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, 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

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

Type A

Type B

Type C

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