteinemias | Familial hyperchylomicronemia Type I | ||
| Familial hypercholesterolemia Type IIA | LDL-R | LDL | |
| Familial combined hyperlipidemia Type IIB | Multiple genes | ||
| Dysbetalipoproteinemia type III | Apo E | ||
| Familial hypertriglyceridemia Type IV | Multiple genes | ||
| Mixed hyperlipoproteinemia Type V | |||
| Hypolipoproteinemias | Abetalipoproteinemia | MTP | LDL |
| Hypobetalipoproteinemia | Apo B | LDL | |
| Familial hypoalphalipoproteinemia | |||
| Tangier disease | ABCA1 | HDL | |
| Familial LCAT deficiency | LCAT | HDL | |
| PCSK9 deficiency | PCSK9 | HDL | |
| Chylomicron retention disease | SAR1B | Multiple |
Rare 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 |