Hyperlipoproteinemia refers to a group of acquired and inherited disorders whose common denominator is excessive levels of lipids (fats) in the blood, caused by a metabolic disorder. It is also referred to as hyperlipidemia. The condition is a major cause of coronary heart disease (CHD).
Description
The acquired form of hyperlipoproteinemia occurs as a condition secondary to another disease, such as diabetes mellitus, hypothyroidism, or nephrosis. The hereditary, or inherited, form of hyperlipoproteinemia is classified into five major types.
Lipids are an essential part of human metabolism and are a primary source of energy for the body. Lipids are produced by cells in the body and along with carbohydrates and proteins, are components of all life. But lipids are essentially oil-based and as such do not mix with a water-based liquid such as blood. Yet both must be carried through the body's circulatory system. So to get around this obstacle, lipids attach themselves to proteins. This combination of lipids and proteins is called lipoproteins, which are water-soluble particles that can be carried through the blood stream.
Some of the chemicals in the lipoproteins are fatty nutrients that are absorbed by the intestines for use in other parts of the body. Cholesterol is carried by lipoproteins through the blood stream to the liver and ultimately to the bowel for excretion. If the substances in the lipoproteins are not properly balanced, cholesterol will stay in the tissues instead of being excreted. It can also build up in blood vessels, eventually restricting and even blocking blood flow.
There are five different densities of lipoproteins, each containing triglycerides, cholesterol, phospholipids (lipids with phosphorus attached), and special proteins. The lipoproteins are high-density lipoproteins (HDL), low-density lipoproteins (LDL), intermediate-density lipoproteins, very low-density lipoproteins (VLDL), and chylomicrons. HDL is commonly called "good" cholesterol and LDL "bad" cholesterol. The two major lipoprotein groups are HDL and LDL.
HDL helps prevent fat buildup throughout the body by carrying cholesterol from the arteries to the liver, where it is disposed of. Abnormally low levels of HDL, fewer than 30 milligrams per deciliter (mg/dL) of blood, are associated with a greater risk for coronary heart disease and stroke. LDL carries most of the cholesterol in the body, so an excess of LDL, usually 160 mg/dL of blood, can clog the arteries with cholesterol buildup. This can lead to atherosclerosis, commonly referred to as hardening of the arteries, or acute myocardial infarction (heart attack).
The five types of inherited hyperlipoproteinemia are:
Type I, characterized by high levels of chylomicrons and triglycerides and a deficiency of lipoprotein lipase, an enzyme that accelerates the breakdown of lipoproteins. Disease onset is usually in infancy.
Type II, broken into two subtypes, type II-a and type II-b. Both subtypes display high levels of blood cholesterol. People with type II-b also have high levels of triglycerides in their blood. Disease onset is usually after age 20.
Type III, also called broad beta disease, is characterized by high blood levels of cholesterol and triglycerides, and the presence of a lipoprotein called apolipoprotein E (apo E) genotype E2/E2. Disease onset is usually in adults.
Type IV, characterized only by high triglyceride levels in the blood. Disease onset is usually during puberty or early adulthood.
Type V, characterized by increased blood levels of chylomicrons and triglycerides and low levels of LDL and HDL. Disease onset is usually in children or adults.
Genetic profile
Type III hyperlipoproteinemia is an autosomal recessive disorder that affects males and females. Autosomal means that the gene does not reside on the sex chromosome. People with only one abnormal gene are carriers but since the gene is recessive, they do not have the disorder. Their children could be carriers of the disorder but not show symptoms of the disease. Both parents must have one of the abnormal genes for a child to have symptoms of type III hyperlipoproteinemia. When both parents have the abnormal gene, there is a 25% chance each child will inherit both abnormal genes and have the disease. There is a 50% chance each child will inherit one abnormal gene and become a carrier of the disorder but not have the disease itself. There is a 25% chance each child will inherit neither abnormal gene and not have the disease nor be a carrier.
The other types of hyperlipoproteinemia are autosomal dominant. This means they occur when an abnormal gene from one parent is capable of causing the disease even though the matching gene from the other parent is normal. The abnormal gene dominates the outcome of the gene pair. This means that there is a 50% chance that each child of the couple will have the disease. Consequently, there is a 50% chance each child will not inherit the defective gene and will not have the disease.
Demographics
Hyperlipoproteinemia can affect people regardless of age, gender, race, or ethnicity. All adults, starting at age 20, should be tested for hyperlipoproteinemia at least once every five years, recommends the National Cholesterol Education Program (NCEP) of the National Institutes of Health (NIH). People considered at high risk for hyperlipoproteinemia should be tested more often and include those with a diet high in fat and cholesterol, have a family history of the disorder, use oral contraceptive or take estrogen, or who have diabetes mellitus, hypothyroidism, nephrosis, or alcoholism. Ethnic groups that have a higher risk of developing hyperlipoproteinemia include Latinos, Native Americans, African-Americans, and Pacific Islanders.
Signs and symptoms
It is very common for people with hyperlipoproteinemia to show no outward signs of the disorder. But there are several general signs that may indicate a person has the disorder, including obesity, yellowish skin, fatty yellow patches or nodules on the skin, especially the eyelids, neck, and back, inflamed tendons, an enlarged spleen, inflamed pancreas, nausea and vomiting, or abdominal pain. However, these are also symptoms of a variety of other conditions so for hyperlipoproteinemia to be diagnosed, blood tests are needed.
Diagnosis
Diagnosis involves a series of blood tests to measure lipid levels and determine the type of hyperlipoproteinemia. Blood tests, usually taken after a 12-hour fast, include measurement of total serum cholesterol, HDL, LDL, VLDL, triglycerides, and for the presence of apolipoprotein E. When hyperlipoproteinemia secondary to another disorder has been excluded and inherited hyperlipoproteinemia seems likely, first-degree relatives should be tested. These include parents, children, and siblings.
Treatment and management
Hyperlipoproteinemia treatment is usually based on a three-fold attack: diet, exercise, and lipid-lowering medications. People who are overweight should begin a program to slowly but consistently lose weight until they are at or near the recommended weight for their height and body frame. It is essential to eat a diet low in fat. Exercise also plays a vital role. A minimum of 20 minutes of aerobic exercise three times a week is beneficial and 30 minutes or more daily is ideal. The exercise can take the form of running, jogging, cycling, swimming, cardiovascular machines, or even walking briskly.
Eating healthy and exercising regularly, while extremely beneficial, are not always enough to bring lipid levels to the desired range. Prescription medications are often required. There is a wide range of medications available to manage lipid levels. The most prescribed are HMG-CoA-reductase inhibitors, commonly called "statins," which hinder the body's production of cholesterol. Statins include cerivstatin (Baycol), fluvastatin (Lescol), lovastatin (Mevacor), pravastatin (Pravacol), atorvastatin (Lipitor), and simvastatin (Zocor). Other first-line medications include bile acid sequestrants, cholestyramine (Questran), colesevelan (Welchol), and colestipol (Colestid). Also, probucol (Lorelco) is sometimes used.
The type of drug prescribed may vary, depending on the lipid test results and the type of hyperlipoproteinemia that is diagnosed. For example, people with type III of the disorder respond better when prescribed fibric acid derivatives such as gemfibrozil (Lopid), clofibrate (Atromid-S), and fenofibrate (Tricor) or nicotinic acid (niacin).
Other factors which have a negative effect on hyperlipoproteinemia include smoking, excessive alcohol consumption, and stress. It is also important to treat underlying conditions, such as diabetes, heart disease, pancreatitis (inflamed pancreas), and thyroid problems.
Prognosis
The prognosis is good for type I hyperlipoproteinemia with treatment. For type II, the prognosis is good for II-b and fair for II-a with early diagnosis and treatment. The prognosis for type III is good when the prescribed diet is strictly followed. The prognosis is uncertain for types IV and V, due to the risk of developing premature coronary artery disease in type IV and pancreatitis in type V.
BOOKS
Carlson, Lars., et al. Treatment of Hyperlipoproteinemia. New York: Lippincott-Raven Publishers, 1984.
Rifkind, Basil M., ed. Drug Treatment of Hyperlipidemia. New York: Marcel Dekker, 1991.
PERIODICALS
Abel, Allen. "The Tumblebrutus Solution." Saturday Night (February 1997): 26-29.
Baer, Daniel. "Lipid Tests." Medical Laboratory Observer (May 1992): 11-14.
Gotto, Antonio M. Jr., et al. "Hyperlipidemia: A Complete Approach." Patient Care (February 15, 1989): 34-48.
ORGANIZATIONS
Inherited High Cholesterol Foundation. University of Utah School of Medicine, 410 Chipeta Way, Room 167, Salt Lake City, UT 84104. (888) 244-2465.
National Cholesterol Education Program. National Heart, Lung and Blood Institute. PO Box 30105, Bethesda, MD 20824. (301) 592-8573. <http://www.nhlbi.nih.gov>.
National Organization for Rare Disorders (NORD). PO Box 8923, New Fairfield, CT 06812-8923. (203) 746-6518 or (800) 999-6673. Fax: (203) 746-6481. <http://www.rarediseases.org>.
WEBSITES
"Hyperlipidemia Types I, II, III, IV, V (Hyperlipoproteinemia)." HealthGate. <http://www.healthgate.com/ped/sym204.html>.
