Gale Encyclopedia of Genetic Disorder / Gale Encyclopedia of Genetic Disorders, Two Volume Set - Volume 2 - M-Z - I

diminished appetitie, and fatigue may occur prior to the onset of the more serious symptoms. The exact combination and severity of these symptoms varies widely between cases and types of prion disease.

CJD, the most common of the human prion diseases, is characterized by a rapid deterioration in mental function from confusion and memory loss into severe dementia, accompanied by loss of muscular control (ataxia) and twitching or spasmodic motion (myoclonus). Other symptoms include vision and speech impairment. A scan of electrical activity in the brain, called an electroencephalogram (EEG), will often show an abnormal periodic spike pattern. The onset of symptoms usually occurs when the patient is over age 50 and death follows within one to five years. Microsopic holes, or vacuoles, in the brain tissue, which give it a “spongiform” appearance, are characteristic of CJD.

Gertsmann-Straussler-Scheinker syndrome (GSS) encompasses a variety of disorders. One form of the disease (the ataxic form) is first characterized by an unsteady walk sometimes accompanied by leg pains. These motor problems get worse over several years and are finally accompanied by mental and behavioral breakdown. By contrast, dementia is the main characteristic of the telencephalic form of GSS, accompanied by rigidity, the inability to make facial expressions, tremors, and stuttering or stammering. In another form of the disease, GSS with neurofibrillary tangles, the main features are loss of muscle coordination (ataxia), tremors, and progressive insanity. As in CJD, the affected individuals are usually in their fifties or older, and the progression of the disease may take from two to six years.

The most noticeable sign of fatal familial insomnia (FFI) is the untreatable and progressively worse difficulty in sleeping. The affected individual then begins to experience complex hallucinations which are often enacted dreams. Excessive sweating, irregular heartbeat, high blood pressure, and hyperventilation are other symptoms. Motor impairment may be present. Shortened attention span and memory loss has been observed. In the terminal stages, stupor and coma precede death. The average age at onset of symptoms is the mid-forties, and the disease progresses rapidly with death resulting after about one year. Autopsy reveals the formation of dense tangles of neural fibers and astrocytes in the thalamus region of the brain.

Kuru was called the “shivering” disease by the Fore tribe members because its primary symptom was twitching and shaking of the body. This twitching began slowly and was not present when the person was completely still, but then progressively worsened until any attempt at motion led to drastic and uncontrollable body movements, and the individual could no longer stand or walk. Mental insanity usually did not appear until the terminal

K E Y T E R M S

Ataxia—A deficiency of muscular coordination, especially when voluntary movements are attempted, such as grasping or walking.

Iatrogenic—Caused by (-genic) doctor (iatro-). An iatrogenic condition is a condition that is caused by the diagnosis or treatment administered by medical professionals. Iatrogenic conditions may be caused by any number of things, including: unsterile medical instruments or devices, contaminated blood or implantations, or contaminated air within the medical facility.

Isomers—Two chemicals identical in chemical composition (contain the same atoms in the same amounts) that have differing structures. The normal prion protein and the infectious prion protein are conformational isomers of one another. They have the same chemical structures, but for some reason, assume different shapes.

Myoclonus—Twitching or spasms of a muscle or an interrelated group of muscles.

Prion—A term coined to mean “proteinaceous infectious particle.” Prior to the 1982 discovery of prions, it was not believed that proteins could serve as infectious agents.

Protease—An enzyme that acts as a catalyst in the breakdown of peptide bonds.

Spongiform encephalopathy—A form of brain disease characterized by a “spongelike” appearance of the brain either on autopsy or via magnetic resonance imaging (MRI).

stages of the disease. The onset of symptoms usually occurred in middle-aged individuals and the course of the disease was short: three to 12 months.

The early signs of new variant CJD are most often psychiatric disturbances. Abnormal sensations of prickling or itching (paresthesia) or pain even from light touches (dysesthesia) are often present. So far, individuals affected with new variant CJD are much younger in age, typically teenagers and young adults. The duration of the disease is one to two years. As in CJD, vacuoles are present in the brain, but they are associated with dense deposits, or plaques, of the abnormal PrP isomer.

Diagnosis

Because of the many different forms of the disease and the overlap in symptoms with other common syn-

diseases Prion

Progeria syndrome

dromes such as Alzheimer disease, prion diseases are often difficult to diagnosis. A diagnosis of prion disease should be considered in any adult patient with signs of neurological impairment such as uncontrollable body movements, confusion, loss of memory, and cognitive degeneration, or psychiatric abnormality. Periodic discharges of brain waves, as observed on an electroencephalogram (EEG), are present in many, but not all, cases of prion disease. A magnetic resonance imaging (MRI) scan of the brain can rule out other causes of brain disease and potentially identify some abnormalities associated with prion disease. A biopsy, or sampling, of brain tissue can reveal the presence of abnormal PrP, although this procedure is generally not used in elderly patients. Genetic testing can reveal those cases of prion disease that are caused by mutations. Bismuth, mercury, or lithium poisoning result in symptoms that are quite similar to prion disease. These poisonings can be differentially diagnosed by blood tests.

The diagnosis of prion disease can be definitively confirmed by the transmission of the disease to an animal host such as a genetically engineered mouse. However, the transmission period may be quite long, as much as six to seven months. After death, prion disease can also be validated by autopsy of the brain tissue.

Patients eventually identified with prion disease have been initially diagnosed with many other diseases including Alzheimer disease, Huntington disease, Parkinson disease, schizophrenia, multiple sclerosis, and myoclonic epilepsy. This illustrates the difficulty in identifying the disease and the importance of careful diagnosis to avoid unnecessary treatments.

Treatment and management

At present, there is no known treatment that can prevent or reverse the transformation of the prion protein into its aberrant form. All treatments for prion disease are directed towards management of the symptoms. These treatments may include psychoactive drugs, electroconvulsive therapy (ECT), and professional care to ensure that the loss of physical and mental functions do not lead to accidental injury or death. Research into more advanced treatments is focusing on the application of gene therapies to block the formation of infectious PrP and drugs, which could act to stabilize the normal PrP structure. As with any inherited disease, genetic counseling is important in the management of the familial forms of prion disease.

Prognosis

Since the forms of prion diseases vary widely, the age at onset and rate of worsening of symptoms are also

quite variable, but all prion diseases are incurable and fatal with a duration anywhere from a few months to several years after onset.

Resources

PERIODICALS

Mastrianni, J., R. Roos “The prion diseases.” Seminars in Neurology (October 2000): 337-352.

Prusiner, Stanley. “The prion diseases.” Scientific American (January 1995): 48-57.

ORGANIZATIONS

Creutzfeldt-Jakob Disease Foundation, Inc. PO Box 611625, Miami, FL 33261-1625. Fax: (954) 436-7591.http://www.cjdfoundation.org .

Human BSE Foundation (United Kingdom). 0191 389 4157.http://humanbse.foundation@virgin.net .

WEBSITES

CJD Voice. http://members.aol.com/larmstr853/cjdvoice/ cjdvoice.htm (February 23 2001).

Johns Hopkins Department of Neurology Resource on Prion

Disease. http://www.jhu-prion.org (February 23, 2001).

The Official Mad Cow Disease Home Page.

http://www.mad-cow.org (February 23, 2001).

Paul A. Johnson

I Progeria syndrome

Definition

Progeria syndrome is an extremely rare genetic disorder of unknown origin that manifests as premature aging in children. Progeria affects many parts of the body including the skin, bones, and arteries.

Description

Dr. Jonathan Hutchinson in 1886 and Dr. Hastings Gilford in 1904 first described this syndrome. The word progeria is coined from the Greek word geras, which means old age. Progeria syndrome is also known as Hutchinson-Gilford progeria syndrome, HGPS or Gilford syndrome.

Most patients appear normal at birth. Signs and symptoms usually begin to develop within the first one to two years of life. Changes in skin and failure to thrive (failure to gain weight) are usually evident first, the exception being four reported cases of possible neonatal progeria. All four infants died before twenty months of

age. Death in these cases appears to be related to intrauterine growth retardation and presentation of progeria signs and symptoms at birth. The neonatal cases did not exhibit the development of arteriosclerosis (hardening of the arteries). Arteriosclerosis is the most serious complication of progeria. Complications secondary to arteriosclerosis in childhood, adolescence, or adulthood are the leading cause of death.

Patients with progeria syndrome develop many other signs and symptoms which present a classical appearance. The majority of patients with progeria resemble each other. Common external findings include aging at an accelerated rate, alopecia (hair loss), prominent scalp veins, absence of fat under the skin (subcutaneous fat), scleroderma (thickening of the skin), a pinched nose, small face and jaw (micrognathia) relative to head size (bird face), delayed tooth formation, high pitched voice, and impaired or absence of sexual development. Patients are also known to experience stiffening of various joints, bone structure abnormalities, and the development of arteriosclerosis. Patients with progeria syndrome experience average intelligence and their cognitive abilities are usually not affected.

Genetic profile

Evidence suggests that the gene for progeria may be located on chromosome 1. Progeria is believed to be passed on in an autosomal dominant new mutation fashion. The disorder is transmitted to children by autosomal dominant inheritance. This means that either affected parent (father or mother) has a 50% chance of having a child (regardless of gender) with the disorder. New mutation refers to the chance change in the structure of a gene resulting in alterations in its function. This new mutation is believed to happen at conception sporadically and permanently (since neither parent is affected). New mutations occur as a result of both genetic and environmental factors. New mutations can be either chromosomal abnormalities or point mutations (specific alterations in the building blocks of genes called nucleotides). Research is ongoing to identify a more specific genetic mutation that causes progeria syndrome.

Demographics

Occurrence of progeria is sporadic and rare, though studies suggest frequency may be related to increased parental age and increased average difference in age of parents. Approximately 100 cases have been reported to date in the world with the reported incidence (number of absolute occurrence) being one in eight million.

K E Y T E R M S

Arteriosclerosis—Hardening of the arteries that often results in decreased ability of blood to flow smoothly.

Failure to thrive—Significantly reduced or delayed physical growth.

Progeria—Genetic abnormality that presents initially as premature aging and failure to thrive in children.

Scleroderma—A relatively rare autoimmune disease affecting blood vessels and connective tissue that makes skin appear thickened.

Signs and symptoms

Progeria syndrome is progressive. Signs develop over time.

•General—Patients are short and weigh less than is appropriate for height. Patients usually do not grow taller than 3.7 ft (1.15 m) or weigh over 40 lb (15 kg). Patients with progeria do not usually exhibit mental impairment.

•Skin—Skin is usually thin, dry, and wrinkled. The skin in the hands and feet is pushed inwards. The skin also exhibits color (pigmentation) changes, which presents clinically as yellow-brownish spots. Patients also have a decrease in fat below the skin (subcutaneous) except in the area below the navel. The nails of patients with progeria are small, thin, and poorly developed. Patients experience alopecia (hair loss) of the scalp, eyelashes, and eyebrows. Scalp veins become visible and prominent as hair loss progresses.

•Bones—There are several abnormalities in the skeletal structure. Refer to complete description under diagnosis heading.

•Eyes—Patients often appear to have prominent eyes. This is in part secondary to the alterations in bone structure of the face. Patients also may experience farsightedness (hyperopia) and astigmatism. Astigmatism refers to changes in the structure of the lens and cornea (parts of the internal structure of the eyes), which alter the eyes’ ability to focus incoming visual images.

Diagnosis

Diagnosis is based upon physical appearance. Diagnosis is usually made within the first two years of life when patients develop skin changes and fail to grow.

syndrome Progeria

Progeria syndrome

Signs of premature aging in the hands of a patient diagnosed with progeria. (Custom Medical Stock Photo, Inc.)

Patients with progeria eventually develop skeletal system (bone and joint) changes. Patients show characteristic radiographic (x ray) findings. In general the skeleton is hypoplastic (underdeveloped). Patients have persistent anterior fontanelles (soft spots of skull in newborn children). Patients with progeria may also develop deterioration of the collarbone and end of the fingers. Hip joints are affected because of alteration in the bone structure of the femur (the bone which extends from the knee upwards to the pelvis). This causes the femur to sit in more of a straight-line relationship to the hip joint. This is abnormal and causes a wide-based gait (walking) and the appearance of a horse-riding stance. It is described as coxa valga. Some patients also show an increase in the amount of hyaluronic acid secreted in the urine. Hyaluronic acid is a substance in the body that is found in tissues such as cartilage. Cartilage is a flexible connective tissue that works as a joint stabilizer.

Treatment and management

There is no cure for progeria. Treatment is symptomatic and aimed at providing psychological support. Palliative measures such as wearing a wig may be beneficial. Relief from chest pain due to changes in arteries can be accomplished by nitroglycerin. Nitroglycerin is a medication that relaxes muscle fibers in blood vessels causing them to expand or dilate. This permits proper blood flow to affected areas, which enables cells and tissues to receive adequate amounts of the oxygen necessary for cell maintenance.

Experimental research management

Recent evidence suggested the benefit of giving nutritional therapy and growth hormone supplementation. The combination treatment of nutritional therapy and growth hormone supplementation demonstrated an increase in

growth of Progeria patients, an increase in growth factors (chemicals which promote formation) within the blood, and a decrease in the patient’s basal metabolic rate. Basal metabolic rate is the minimum amount of energy (calories) that an individual needs to ingest on a daily basis in order to execute normal activities and tasks.

Arteriosclerosis is most prominent in coronary (heart) arteries and the aorta (the largest artery in the body, which has many branches supplying oxygen filled blood to cells and tissues). Research indicates successful outcome from aggressive treatment of arteriosclerosis utilizing techniques such as coronary artery bypass (reconstruction of the heart arteries) or coronary artery balloon dilation (stretching the heart arteries in an attempt to allow increased blood flow).

Prognosis

Age of death ranges from seven to 27 years. One documented case reports an individual living to be 45 years of age. Death is usually secondary to arteriosclerosis complications such as heart failure, myocardial infarction (heart attack), or coronary thrombosis (when a clot from the heart moves to another location cutting the flow of blood to the new location).

Resources

BOOKS

Nora, J.J., and F.C. Fraser. Medical Genetics: Principles and

Practice. Philadelphia: Lea & Febiger, 1989. Wiedemann, H.R., J. Kunze, and F.R. Grosse. “Progeria.” In

Clinical Syndromes. 3rd ed. Edited by Gina Almond, 306–7. St. Louis: Mosby, Inc., 1997.

PERIODICALS

Sivaraman, D.M. Thappa., M. D’Souza, and C. Ratnakar. “Progeria (Hutchinson-Gilford): A Case Report.” Journal of Dermatology 26, no. 5 (May 1999): 324–28.

ORGANIZATIONS

Children Living with Inherited Metabolic Diseases. The Quadrangle, Crewe Hall, Weston Rd., Crewe, Cheshire, CW1-6UR. UK 127 025 0221. Fax: 0870-7700-327.http://www.climb.org.uk .

International Progeria Registry. IBR Dept. of Human Genetics, 1050 Forest Hill Rd., Staten Island, NY 10314. (718) 4945333. wtbibr@aol.com.

WEBSITES

The Council of Regional Networks for Genetic Services.http://www.cc.emory.edu/PEDIATRICS/corn/corn

.htm .

The National Society of Genetic Counselors.http://www.nsgc.org/Resource .

Laith Farid Gulli, MD

Nicole Mallory, MS

Progressive tapetochoroidal dystrophy see

Choroideremia

I Propionic acidemia

Definition

Propionic acidemia is an inborn error of metabolism: a rare inherited disorder in which the body is unable to break down and use certain proteins properly. As a result, massive amounts of organic compounds (such as propionic acid, ketones, and fatty acids) build up in the blood and urine, interfering with normal body functions and development.

Description

Propionic acidemia, first described in 1961, usually shows up in the first few weeks after birth and, if untreated, results in mental and physical impairment. The disorder can have a broad range of clinical outcomes, ranging from the severe form that is fatal to newborns to the mild, late-onset form associated with periodic attacks of ketoacidosis, when organic compounds build up in the blood and urine. Other names for the disorder include ketotic hyperglycinemia, hyperglycinemia with ketoacidosis and lactic acidosis (propionic type), and propionyl CoA carboxylase (PCC) deficiency, types I and II.

Propionic acidemia can occur in isolation, or it can be a feature of multiple carboxylase deficiency, a condition involving abnormal production of many enzymes— all of which need biotin (a form of vitamin B)—as the result of an abnormality in biotin metabolism. Propionic acidemia is characterized by deficiency of an enzyme, propionyl CoA carboxylase, which the body requires to break down the amino acids isoleucine, valine, threonine, and methionine (chemical building blocks of proteins). The deficiency can be caused by abnormal genes for making propionyl CoA carboxylase (isolated propionic acidemia) or by abnormal genes for metabolizing biotin (propionic acidemia resulting from multiple carboxylase deficiency).

Genetic profile

Propionic acidemia is an autosomal recessive disorder; that is, if a man and woman each carry one abnormal gene, then 25% of their children are expected to be born with the disorder. Two genes, PCCA and PCCB, code for the two parts (alpha and beta subunits) of the propionyl CoA carboxylase molecule.

The PCCA gene controls the production of alpha subunit and is on chromosome 13. Alterations in the PCCA gene result in Type I propionic acidemia.

Researchers have identified 19 disease-causing mutations in the PCCA gene. Eight of these mutations result in an incomplete alpha subunit. Six mutations prevent the alpha subunit from binding biotin, which is required for propionyl CoA carboxylase to work properly, and results in multiple carboxylase deficiency. People who inherit two abnormal PCCA genes (homozygotes) produce only 1–5% of the normal amount of propionyl CoA carboxylase. People who inherit one normal and one abnormal PCCA gene (heterozygotes) produce 50% of the normal amount of enzyme.

The PCCB gene, which controls the production of beta subunit, is on chromosome 3. Mutations in this gene are responsible for Type II propionic acidemia.

Twenty-eight disease-causing mutations have been found in the PCCB gene. In people of Caucasian, Spanish, and Latin American heritage, researchers have found the most frequent mutation in about 32% of those with propionic acidemia. In people of Japanese heritage, two other mutations are most prevalent, occurring in 25% and 31% of Japanese patients. Homozygotes for the PCCB gene produce propionyl CoA carboxylase in amounts similar to homozygotes for the PCCA gene, but heterozygotes for the PCCB gene produce nearly normal amounts of propionyl CoA carboxylase. This is probably because many more beta subunits (four to five times more) are produced than alpha subunits, so even with decreased PCCB gene activity, enough beta subunits are available to combine with alpha subunits to make a complete molecule of propionyl CoA carboxylase.

Demographics

The frequency with which propionic acidemia occurs throughout the world is unknown because it is a rare disorder. Its occurrence does not appear to be specific to any particular population group. Considered to be prevalent among Inuits in Greenland, propionic acidemia has also been identified in other populations, including Austrian, Spanish, Latin American, Saudi Arabian, Amish, and Japanese people. Males and females are equally likely to be affected.

Signs and symptoms

Newborns with propionic acidemia are typically small and pale with poorly developed muscles. Symptoms that usually appear in the first weeks of life include poor feeding, vomiting, listlessness (lethargy), and ketoacidosis. Less often, infants with the disorder

acidemia Propionic

Propionic acidemia

K E Y T E R M S

Amino acid—Organic compounds that form the building blocks of protein. There are 20 types of amino acids (eight are “essential amino acids” which the body cannot make and must therefore be obtained from food).

Biotin—A growth vitamin of the vitamin B complex found naturally in liver, egg yolks, and yeast.

Ketoacidosis—A condition that results when organic compounds (such as propionic acid, ketones, and fatty acids) build up in the blood and urine.

Multiple carboxylase deficiency—A type of propionic acidemia characterized by an inability to metabolize biotin.

Propionic acid—An organic compound that builds up in the body if the proper enzymes are not present.

Propionyl CoA carboxylase—An enzyme that breaks down the amino acids isoleucine, valine, threonine, and methionine.

experience loss of body fluids (dehydration), seizures, and enlarged livers.

In some patients, the disorder appears later in life. Signs include facial abnormalities, such as puffy cheeks and an exaggerated “Cupid’s bow” upper lip. Patients with late-onset propionic acidemia may have acute inflammation of the brain (encephalopathy) or be developmentally delayed. These patients may have periodic attacks of ketoacidosis, usually brought on by eating too much protein, becoming constipated, or having frequent infections.

Patients with propionic acidemia as the result of having multiple carboxylase deficiency often have ketoacidosis and their urine may have a distinct “tom cat’s urine” odor. These patients may also have skin rash and loss of hair (alopecia).

Diagnosis

Physicians have only a few tests available that allow them to differentiate propionic acidemia from other inborn errors of metabolism. Tests that are absolutely specific for the disorder involve the measurement of propionyl CoA carboxylase and chemicals related to the reactions it affects. These tests are fairly uncommon and do not have published normal values.

Prenatal diagnosis of propionic acidemia is possible using cells obtained by amniocentesis. The cells can be tested for decreased activity of propionyl CoA carboxylase, for their ability to bind propionic acid, or for their methylcitrate levels.

In a newborn child, propionyl CoA carboxylase activity can be measured in white blood cells (leukocytes) from cord blood (blood from the umbilical cord). The infant’s blood and urine can be tested for increased levels of propionic acid. These levels are tested as well in older children and adults who are suspected of having the disorder.

Physicians can use genetic tests to analyze DNA and identify the specific gene, PCCA or PCCB, that is abnormal.

Treatment and management

The accepted treatment for propionic acidosis is a low-protein diet. Daily protein intake must be limited to 0.5–1.5 g/kg. Patients should eat frequent meals and avoid fasting, because fasting increases the body’s need for propionyl CoA carboxylate.

A low-protein diet keeps the number of ketoacidosis attacks to a minimum; however, such a diet does not prevent attacks. Physicians treat attacks of ketoacidosis by removing all protein from the patient’s diet and giving the patient sodium bicarbonate and glucose. If the attack is severe, proteins may be removed from the patient’s stomach by peritoneal dialysis.

Some patients may respond to a single oral dose (100 mg/kg) of L-carnitine, an organic compound. Others may be helped by antibiotics, which reduce the number of bacteria that produce propionic acid in the stomach. These are experimental treatments and have not been tested for long-term effects.

Patients with multiple carboxylase deficiency may receive biotin supplements (10 mg daily), which provide immediate, long-lasting improvement. Biotin supplements are not effective, however, for patients with other types of propionic acidemia.

Prognosis

The future of patients with propionic acidemia depends on the severity of the disorder. Left untreated, propionic acidemia in infants results in coma and death. With early diagnosis and treatment, some children are intellectually normal, while others’ lives may be complicated by mental retardation and abnormal physical development. Some with popionic acidemia may be identified only during family studies. For patients with late-onset propionic acidemia, the disease can be controlled to some

extent by diet, but many of these patients will also be mentally and physically delayed.

Resources

BOOKS

Fenton, Wayne A., Roy A. Gravel, and David S. Rosenblatt. “Disorders of Propionate and Methylmalonate Metabolism.” In The Metabolic and Molecular Bases of Inherited Disease. 8th ed. Vol. 2. Ed. Charles R. Scriver, et al. New York: McGraw-Hill, 2001.

PERIODICALS

Campeau, Eric, et al. “Detection of a Normally Rare Transcript in Propionic Acidemia Patients with mRNA Destabilizing Mutations in the PCCA Gene.” Human Molecular Genetics 8, no. 1 (1999): 107–13.

Muro, Silvia, et al. “Identification of Novel Mutations in the PCCB Gene in European Propionic Acidemia Patients.”

Human Mutation: Mutation in Brief no. 253 (1999). Ravn, Kirstine, et al. “High Incidence of Propionic Acidemia in

Greenland is Due to a Prevalent Mutation, 1540insCCC, in the Gene for the Beta-Subunit of Propionyl CoA Carboxylase.” American Journal of Human Genetics 67 (2000): 203–6.

ORGANIZATIONS

Children Living with Inherited Metabolic Diseases. The Quadrangle, Crewe Hall, Weston Rd., Crewe, Cheshire, CW1-6UR. UK 127 025 0221. Fax: 0870-7700-327.http://www.climb.org.uk .

Organic Acidemia Association. 13210 35th Ave. North, Plymouth, MN 55441. (763) 559-1797. Fax: (863) 6940017. http://www.oaanews.org .

Organic Acidemias UK. 5 Saxon Rd., Ashford, Middlesex, TW15 1QL. UK (178)424-5989.

WEBSITES

Propionyl CoA Carboxylase Website. http://www.uchsc.edu/ sm/cbs/pcc/pccmain.htm .

Linnea E. Wahl, MS

Propionyl CoA carboxylase (PCC) deficiency see Propionic acidemia

I Prostate cancer

Definition

The prostate, a gland found only in men, is part of the reproductive system. Prostate cancer is a disease in which the cells of the prostate become abnormal and start to grow uncontrollably, forming tumors. Tumors that can spread to other parts of the body are called malignant

tumors or cancers. Tumors that are not capable of spreading are said to be benign.

Description

The prostate is a gland that produces the semen, the fluid that contains sperm. The prostate is about the size of a walnut and lies just beneath the urinary bladder. Usually prostate cancer is slow growing, but it can grow faster in some instances. As the prostate cancer grows, some of the cells break off and spread to other parts of the body through the lymphatic or the blood systems. This is known as metastasis. The most common sites of spreading are the lymph nodes and various bones in the spine and pelvic region.

The cause of prostate cancer is not clear; however, several risk factors are known. The average age at diagnosis of prostate cancer is around 72. In fact, 80% of prostate cancer cases occur in men over the age of 65. As men grow older, the likelihood of getting prostate cancer increases. Hence, age appears to be a risk factor for prostate cancer. Race may be another contributing factor. African-Americans have the highest rate of prostate cancer in the world, while the rate in Asians is one of the lowest. However, although the rate of prostate cancer in native Japanese is low, the rate in Japanese-Americans is closer to that of white American men. This suggests that environmental factors also play a role in prostate cancer.

There is some evidence to suggest that a diet high in fat increases the risk of prostate cancer. Studies also suggest that nutrients such as soy isoflavones, vitamin E, selenium, vitamin D and carotenoids (including lycopene, the red color agent in tomatoes and beets) may decrease prostate cancer risk. Vasectomy may be linked to increased prostate cancer rates as well. Workers in industries, such as welding, with exposure to the metal cadmium appear to have a higher than average risk of prostate cancer. Male sex hormone levels also may be linked to the rate of prostate cancer. In addition, some studies have linked increased prostate cancer risk to smoking.

Genetic profile

An estimated 5–10% of prostate cancer is due to a hereditary cause. Among men with early prostate cancer, a hereditary cause is likely in up to a third of cases before age 60, and almost half of men diagnosed at age 55 or less. Studies have found around a twoto three-fold increased rate of prostate cancer in close relatives of men with the disease. Hereditary prostate cancer is likely in a family if there are three cases of prostate cancer in close relatives or three affected generations (either mother’s or father’s side), or two relatives with prostate cancer before age 55.

cancer Prostate

Prostate cancer

•frequent urination (especially at night)

•difficulty starting urination

•inability to urinate

•pain or burning sensation when urinating

•blood in the urine

•persistent pain in lower back, hips, or thighs (bone pain)

•difficulty having or keeping an erection (impotence)

Diagnosis

Although prostate cancer may be very slow-grow- ing, it can be quite aggressive, especially in younger men. When the disease is slow-growing, it may go undetected. Because it may take many years for the cancer to develop, many men with the disease are likely to die of other causes rather than from the cancer.

Prostate cancer is frequently curable when detected early. However, because the early stages of prostate cancer may not have any symptoms, it often remains undetected until the patient goes for a routine physical examination. Diagnosis of the disease is made using some or all of the following tests.

Digital rectal examination (DRE)

In order to perform this test, the doctor puts a gloved, lubricated finger (digit) into the rectum to feel for any lumps in the prostate. The rectum lies just behind the prostate gland, and a majority of prostate tumors begin in the posterior region of the prostate. If the doctor does detect an abnormality, he or she may order more tests in order to confirm these findings.

Blood tests

Blood tests are used to measure the amounts of certain protein markers, such as prostate-specific antigen (PSA), found circulating in the blood. The cells lining the prostate generally make this protein and a small amount can be detected in the bloodstream. However, prostate cancers typically produce a lot of this protein, and it can be easily detected in the blood. Hence, when PSA is found in the blood in higher than normal amounts (for the patient’s age group), cancer may be present. Occasionally, other blood tests also are used to help with the diagnosis.

Transrectal ultrasound

A small probe is placed in the rectum and sound waves are released from the probe. These sound waves bounce off the prostate tissue and an image is created. Since normal prostate tissue and prostate tumors reflect the sound waves differently, the test can be used to detect

The enlarged lymph node in the groin area of this male patient is a sign of prostate cancer. (Photo Researchers, Inc.)

tumors. Though the insertion of the probe into the rectum may be slightly uncomfortable, the procedure is generally painless and takes only about 20 minutes.

Prostate biopsy

If cancer is suspected from the results of any of the above tests, the doctor will remove a small piece of prostate tissue with a hollow needle. This sample is then checked under the microscope for the presence of cancerous cells. Prostate biopsy is the most definitive diagnostic tool for prostate cancer.

If cancer is detected during the microscopic examination of the prostate tissue, the pathologist will “grade” the tumor. This means that the tumor will be scored on a scale of 2-10 to indicate how aggressive the tumor is. Tumors with a lower score are less likely to grow and spread than are tumors with higher scores. This method of grading tumors is called the Gleason system. This is different from “staging” of the cancer. When a doctor stages a cancer, the doctor gives it a number that indicates whether it has spread and the extent of spread of the disease. In Stage I, the cancer is localized in the prostate in one area, while in the last stage, Stage IV, the cancer cells have spread to other parts of the body.

X rays and imaging techniques

X-ray studies may be ordered to determine whether the cancer has spread to other areas. Imaging techniques (such as computed tomography scans and magnetic resonance imaging), where a computer is used to generate a detailed picture of the prostate and areas nearby, may be done to get a clearer view of the internal organs. A bone scan may be used to check whether the cancer has spread to the bone.

The American Cancer Society and other organizations recommend that PSA blood testing and DRE be

cancer Prostate

Prostate cancer

offered to men with at least a 10-year life expectancy beginning at age 50. Men at higher risk for prostate cancer, such as those with a family history of the disease or African American men, may wish to consider screening at an earlier age such as 45. A low-fat diet may slow the progression of prostate cancer. Hence, the American Cancer Society recommends a diet rich in fruits, vegetables, and dietary fiber, and low in red meat and saturated fats, in order to reduce the risk of prostate cancer.

Treatment

The doctor and the patient will decide on the treatment after considering many factors. For example, the patient’s age, the stage of the tumor, his general health, and the presence of any co-existing illnesses have to be considered. In addition, the patient’s personal preferences and the risks and benefits of each treatment method are also taken into account before any decision is made.

Surgery

For early stage prostate cancer, surgery is frequently considered. Radical prostatectomy involves complete removal of the prostate. During the surgery, a sample of the lymph nodes near the prostate is removed to determine whether the cancer has spread beyond the prostate gland. Because the seminal vesicles (the gland where the sperm is made) are removed along with the prostate, infertility is a side effect of this type of surgery. In order to minimize the risk of impotence (inability to have an erection) and incontinence (inability to control urine flow), a procedure known as “nerve-sparing” prostatectomy is used.

In a different surgical method, known as the transurethral resection procedure or TURP, only the cancerous portion of the prostate is removed, by using a small wire loop that is introduced into the prostate through the urethra. This technique is most often used in men who cannot have a radical prostatectomy due to age or other illness, and it is rarely recommended.

Radiation therapy

Radiation therapy involves the use of high-energy x rays to kill cancer cells or to shrink tumors. It can be used instead of surgery for early stage cancer. The radiation can either be administered from a machine outside the body (external beam radiation), or small radioactive pellets can be implanted in the prostate gland in the area surrounding the tumor.

Hormone therapy

Hormone therapy is commonly used when the cancer is in an advanced stage and has spread to other parts of the body. Prostate cells need the male hormone testosterone to grow. Decreasing the levels of this hormone, or inhibiting its activity, may cause the cancer to shrink or stop growing. Hormone levels can be decreased in several ways. Orchiectomy is a surgical procedure that involves complete removal of the testicles, leading to a decrease in the levels of testosterone. Alternatively, drugs (such as LHRH agonists or anti-androgens) that bind to the male hormone testosterone and block its activity can be given. Another method tricks the body by administering the female hormone estrogen. When this is given, the body senses the presence of a sex hormone and stops making the male hormone testosterone. However, there are some side effects to hormone therapy. Men may have “hot flashes,” enlargement and tenderness of the breasts, or impotence and loss of sexual desire, as well as blood clots, heart attacks, and strokes, depending on the dose of estrogen.

Chemotherapy

Chemotherapy is the use of drugs to kill cancer cells. The drugs can either be taken as a pill or injected into the body through a needle that is inserted into a blood vessel. This type of treatment is called systemic treatment because the drug enters the blood stream, travels through the whole body, and kills the cancer cells that are outside the prostate. Chemotherapy is sometimes used to treat prostate cancer that has recurred after other treatment. Research is ongoing to find more drugs that are effective for the treatment of prostate cancer.

Watchful waiting

Watchful waiting means no immediate treatment is recommended, but doctors keep the patient under careful observation. This option is generally used in older patients when the tumor is not very aggressive and the patients have other, more life-threatening illnesses. Prostate cancer in older men tends to be slow-growing. Therefore, the risk of the patient dying from prostate cancer, rather than from other causes, is relatively small.

Prognosis

According to the American Cancer Society, the survival rate for all stages of prostate cancer combined has increased from 50% to 87% over the last 30 years. Due to early detection and better screening methods, nearly 60% of the tumors are diagnosed while they are still confined to the prostate gland. The five-year survival rate for early