Lipoprotein disorders causes

Lipoprotein Disorders Microchapters
Patient Information
Overview
Causes
Classification Hyperlipoproteinemia Hypolipoproteinemia
Treatment

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]; Associate Editor(s)-in-Chief: Hardik Patel, M.D.

Synonyms and keywords: Hyperlipidaemia; hyperlipoproteinemia.

Overview

Hyperlipidemia involves abnormally elevated levels of any or all lipids and/or lipoproteins in the blood. It is the most common form of dyslipidemia (which also includes any decreased lipid levels).

Lipids (fat-soluble molecules) are transported in a protein capsule. The size of that capsule, or lipoprotein, determines its density. The lipoprotein density and type of apolipoproteins it contains determines the fate of the particle and its influence on metabolism.

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. 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

Hyperlipidemias may basically be classified as either familial (also called primary) caused by specific genetic abnormalities, or acquired (also called secondary) when resulting from another underlying disorder that leads to alterations in plasma lipid and lipoprotein metabolism. 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. 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.

Fredrickson classification of Hyperlipidemias

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
	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
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
Type V		144650		Increased VLDL production and Decreased LPL	VLDL and Chylomicrons		Niacin, fibrate	Creamy top layer & turbid bottom

File:Relative prevalence of familial hyperlipoproteinemias.png

Relative prevalence of familial forms of hyperlipoproteinemia

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), a condition caused by a lack of lipoprotein lipase activator.
• Chylomicronemia due to circulating inhibitor of lipoprotein lipase (Type Ic)

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

Main article: 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 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.

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

• 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
• Cushing's syndrome
• Connective tissue disorders
  • Dysglobulinemias (lupus, lymphoma, myeloma, Waldenström's macroglobulinemia)
  • Glycogen storage disease, type I
• Diabetes mellitus, type 2
• Hypothyroidism
• Hypopituitarism (ateliotic dwarfism)
• Lipodystrophy (congenital or acquired)
• Nephrotic syndrome
• Obesity
• Pancreatitis
• Pregnancy
• Sepsis
• Stress
• Smoking
• Drugs
  • Oral estrogens
  • Thiazide diuretics
  • Beta blockers
  • Atypical antipsychotic agents, such as clozapine and olanzapine
  • Antiretroviral drugs used for HIV infection, in particular the protease inhibitors
  • Bile acid binding resins
  • Cimetidine
  • Glucocorticoids
  • Isotretinoin

Causes by Organ System

Cardiovascular	Alagille syndrome
Chemical / poisoning	No underlying causes
Dermatologic	No underlying causes
Drug Side Effect	Amprenavir, Atazanavir sulfate, Atypical antipsychotics, Bendrofluazide, Beta blockers, Bexarotene, Chenodeoxycholic acid, Chlorthalidone, Clofibrate, Colesevelam hydrochloride, Colestyramine, Combined oral contraceptive pill, Cyclopenthiazide, Danazol, Desvenlafaxine, Doxazosin, Ethanol, Etretinate, Fosamprenavir, Gestrinone, Hydrochlorothiazide, Interferon alpha, Isotretinoin, Linagliptin, Lopinavir, Mitotane, Nelfinavir, Prazosin, Progestagens, Propofol, Protease inhibitors, Ritonavir, Rosiglitazone, Saquinavir, Sirolimus, Temsirolimus, Testosterone, Thiazide diuretics, Tipranavir, Tocilizumab, Tofacitinib, Torcetrapib
Ear Nose Throat	No underlying causes
Endocrine	Cushing syndrome, Diabetes mellitus type 2, Hypothyroidism, Metabolic syndrome, Hypopituitarism
Environmental	No underlying causes
Gastroenterologic	Cholestatic jaundice, Intrahepatic cholestasis, Malignant hepatopathy, Pancreatitis, Alagille syndrome
Genetic	Alagille syndrome, Alstrom syndrome, Analbuminaemia, Apolipoprotein C-II deficiency, Apoprotein E deficiency, Berardinelli-Seip congenital lipodystrophy, Carnitine palmitoyltransferase 1 deficiency, Chromosome 15q deletion, Familial alphalipoprotein deficiency, Familial defective apolipoprotein B-100, Familial hypertriglyceridaemia, Familial isolated vitamin E deficiency, Familial mixed hyperlipidemia, Fructose-1, 6-diphosphatase deficiency, Glycogen storage diseases, Lecithin cholesterol acyltransferase deficiency, Lipoprotein lipase deficiency, Niemann-Pick disease , Primary hyperlipoproteinemia , Primary hypolipoproteinemia, Smith-Lemli-Opitz syndrome, Werner syndrome
Hematologic	No underlying causes
Iatrogenic	Parenteral nutrition
Infectious Disease	Sepsis
Musculoskeletal / Ortho	Smith-Lemli-Opitz syndrome
Neurologic	Growth hormone secreting pituitary adenoma
Nutritional / Metabolic	Dysglobulinemia, LDL receptor deficiency, Omega-3 polyunsaturated fatty acids, Selenium deficiency, Vitamin E deficiency, Smith-Lemli-Opitz syndrome, Apolipoprotein C-II deficiency, Apoprotein E deficiency, Carnitine palmitoyltransferase 1 deficiency, Familial isolated vitamin E deficiency, Fructose-1, 6-diphosphatase deficiency, Glycogen storage diseases, Lecithin cholesterol acyltransferase deficiency, Lipoprotein lipase deficiency, Niemann-Pick disease , Primary hypolipoproteinemia
Obstetric/Gynecologic	Pregnancy
Oncologic	Growth hormone secreting pituitary adenoma
Opthalmologic	No underlying causes
Overdose / Toxicity	Amprenavir, Atazanavir sulfate, Atypical antipsychotics, Bendrofluazide, Beta blockers, Bexarotene, Chenodeoxycholic acid, Chlorthalidone, Clofibrate, Colesevelam hydrochloride, Colestyramine, Combined oral contraceptive pill, Cyclopenthiazide, Danazol, Desvenlafaxine, Doxazosin, Ethanol, Etretinate, Fosamprenavir, Gestrinone, Hydrochlorothiazide, Interferon alpha, Isotretinoin, Linagliptin, Lopinavir, Mitotane, Nelfinavir, Prazosin, Progestagens, Propofol, Protease inhibitors, Ritonavir, Rosiglitazone, Saquinavir, Sirolimus, Temsirolimus, Testosterone, Thiazide diuretics, Tipranavir, Tocilizumab, Tofacitinib, Torcetrapib
Psychiatric	Anorexia nervosa
Pulmonary	No underlying causes
Renal / Electrolyte	Chronic renal failure, Nephrotic syndrome, Alagille syndrome
Rheum / Immune / Allergy	Macrophage activation syndrome
Sexual	No underlying causes
Trauma	No underlying causes
Urologic	No underlying causes
Dental	No underlying causes
Miscellaneous	Alcohol abuse, Benign symmetrical lipomatosis, Exercise, Hight fat diet, Obesity, Positive family history, Sedentary lifestyle , Stress, Tobacco smoking

Causes in Alphabetical Order

Alagille syndrome Alcohol abuse Alstrom syndrome Amprenavir Analbuminaemia Anorexia nervosa Apolipoprotein C-II deficiency Apoprotein E deficiency Atazanavir sulfate Atypical antipsychotics Bendrofluazide Benign symmetrical lipomatosis Berardinelli-Seip congenital lipodystrophy Beta blockers Bexarotene Carnitine palmitoyltransferase 1 deficiency Chenodeoxycholic acid Chlorthalidone Cholestatic jaundice Chromosome 15q deletion Chronic renal failure Clofibrate Colesevelam hydrochloride Colestyramine Combined oral contraceptive pill Cushing syndrome Cyclopenthiazide Danazol Desvenlafaxine Diabetes mellitus type 2 Doxazosin Dysglobulinemia Ethanol Etretinate Exercise Familial alphalipoprotein deficiency Familial defective apolipoprotein B-100 Familial hypertriglyceridaemia Familial isolated vitamin E deficiency Familial mixed hyperlipidemia Fosamprenavir Fructose-1, 6-diphosphatase deficiency Gestrinone Glycogen storage diseases Growth hormone secreting pituitary adenoma Hight fat diet Hydrochlorothiazide

Hypopituitarism Hypothyroidism Interferon alpha Intrahepatic cholestasis Isotretinoin LDL receptor deficiency Lecithin cholesterol acyltransferase deficiency Linagliptin Lipoprotein lipase deficiency Lopinavir Macrophage activation syndrome Malignant hepatopathy Metabolic syndrome Mitotane Nelfinavir Nephrotic syndrome Niemann-Pick disease Obesity Omega-3 polyunsaturated fatty acids Pancreatitis Parenteral nutrition Positive family history Prazosin Pregnancy Primary hyperlipoproteinemia Primary hypolipoproteinemia Progestagens Propofol Protease inhibitors Ritonavir Rosiglitazone Saquinavir Sedentary lifestyle Selenium deficiency Sepsis Sirolimus Smith-Lemli-Opitz syndrome Stress Temsirolimus Testosterone Thiazide diuretics Tipranavir Tobacco smoking Tocilizumab Tofacitinib Torcetrapib Vitamin E deficiency Werner syndrome

References

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