Wilson disease
Wilson disease, also known as hepatolenticular degeneration, is a genetic disorder that affects copper metabolism, leading to the accumulation of toxic levels of copper in the body, particularly in the liver and brain. This autosomal recessive condition arises from a defect in a gene located on chromosome 13 responsible for copper transport. Symptoms typically manifest between the ages of ten and forty, and can include liver damage (such as hepatitis, cirrhosis, and acute liver failure), neurological issues (including tremors, slurred speech, and dystonia), and psychiatric disturbances (like mood swings, depression, and psychosis). A distinctive feature of Wilson disease is the Kayser-Fleischer rings, which are deposits of copper in the eye, often present in patients with neurological or psychiatric symptoms.
Effective diagnosis involves tests such as measuring ceruloplasmin levels and urinary copper excretion, alongside a slitlamp examination to identify the characteristic rings. The gold standard for diagnosis is a liver biopsy showing elevated copper levels. Treatment focuses on reducing copper accumulation and can include chelating agents like penicillamine or trientine, zinc to block copper absorption, and in severe cases, liver transplantation. Early diagnosis and intervention are crucial for managing this chronic condition and improving patient outcomes.
Wilson disease
ALSO KNOWN AS: Hepatolenticular degeneration
ANATOMY OR SYSTEM AFFECTED: Brain, liver, nervous system, psychic-emotional system
DEFINITION: An inherited disease of abnormal copper metabolism, leading to copper accumulation and toxicity in the liver and brain
CAUSES: Genetic defect in copper metabolism
SYMPTOMS: Liver damage (hepatitis, cirrhosis, liver failure); neurologic problems (slurred speech, tremor, rigidity in extremities, dystonia, seizures, mental changes, transient periods of coma); psychiatric abnormalities (behavioral changes, moodiness, depression, psychosis)
DURATION: Chronic
TREATMENTS: Chelating agents (penicillamine, trientine), zinc, tetrathiomolybdate, liver transplantation
Causes and Symptoms
Wilson disease is an autosomal recessive disorder of copper metabolism, resulting in excess copper accumulation and toxicity in the body. The gene in Wilson disease is located on chromosome 13 and codes for a copper-transporting protein. The normal mechanism of elimination of excess copper in humans is excretion of extra copper in the bile for loss in the stool. The genetic in this disease causes defective, reduced excretion of copper into the bile by the liver. The resultant excessive copper accumulation in the liver and causes liver damage and as well as psychiatric abnormalities.
Wilson disease typically manifests itself between the ages of ten and forty, although it may also appear in earlier childhood as well as later in life. Typical signs and symptoms are related to damage to the liver and brain. Liver involvement in Wilson disease may vary from hepatitis or chronic cirrhosis to acute liver failure. Neurologic symptoms and signs often involve areas of brain that control movement. Patients may have slurred speech, tremor and rigidity in the extremities, and dystonia, a syndrome of sustained muscle contractions causing abnormal postures or movements. Other symptoms include seizures, mental changes, and transient periods of coma. Psychiatric abnormalities may also be prominent and the initial presentation. Behavioral changes include impaired school performance, labile moods, depression, and psychosis.
Useful tests for Wilson disease include ceruloplasmin, twenty-four-hour urine copper, and slitlamp examination for Kayser-Fleischer rings. Blood ceruloplasmin is usually low in Wilson disease, although approximately 10 to 25 percent of patients will have a normal value. Urinary copper values are typically elevated in symptomatic patients. Kayser-Fleisher rings, which are caused by copper deposits in the of the eye, can be detected reliably only by slitlamp microscopy examination. They are almost always seen in patients with neurologic or psychiatric symptoms but may not be present in patients with symptoms related to liver damage. The gold standard for diagnosis in Wilson disease is liver biopsy, which reveals an elevated amount of copper in the liver.
Treatment and Therapy
Given the diverse initial presentations of Wilson disease, early diagnosis is often difficult. It is important, however, because effective treatments exist. Treatment is aimed toward the prevention of copper accumulation, the of copper absorption through the promotion of its excretion in the urine or bile, or a combination of these mechanisms. Pharmacologic treatments include penicillamine and trientine, two drugs that act by removing copper (chelating agents); zinc, which blocks copper absorption; and tetrathiomolybdate, which is experimental. Liver can be helpful in the patient with end-stage liver disease.
Bibliography
Brewer, George J. Wilson’s Disease: A Clinician’s Guide to Recognition, Diagnosis, and Management. Boston: Kluwer Academic, 2001.
Hoogenraad, Tjaard U. Wilson’s Disease. Philadelphia: W. B. Saunders, 1996.
"NINDS Wilson Disease Information Page." National Institute of Neurological Disorders and Stroke, June 14, 2012.
Parker, James N., and Philip M. Parker, eds. The 2002 Official Patient’s Sourcebook on Wilson’s Disease. San Diego, Calif.: Icon Health, 2002.
Rosenblum, Laurie, and Michael Woods. "Wilson Disease." Health Library, Apr. 26, 2013.
Rowland, Lewis P., Timothy A. Pedly, and H. Houston Merritt, ed. Merritt’s Neurology. 12th ed. Philadelphia: Lippincott Williams & Wilkins, 2010.
Schilsky, M. L. “Diagnosis and Treatment of Wilson’s Disease.” Pediatric Transplantation 6 (2002): 15–19.
"Wilson's Disease." Mayo Clinic, 2 Dec. 2023, www.mayoclinic.org/diseases-conditions/wilsons-disease/symptoms-causes/syc-20353251. Accessed 8 Apr. 2024.
"Wilson Disease." MedlinePlus, 11 July 2022, medlineplus.gov/genetics/condition/wilson-disease/#. Accessed 8 Apr. 2024.
"Wilson Disease." National Digestive Diseases Information Clearinghouse (NDDIC), Apr. 30, 2012.