Lipoprotein disorders causes: Difference between revisions
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==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]] | |||
| Decreased [[lipoprotein lipase]] (LPL) | |||
|rowspan=3| [[Chylomicrons]] | |||
|rowspan=3| Abdominal pain (from [[pancreatitis]]), [[lipemia retinalis]], eruptive skin [[xanthoma]]s, [[hepatosplenomegaly]] | |||
|rowspan=3| Diet control | |||
|rowspan=3| Creamy top layer | |||
|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> | |||
|- | |||
! [[hyperlipoproteinemia type Ib|b]] | |||
| {{OMIM2|207750}} | |||
| [[Familial apoprotein CII deficiency]] | |||
| Altered [[apolipoprotein C2|ApoC2]] | |||
|- | |||
! [[Hyperlipoproteinemia type Ic|c]] | |||
| {{OMIM2|118830}} | |||
| | |||
| [[Lipoprotein lipase|LPL]] inhibitor in blood | |||
|- | |||
!rowspan=2| Type II | |||
! a | |||
| {{OMIM2|143890}} | |||
| ''[[Familial hypercholesterolemia]]'' | |||
| [[LDL receptor]] deficiency | |||
| [[LDL]] | |||
| [[Xanthelasma]], [[arcus senilis]], tendon [[xanthoma]]s | |||
| [[Bile acid sequestrant]]s, [[statin]]s, [[niacin]] | |||
| Clear | |||
| 1 in 500 for heterozygotes | |||
|- | |||
! b | |||
| {{OMIM2|144250}} | |||
| ''Familial [[combined hyperlipidemia]]'' | |||
| 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>]] | |||
====Hyperlipoproteinemia type I==== | ====Hyperlipoproteinemia type I==== | ||
* | {{anchor|type I}} | ||
Type I hyperlipoproteinemia exists in several forms: | |||
*[[Lipoprotein lipase deficiency|Lipoprotein lipase deficiency (Type Ia)]], due to a deficiency of [[lipoprotein lipase]] (LPL) or altered [[apolipoprotein C2]], resulting in elevated [[chylomicron]]s, the particles that transfer fatty acids from the [[digestive tract]] to the [[liver]]. | |||
*Familial apoprotein CII deficiency (Type Ib),<ref>[http://omim.org/entry/207750 OMIM entry 207750] last updated 02/10/2009</ref><ref>{{cite pmid|227429}}</ref> a condition caused by a lack of [[lipoprotein lipase]] activator.<ref name="Andrews">{{cite book |author=James, William D.; Berger, Timothy G.; et al. |title=Andrews' Diseases of the Skin: clinical Dermatology |publisher=Saunders Elsevier |location= |year=2006 |pages= |isbn=0-7216-2921-0 |oclc= |doi= |accessdate=}}</ref>{{rp|533}} | |||
*Chylomicronemia due to circulating inhibitor of lipoprotein lipase (Type Ic)<ref>[http://omim.org/entry/118830 OMIM entry 118830] updated 03/18/2004</ref> | |||
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==== | ||
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. | |||
=====Type IIa===== | =====Type IIa===== | ||
{{main|Familial hypercholesterolemia}} | |||
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 [[apolipoprotein B|ApoB]] gene (0.2%). The familial form is characterized by [[Xanthoma|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===== | =====Type IIb===== | ||
*Familial combined hyperlipoproteinemia (FCH) | 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%. | ||
* | * Familial combined hyperlipoproteinemia (FCH) | ||
* | * [[Lysosomal acid lipase deficiency]], often called ([[Cholesteryl ester storage disease]]) | ||
* Secondary combined hyperlipoproteinemia (usually in the context of [[metabolic syndrome]], for which it is a diagnostic criterion) | |||
====Hyperlipoproteinemia type III==== | ====Hyperlipoproteinemia type III==== | ||
This form is due to high [[chylomicron]]s and IDL (intermediate density lipoprotein). Also known as ''broad beta disease'' or ''dysbetalipoproteinemia'', the most common cause for this form is the presence of [[Apolipoprotein E|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.<ref name=fung2011/> | |||
====Hyperlipoproteinemia type IV==== | ====Hyperlipoproteinemia type IV==== | ||
[[Familial hypertriglyceridemia]] is an autosomal dominant condition occurring in approximately 1% of the population.<ref name=Boman1975/> | |||
====Hyperlipoproteinemia type V==== | ====Hyperlipoproteinemia type V==== | ||
*Very similar to type I, but with high [[VLDL]] in addition to chylomicrons | *Very similar to type I, but with high [[VLDL]] in addition to chylomicrons |
Revision as of 20:49, 26 October 2012
Lipoprotein Disorders Microchapters |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]; Associate Editor(s)-in-Chief: Hardik Patel, M.D.
Overview
Hyperlipidemia can occur as either a primary event or secondary to some underlying disease. The primary hyperlipidemias include chylomicronemia, hypercholesterolemia, dysbetalipoproteinemia, hypertriglyceridemia, mixed hyperlipoproteinemia, and combined hyperlipoproteinemia. Other diseases, such as diabetes mellitus, pancreatitis, renal disease, and hypothyroidism, can cause the secondary form.
Causes
Hyperlipidemias may basically be classified as either familial (also called primary[1]) caused by specific genetic abnormalities, or acquired (also called secondary)[1] when resulting from another underlying disorder that leads to alterations in plasma lipid and lipoprotein metabolism.[1] 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 Fredrickson classification which is based on the pattern of lipoproteins on electrophoresis or ultracentrifugation.[2] 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 dated by manyTemplate:Who.
Hyperlipo- proteinemia |
OMIM | Synonyms | Defect | Increased lipoprotein | Main symptoms | Treatment | Serum appearance | Estimated prevalence | |
---|---|---|---|---|---|---|---|---|---|
Type I | a | 238600 | Buerger-Gruetz syndrome, or Familial hyperchylomicronemia | Decreased lipoprotein lipase (LPL) | Chylomicrons | Abdominal pain (from pancreatitis), lipemia retinalis, eruptive skin xanthomas, hepatosplenomegaly | Diet control | Creamy top layer | 1 in 1,000,000[3] |
b | 207750 | Familial apoprotein CII deficiency | Altered ApoC2 | ||||||
c | 118830 | LPL inhibitor in blood | |||||||
Type II | a | 143890 | Familial hypercholesterolemia | LDL receptor deficiency | LDL | Xanthelasma, arcus senilis, tendon xanthomas | Bile acid sequestrants, statins, niacin | Clear | 1 in 500 for heterozygotes |
b | 144250 | Familial combined hyperlipidemia | Decreased LDL receptor and increased ApoB | LDL and VLDL | Statins, niacin, fibrate | Clear | 1 in 100 | ||
Type III | 107741 | Familial dysbetalipoproteinemia | Defect in Apo E 2 synthesis | IDL | Tubo-Eruptive Xanthomas & Palmar Xanthomas | Fibrate, statins | Turbid | 1 in 10,000[4] | |
Type IV | 144600 | Familial hypertriglyceridemia | Increased VLDL production and Decreased elimination | VLDL | Can cause pancreatitis at high triglyceride levels | Fibrate, niacin, statins | Turbid | 1 in 100[5] | |
Type V | 144650 | Increased VLDL production and Decreased LPL | VLDL and Chylomicrons | Niacin, fibrate | Creamy top layer & turbid bottom |
Hyperlipoproteinemia type I
Type I hyperlipoproteinemia exists in several forms:
- Lipoprotein lipase deficiency (Type Ia), due to a deficiency of lipoprotein lipase (LPL) or altered apolipoprotein C2, resulting in elevated chylomicrons, the particles that transfer fatty acids from the digestive tract to the liver.
- Familial apoprotein CII deficiency (Type Ib),[7][8] a condition caused by a lack of lipoprotein lipase activator.[9]:533
- Chylomicronemia due to circulating inhibitor of lipoprotein lipase (Type Ic)[10]
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.
Type IIa
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%.
- Familial combined hyperlipoproteinemia (FCH)
- Lysosomal acid lipase deficiency, often called (Cholesteryl ester storage disease)
- 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.[4]
Hyperlipoproteinemia type IV
Familial hypertriglyceridemia is an autosomal dominant condition occurring in approximately 1% of the population.[5]
Hyperlipoproteinemia type V
- Very similar to type I, but with high VLDL in addition to chylomicrons
- Associated with glucose intolerance and hyperuricemia
Familial lecithin-cholesterol acyltransferase (LCAT) deficiency[11]
- Caused by mutations of the LCAT gene located on chromosome 16q22, which is passed on in an autosomal recessive fashion
- Associated with corneal opacities, hemolytic anaemia, and proteinuria
Secondary Hyperlipidemia
Secondary to some underlying "non-lipid" etiology
- Acromegaly
- Alcohol
- Chronic renal failure
- Cholestatic liver diseases[12]
- Cushing's syndrome
- Connective tissue disorders
- Dysglobulinemias (lupus, lymphoma, myeloma, Waldenström's macroglobulinemia)
- Glycogen storage disease, type I
- Diabetes mellitus, type 2 [13]
- Hypothyroidism[14]
- Hypopituitarism (ateliotic dwarfism)
- Lipodystrophy (congenital or acquired)
- Nephrotic syndrome
- Obesity[15]
- Pancreatitis
- Pregnancy
- Sepsis
- Stress
- Smoking[16]
- Drugs
- Oral estrogens
- Thiazide diuretics
- Beta blockers
- Atypical antipsychotic agents, such as clozapine[17] and olanzapine[18]
- Antiretroviral drugs used for HIV infection, in particular the protease inhibitors
- Bile acid binding resins
- Cimetidine
- Glucocorticoids
- Isotretinoin
Causes by Organ System
Causes in Alphabetical Order
References
- ↑ 1.0 1.1 1.2 Chait A, Brunzell JD (1990). "Acquired hyperlipidemia (secondary dyslipoproteinemias)". Endocrinol. Metab. Clin. North Am. 19 (2): 259–78. PMID 2192873. Unknown parameter
|month=
ignored (help) - ↑ Fredrickson, DS; Lees, RS (1965). "A system for phenotyping hyperlipoproteinemia" (PDF). Circulation. 31 (3): 321–7. doi:10.1161/01.CIR.31.3.321. PMID 14262568.
- ↑ 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."
- ↑ 4.0 4.1 Template:Cite doi
- ↑ 5.0 5.1 Boman H,Hazzard WR, AlbersJJ, et ah Frequency of monogenic forms of hyperlipidemia in a normal population. AmJ ttum Genet 27:19A,1975. [1]
- ↑ New Product Bulletin on Crestor® (rosuvastatin) [2]
- ↑ OMIM entry 207750 last updated 02/10/2009
- ↑ PMID 227429 (PMID 227429)
Citation will be completed automatically in a few minutes. Jump the queue or expand by hand - ↑ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.
- ↑ OMIM entry 118830 updated 03/18/2004
- ↑ McIntyre N (1988). "Familial LCAT deficiency and fish-eye disease". J Inherit Metab Dis. 11 Suppl 1: 45–56. PMID 3141686.
- ↑ Rosenson RS, Baker AL, Chow MJ, Hay RV (1990). "Hyperviscosity syndrome in a hypercholesterolemic patient with primary biliary cirrhosis". Gastroenterology. 98 (5 Pt 1): 1351–7. PMID 2323525.
- ↑ Zavaroni I, Dall'Aglio E, Alpi O, Bruschi F, Bonora E, Pezzarossa A; et al. (1985). "Evidence for an independent relationship between plasma insulin and concentration of high density lipoprotein cholesterol and triglyceride". Atherosclerosis. 55 (3): 259–66. PMID 3893447.
- ↑ O'Brien T, Dinneen SF, O'Brien PC, Palumbo PJ (1993). "Hyperlipidemia in patients with primary and secondary hypothyroidism". Mayo Clin Proc. 68 (9): 860–6. PMID 8371604.
- ↑ Hubert HB, Feinleib M, McNamara PM, Castelli WP (1983). "Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study". Circulation. 67 (5): 968–77. PMID 6219830.
- ↑ Facchini FS, Hollenbeck CB, Jeppesen J, Chen YD, Reaven GM (1992). "Insulin resistance and cigarette smoking". Lancet. 339 (8802): 1128–30. PMID 1349365.
- ↑ Henderson DC (2001). "Clozapine: diabetes mellitus, weight gain, and lipid abnormalities". J Clin Psychiatry. 62 Suppl 23: 39–44. PMID 11603884.
- ↑ Osser DN, Najarian DM, Dufresne RL (1999). "Olanzapine increases weight and serum triglyceride levels". J Clin Psychiatry. 60 (11): 767–70. PMID 10584766.