Lipoprotein disorders causes
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Lipoprotein Disorders Microchapters |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hardik Patel, M.D.; Hilda Mahmoudi M.D., M.P.H.[2]
Overview
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. 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
Common Causes
- High fat diet
Causes by Organ System
Causes in Alphabetical Order
Familial (Primary) Hyperlipidemia
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),[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 lipemia 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 200 in 100,000 for heterozygotes, and 0.1 in 100,000 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 10 in 100,000.
Hyperlipoproteinemia Type IV
Familial hypertriglyceridemia is an autosomal dominant condition occurring in approximately 1% of the population.
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[5]
- 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
- Cholestatic liver diseases[6]
- Chronic renal failure
- Connective tissue disorders
- Cushing's syndrome
- Diabetes mellitus, type 2 [7]
- Dysglobulinemias (lupus, lymphoma, myeloma, Waldenström's macroglobulinemia)
- Glycogen storage disease, type I
- Drugs
- Antiretroviral drugs used for HIV infection, in particular the protease inhibitors
- Atypical antipsychotic agents, such as clozapine[8] and olanzapine[9]
- Beta blockers
- Bile acid binding resins
- Cimetidine
- Glucocorticoids
- Isotretinoin
- Oral estrogens
- Thiazide diuretics
- Hypopituitarism (ateliotic dwarfism)
- Hypothyroidism[10]
- Lipodystrophy (congenital or acquired)
- Nephrotic syndrome
- Obesity[11]
- Pancreatitis
- Pregnancy
- Sepsis
- Smoking[12]
- Stress
References
- ↑ 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.
- ↑ 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.
- ↑ 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.