Lipoprotein disorders

Lipoprotein Disorders Microchapters
Patient Information
Overview
Causes
Classification Hyperlipoproteinemia Hypolipoproteinemia
Treatment

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 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 This approach is considered outdated for a number of reasons.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 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. 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. 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.

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

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	APOA5	VLDL, CHYLOMICRONS
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