Dysbetalipoproteinemia
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Lipoprotein Disorders Microchapters |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: Broad beta disease; broad beta hyperlipoproteinemia; broad-beta hyperlipoproteinemia; dysbetalipoproteinemia; familial dysbetalipoproteinemia; familial hypercholesterolemia with hyperlipemia; type III hyperlipoproteinemia
Overview
Familial dysbetalipoproteinemia is a disorder passed down through families in which there are high amounts of cholesterol and triglycerides in the blood. 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). Prevalence is 0.02% of the population.
Hyperlipoproteinemia type III, also known as dysbetalipoproteinemia or broad beta disease, is a rare genetic disorder characterized by improper breakdown (metabolism) of certain fatty materials known as lipids, specifically cholesterol and triglycerides. This results in the abnormal accumulation of lipids in the body (hyperlipidemia). Affected individuals may develop multiple yellowish, lipid-filled bumps (papules) or plaques on the skin (xanthomas). Affected individuals may also develop the buildup of fatty materials in the blood vessels (artherosclerosis) potentially obstructing blood flow and resulting in coronary heart disease or peripheral vascular disease. Most cases of hyperlipoproteinemia type III are inherited as an autosomal recessive trait.
Causes
A genetic defect causes this condition. The defect results in the build up of large lipoprotein particles that contain both cholesterol and triglycerides, a type of fat. The disease is linked to defects in the gene for apolipoprotein E in many cases.
Hypothyroidism, obesity, or diabetes can make the condition worse. Risk factors for familial dysbetalipoproteinemia include a family history of the disorder or coronary artery disease.
Differential Diagnosis
Symptoms of the following disorders can be similar to those of hyperlipoproteinemia type III. Comparisons may be useful for a differential diagnosis:
Hyperlipoproteinemias are a group of inherited lipid storage and transport diseases that are characterized by excessive levels of certain fats (lipoproteins) in the blood. In addition to hyperlipoproteinemia type III, this group of disorders includes hyperlipoproteinemia type I (familial hyperchylomicronemia); hyperlipoproteinemia type II (familial hyperbetalipoproteinemia); familial hyperlipoproteinemia type IV (carbohydrate induced hyperlipemia); and hyperlipoproteinemia type V (fat and carbohydrate hyperlipemia). Symptoms of all of these forms of hyperlipoproteinemia include the abnormal accumulation of fatty material in the walls that line medium and large arteries and the presence of multiple yellow fatty deposits (xanthomas) on certain areas of the skin. (For more information on these disorders, choose “Hyperlipoproteinemia” as your search term in the Rare Disease Database.)
Hyperlipoproteinemia type IV is an inborn error of metabolism characterized by an abnormal increase in the blood level of certain fats called triglycerides. The body’s ability to use sugar (glucose tolerance) may also be impaired. Symptoms include fatty nodules or plaques (xanthomas) on the arms, legs, and/or buttocks. Hyperlipoproteinemia type IV usually leads to the degeneration of blood vessels and heart disease. The liver and spleen may also be enlarged (hepatosplenomegaly). Hyperlipoproteinemia type IV is inherited as an autosomal dominant trait. (For more information on this disorder, choose “Hyperlipoproteinemia Type IV” as your search term in the Rare Disease Database.)
Hyperlipoproteinemia type I (familial hyperchylomicronemia) is a rare inherited disorder that prevents children born with it from transporting dietary cholesterol and/or triglycerides properly. (Chylomicrons are another lipoprotein-complex essential to the transport of fat from the stomach to various organs of the body.) In this case, the presence of extremely high levels of triglycerides does not commonly lead to hardening of the arteries (atherosclerosis) but potentially serious inflammation of the pancreas (pancreatitis) may accompany the symptoms of this disorder. Severe abdominal pain is experienced after eating fatty foods. Fatty growths on the skin (eruptive xanthomas) are not uncommon. People with this form must minimize the eating of dietary fats of any kind.
Symptoms
Symptoms may not be seen until age 20 or older.
Yellow deposits of fatty material in the skin called xanthomas may appear on the eyelids, palms of the hands, soles of the feet, or on the tendons of the knees and elbows.
Atherosclerosis develops. There may be early chest pain (angina) or decreased blood flow to specific parts of the body, causing transient ischemic attacks of the brain or peripheral artery disease.
Exams and Tests
Tests that may be done to diagnose this condition include:
- Angiogram
- Genetic testing for apolipoprotein E (apoE)
- Heart stress test
- Total cholesterol
- Triglyceride level
- Very low density lipoprotein (VLDL) test
Treatment
The goal of treatment is to control underlying conditions such as obesity, hypothyroidism, and diabetes.
Reducing calories, saturated fats, and cholesterol may significantly reduce cholesterol levels.
If high cholesterol and triglyceride levels continue despite diet changes, your doctor may recommend medicine to lower your cholesterol. Medicine to lower cholesterol levels include:
- Bile acid-sequestering resins
- Fibrates
- Nicotinic acid
- Statins
Prognosis
Persons with this condition have an increased risk for coronary artery disease and peripheral vascular disease.
With treatment, most people show a significant reduction in lipid levels.
Possible Complications
- Heart attack
- Stroke
- Peripheral vascular disease
- Intermittent claudication
- Gangrene of the lower extremities
Prevention
Screening the family members of those with familial dysbetalipoproteinemia may lead to early detection and treatment.
Early treatment and avoiding other risk factors for vascular disease (such as smoking) are crucial to preventing early heart attacks, strokes, and blocked blood vessels.