$Unique_ID{BRK04333} $Pretitle{} $Title{Wilson's Disease} $Subject{Wilson's Disease Hepatolenticular Degeneration Lenticular Degeneration, Progressive Chorea, Sydenham's Cirrhosis, Primary Biliary Heavy Metal Poisoning Levine-Critchley Syndrome Huntington's Disease Tourette Syndrome Cerebral Palsy } $Volume{} $Log{} Copyright (C) 1985, 1986, 1990, 1991, 1992 National Organization for Rare Disorders, Inc. 26: Wilson's Disease ** IMPORTANT ** It is possible that the main title of the article (Wilson 's Disease) is not the name you expected. Please check the SYNONYMS listing to find the alternate name and disorder subdivisions covered by this article. Synonyms Hepatolenticular Degeneration Lenticular Degeneration, Progressive Information on the following diseases can be found in the Related Disorders section of this report: Chorea, Sydenham's Cirrhosis, Primary Biliary Heavy Metal Poisoning Levine-Critchley Syndrome Huntington's Disease Tourette Syndrome Cerebral Palsy General Discussion ** REMINDER ** The Information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Wilson's Disease is a rare genetic disorder characterized by excess copper stored in various body tissues, particularly the liver, brain, and corneas of the eyes. Later developments include liver (hepatic) disease and central nervous system dysfunction. Early diagnosis and treatment may prevent serious long-term disability. Symptoms Wilson's Disease usually begins with hepatic (liver) or neurologic disturbances, or both. Symptoms of liver dysfunction usually appear after 6 years of age. Jaundice causes a yellow discoloration of the skin, mucous membranes and the sclera of the eyes (membranes that line the eye). Vomiting may also occur. Neurologic symptoms are usually first seen between the ages of 12 and 32 years and are characterized by drooling, difficulty speaking and poorly articulated words (dysarthria). Other neurological symptoms may include difficulty when swallowing (dysphagia), lack of coordination, tremor, spasticity, muscle rigidity and double vision. Other symptoms of Wilson's Disease may include kidney stones, joint disorders and abnormalities of the heart (cardiomyopathy). It is believed that a sudden release of copper from the liver may cause an acute crisis in some patients due to the sudden rapid breakdown of red blood cells (hemolysis). The Kayser-Fleischer ring is an important symptom that eventually appears in the eyes of patients with Wilson's Disease, and especially in patients with neurologic involvement. This ring is a rusty-brown deposit in the corneas of the eyes that may not be present until the later stages of Wilson's disease. Neurological signs and symptoms that may appear in the late stages of Wilson's Disease include decreased cognitive abilities and behavioral disturbances. Joint and bone involvement may include a thinning of the bones (osteoporosis) and the appearance of bony outgrowths (osteophytes) at large joints. There may be reduced spinal and extremity joint spaces. Kidney involvement may include renal tubular damage. The psychiatric manifestations of Wilson's Disease vary widely from patient to patient. These symptoms may be confused with other psychiatric disorders, ranging from depression to schizophrenia. Accurate diagnosis is essential as medications that are commonly given for such disturbances (phenothiazines) can aggravate the neurologic and psychiatric symptoms of Wilson's Disease. The side effects of these drugs may appear similar to symptoms of Wilson's Disease. Most patients with the psychiatric symptoms of Wilson's Disease also have neurologic symptoms and Kayser-Fleischer rings in the corneas of their eyes. In adolescent females, menstruation may not begin until the disease is treated. This is due to the general disturbances in metabolism caused by Wilson's Disease. Causes Wilson's Disease is inherited as an autosomal recessive genetic trait. The defective gene that prevents the liver from adequately excreting copper in the bile has been located on chromosome 13 at position q14. Symptoms develop due to the gradual over-accumulation of copper in the body. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If one receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is twenty-five percent. Fifty percent of their children will be carriers, but healthy as described above. Twenty-five percent of their children will receive both normal genes, one from each parent, and will be genetically normal. Affected Population Wilson's Disease is a rare disorder that affects males and females in equal numbers. The disease is found in all races and ethnic groups. Wilson's Disease occurs in approximately 1 in 100,000 people worldwide. There are about 2,000 diagnosed cases in the United States. Many cases are misdiagnosed, however, usually as mental illness, and the true incidence may be higher. Related Disorders Symptoms of the following disorders can be similar to those of Wilson's Disease. Comparisons may be useful for a differential diagnosis: Sydenham's Chorea is an acute, usually self-limited disorder that occurs after about 5 to 10 percent of cases of rheumatic fever. The disorder typically begins with jerky, uncontrollable, non-repetitive muscle movements on one or both sides of the body. Patients develop rapid, involuntary movements that can affect the manner or style of walking, arm movements and speech. Clumsiness and facial grimacing are common. (For more information on this disorder choose "Sydenham's Chorea" as your search term in the Rare Disease Database). Primary Biliary Cirrhosis is a chronic, progressive disease of the liver thought to be related to abnormalities in the immune system. The initial symptoms of this disorder usually include persistent, generalized itching, dark urine, pale stools and jaundice. Eventually, excessive amounts of copper accumulate in the liver and fibrous or granular hardening occurs in the soft tissue of the liver. (For more information on this disorder, choose "Primary Biliary Cirrhosis " as your search term in the Rare Disease Database). Heavy Metal Poisoning is generally caused by industrial exposure to a variety of toxins such as copper, aluminum, arsenic or mercury. Depending of the type and duration of exposure, the injury may occur in the lungs, nervous system, the skin or digestive system. The symptoms of the poisoning vary according to the type of metal that was involved in the overexposure. These include headache, nausea, dizziness, painful joints and muscles, delirium, seizures and a wide range of other symptoms. (For more information on these disorders, choose "Heavy Metal Poisoning " as your search term in the Rare Disease Database). Levine-Critchley Syndrome is a very rare genetic disorder of the neuromuscular and blood systems. Abnormal blood cells (acanthocytosis) are produced and there is a wasting away (atrophy) of muscles. The major symptom of this disorder is uncontrolled rapid muscular movements (amyotrophic chorea). Initially there are subtle involuntary movements (tics) of the face, mouth, and tongue. These slowly progress to severe, uncontrolled, rapid motions (chorea) of the trunk and limbs. Approximately 50 percent of people with Levine-Critchley Syndrome have seizures. (For more information on this disorder, please choose "Levine-Critchley" as your search term in the Rare Disease Database). Huntington's Disease (Huntington's Chorea) is an inherited, progressively degenerative neurological disorder. Initially there are personality changes and rapid jerky muscle movements that are involuntary. In time speech and memory become impaired and involuntary muscle movements become more frequent and pronounced. As Huntington's Disease progresses there is a further loss of cognitive abilities and dementia. The symptoms of this disorder usually begin during adulthood generally after the age of forty. (For more information on this disorder choose "Huntington" as your search term in the Rare Disease Database.) Tourette Syndrome is a neurologic movement disorder that is characterized by repetitive motor and vocal tics. The first symptoms during childhood are usually rapid eye blinking or facial grimaces. Symptoms may also include involuntary movements of the extremities, shoulders, face and voluntary muscles. Some people with Tourette Syndrome may vocalize involuntarily; these may be inarticulate sounds or words. Tourette Syndrome is not a progressive or degenerative disorder; symptoms tend to be variable and follow a chronic waxing and waning course. Onset is usually begin before the age of 16. (For more information on this disorder, choose "Tourette" as your search term in the Rare Disease Database.) Cerebral Palsy is a neuromuscular disorder that is the result of an injury to the brain during early development or at birth. The major symptom of this disorder is a lack of muscle control and coordination. Cerebral Palsy is not a progressive disorder. Generally infants may exhibit developmental delays during the first or second year and may have muscle weakness and abnormal muscle tone. The coordination and speech difficulties associated with Wilson's Disease can resemble the symptoms of Cerebral Palsy. (For more information on this disorder, choose "Cerebral Palsy" as your search term in the Rare Disease Database.) Therapies: Standard Wilson's Disease is routinely treated with the drug D-Penicillamine. This drug causes the excretion of copper into the urine. Pyrimidine Hydrochloride (Vitamin B6) is usually prescribed to counteract a side effect of penicillamine that can make the patient deficient in Vitamin B6. Treatment must be continued throughout life to avoid abnormal accumulation of copper. However, some patients cannot tolerate long-term therapy with penicillamine. The orphan drug Trien (brand name Cuprid) was approved by the FDA for treatment of Wilson's Disease in 1985. The drug is manufactured by Merck, Sharp and Dohme. Cuprid is an effective therapy for those Wilson's Disease patients who cannot tolerate penicillamine. Physical therapy and speech therapy can be helpful for Wilson's Disease patients with neurological involvement. Liver transplants have been successful in cases of severe liver damage. A low copper diet is often advised. Chocolate, nuts and shell fish are usually high in copper and should not be eaten in excess. Diet information can be obtained from the Wilson's Disease Association. Genetic counseling will be of benefit for patients and their families. Therapies: Investigational The orphan drug Zinc Acetate is being tested as a maintenance therapy to treat Wilson's Disease. Zinc acetate is a common nutritional substance; however, it must be taken in certain doses at specific times during the day to affect copper metabolism. Therefore, careful monitoring by a physician is necessary to assure effectiveness on Wilson's Disease patients. Zinc acetate is manufactured by Lemmon Co., 650 Catarhill Road, Sellersville, PA 18960. For more information, please contact: George J. Brewer, M.D. University of Michigan Medical School Medical Science #MU708 Box 0618 University of Michigan Ann Arbor, MI 48109-0618 Investigational studies are underway to determine the effectiveness of ammonium tetrathiomolybdate as a possible treatment for Wilson's Disease. This agent is being used for initial rapid "decoppering" of patients with this disorder. Further studies are necessary to determine the long-term safety and effectiveness of this treatment. This disease entry is based upon medical information available through November 1992. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Wilson's Disease, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Wilson's Disease Association P.O. Box 75324 Washington, DC 20013 (703) 636-3014 American Liver Foundation 998 Pompton Ave. Cedar Grove, N.J. 07009 (201) 857-2626 The United Liver Foundation 11646 West Pico Blvd. Los Angeles, CA 90064 (213) 445-4204 (213) 445-4200 Children's Liver Foundation 14245 Ventura Blvd. Sherman Oaks, CA 91423 (818) 906-3021 NIH/National Institute of Neurological Disorders & Stroke (NINDS) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5751 (800) 352-9424 For Genetic Information and Genetic Counseling Referrals: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References THE METABOLIC BASIS OF INHERITED DISEASE, 6th Ed., Scriver, Beaudet, Sly, and Valle; McGraw-Hill; 1989. Pp. 1416-1421. MENDELIAN INHERITANCE IN MAN, 10th Ed.: Victor A. McKusick, Editor: Johns Hopkins University Press, 1992. Pp. 1756-1757. CECIL TEXTBOOK OF MEDICINE, 19th Ed.: James B. Wyngaarden, and Lloyd H. Smith, Jr., Editors; W.B. Saunders Co., 1990. Pp. 1132-1133. WILSON'S DISEASE, S.E. Woods; Am Family Physician (July 1989; 40(1)): Pp. 171-178. WILSON'S DISEASE: CURRENT STATUS, J.C. Yarse et al.; Am J Med (June 1992; 92(6)): Pp. 643-654. PATHOPHYSIOLOGY AND TREATMENT OF WILSON'S DISEASE, R.M. Tankanow; Clin Pharm (Nov 1991; 10(11)): Pp. 839-849.