Hyperlipidemias are divided in primary and secondary subtypes. Primary hyperlipidemia is usually due to genetic causes (such as a mutation in a receptor protein)such as [[chylomicronemia]], [[hypercholesterolemia]], [[dysbetalipoproteinemia]], [[hypertriglyceridemia]], [[mixed hyperlipoproteinemia]], and [[combined hyperlipoproteinemia]], while secondary hyperlipidemia arises due to other underlying causes such as [[diabetes mellitus|diabetes]]. Lipid and lipoprotein abnormalities are common in the general population, and are regarded as a modifiable risk factor for [[cardiovascular disease]] due to their influence on [[atherosclerosis]]. In addition, some forms may predispose to [[acute pancreatitis]].
Hyperlipidemias are caused by primary and secondary causes. Primary hyperlipidemia is usually due to genetic causes (such as a mutation in a receptor protein)such as [[chylomicronemia]], [[hypercholesterolemia]], [[dysbetalipoproteinemia]], [[hypertriglyceridemia]], [[mixed hyperlipoproteinemia]], and [[combined hyperlipoproteinemia]], while secondary hyperlipidemia arises due to other underlying causes such as [[diabetes mellitus|diabetes]]. Lipid and lipoprotein abnormalities are common in the general population, and are regarded as a modifiable risk factor for [[cardiovascular disease]] due to their influence on [[atherosclerosis]]. In addition, some forms may predispose to [[acute pancreatitis]].
==Causes==
==Causes==
Hyperlipidemias may basically be classified as either familial (also called primary<ref name=Chait>{{cite journal |author=Chait A, Brunzell JD |title=Acquired hyperlipidemia (secondary dyslipoproteinemias) |journal=Endocrinol. Metab. Clin. North Am. |volume=19 |issue=2 |pages=259–78 |year=1990 |month=June |pmid=2192873 |doi= |url=}}</ref>) caused by specific genetic abnormalities, or acquired (also called secondary)<ref name=Chait/> when resulting from another underlying disorder that leads to alterations in plasma lipid and lipoprotein metabolism.<ref name=Chait/> Also, hyperlipidemia may be idiopathic, that is, without known cause.
Hyperlipidemias are also classified according to which types of lipids are elevated, that is [[hypercholesterolemia]], [[hypertriglyceridemia]] or both in [[combined hyperlipidemia]]. Elevated levels of [[Lipoprotein(a)]] may also be classified as a form of hyperlipidemia.
===Familial (primary)===
Familial hyperlipidemias are classified according to the '''[[Donald S. Fredrickson|Fredrickson]] classification''' which is based on the pattern of lipoproteins on [[electrophoresis]] or [[Ultracentrifuge|ultracentrifugation]].<ref>{{cite journal | last1 = Fredrickson | first1 = DS | last2 = Lees | first2 = RS | title = A system for phenotyping hyperlipoproteinemia | journal = Circulation | volume = 31 | pages = 321–7 | year = 1965 | pmid = 14262568 | url=http://circ.ahajournals.org/cgi/reprint/31/3/321 | format=PDF | issue=3 | doi = 10.1161/01.CIR.31.3.321}}</ref> It was later adopted by the [[World Health Organization]] (WHO). It does not directly account for [[High density lipoprotein|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{{who|date=June 2012}}.
{| class="wikitable" class="sortable wikitable"
|+ '''Fredrickson classification of Hyperlipidemias'''
|-
!colspan=2| Hyperlipo-<br>proteinemia
! [[OMIM]]
! Synonyms
! Defect
! Increased lipoprotein
! Main symptoms
! Treatment
! Serum appearance
! Estimated prevalence
|-
!rowspan=3| [[Type I hyperlipoproteinemia|Type I]]
! [[Hyperlipoproteinemia type Ia|a]]
| {{OMIM2|238600}}
| ''[[Buerger-Gruetz syndrome]]'', or ''[[Familial hyperchylomicronemia]]
|rowspan=3| 1 in 1,000,000<ref>[http://www.cags.org.ae/FMPro?-DB=ctga.fp5&-Format=ctga/ctga_detail.html&-RecID=34563&-Find Hyperlipoproteinemia, Type I] from Centre for Arab Genomic Studies. Retrieved July 2011. Citing: "About 1:1,000,000 people are affected with Hyperlipoproteinemia type I worldwide with a higher prevalence in some regions of Canada."</ref>
| Decreased [[LDL receptor]] and increased [[apolipoprotein B|ApoB]]
| [[LDL]] and [[VLDL]]
|
| [[Statin]]s, [[niacin]], [[fibrate]]
| Clear
| 1 in 100
|-
!colspan=2| Type III
| {{OMIM2|107741}}
| ''[[Familial dysbetalipoproteinemia]]''
| Defect in [[apolipoprotein E|Apo E 2]] synthesis
| [[Intermediate density lipoprotein|IDL]]
| Tubo-Eruptive Xanthomas & Palmar Xanthomas
| [[Fibrate]], [[statin]]s
| Turbid
| 1 in 10,000<ref name=fung2011>{{cite doi|10.1136/bcr.02.2011.3895}}</ref>
|-
!colspan=2| Type IV
| {{OMIM2|144600}}
| ''[[Familial hypertriglyceridemia]]''
| Increased [[VLDL]] production and Decreased elimination
| [[VLDL]]
|Can cause [[pancreatitis]] at high triglyceride levels
| [[Fibrate]], [[niacin]], [[statin]]s
| Turbid
| 1 in 100<ref name=Boman1975>Boman H,Hazzard WR, AlbersJJ, et ah Frequency of monogenic forms of hyperlipidemia in a normal population. AmJ ttum Genet 27:19A,1975. [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1762895/pdf/ajhg00439-0130.pdf]</ref>
|-
!colspan=2| [[#type V|Type V]]
| {{OMIM2|144650}}
|
| Increased [[VLDL]] production and Decreased [[Lipoprotein lipase|LPL]]
| [[VLDL]] and [[Chylomicrons]]
|
| [[Niacin]], [[fibrate]]
| Creamy top layer & turbid bottom
|
|}
[[File:Relative prevalence of familial hyperlipoproteinemias.png|thumb|center|Relative prevalence of familial forms of hyperlipoproteinemia<ref>New Product Bulletin on Crestor® (rosuvastatin) [http://www.pharmacist.com/AM/Template.cfm?Section=Home2&CONTENTID=14388&TEMPLATE=/CM/ContentDisplay.cfm]</ref>]]
Familial apoprotein CII deficiency (Type Ib),[1][2] a condition caused by a lack of lipoprotein lipase activator.[3]:533
Chylomicronemia due to circulating inhibitor of lipoprotein lipase (Type Ic)[4]
Type I hyperlipoproteinemia usually presents in childhood with eruptive xanthomata and abdominal colic. Complications include retinal vein occlusion, acute pancreatitis, steatosis and organomegaly, and lipaemia retinalis.
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.
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. The incidence of this disease is about 1 in 500 for heterozygotes, and 1 in 1,000,000 for homozygotes.
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%.
Secondary combined hyperlipoproteinemia (usually in the context of metabolic syndrome, for which it is a diagnostic criterion)
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). Its prevalence has been estimated to be approximately 1 in 10,000.[5]
↑James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN0-7216-2921-0.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)