What is Wilson disease? Wilson disease is a genetic disorder that prevents the body from getting rid of extra copper. A small amount of copper obtained from food is needed to stay healthy, but too much copper is poisonous. In Wilson disease, copper builds up in the liver, brain, eyes, and other organs. Over time, high copper levels can cause life-threatening organ damage. Pathophysiology and clinical features of Wilson disease Wilson disease is an autosomal recessive inherited disorder of copper metabolism resulting in pathological accumulation of copper in many organs and tissues.
ATP7B is the gene product of the Wilson disease gene located on chromosome 13 and resides in hepatocytes in the trans-Golgi network, transporting copper into the secretory pathway for incorporation into apoceruloplasmin and excretion into the bile. Mutations of the gene result in impaired trafficking of copper in and through the hepatocytes. More than 200 mutations of Wilson disease gene were found, the most common ones being H1069Q (in Europe) and R778L (in Asia). Wilson disease may present under a variety of clinical conditions, commonly as liver and/or neuropsychiatric disease.
The pathogenesis of hepatic and neurologic Wilson disease is a direct consequence of copper accumulation. Presence of copper causes oxidative stress resulting in cell destruction. The diagnosis of Wilson disease requires a combination of a variety of clinical symptoms, biochemical tests, and detection of gene mutations, which are the basis of a score proposed by a group of international experts. Initial treatment for symptomatic patients should include a chelating agent (penicillamine or trientine). Treatment of presymptomatic patients or maintenance therapy can also be accomplished with zinc.
Who gets Wilson disease? People who get Wilson disease inherit two abnormal copies of the ATP7B gene, one from each parent. Wilson disease carriers, who have only one copy of the abnormal gene, do not have symptoms. Most people with Wilson disease have no known family history of the disease. A person’s chances of having Wilson disease increase if one or both parents have it. What causes Wilson disease? Wilson disease is caused by a buildup of copper in the body. Normally, copper from the diet is filtered out by the liver and released into bile, which flows out of the body through the gastrointestinal tract.
People who have Wilson disease cannot release copper from the liver at a normal rate, due to a mutation of the ATP7B gene. When the copper storage capacity of the liver is exceeded, copper is released into the bloodstream and travels to other organs—including the brain, kidneys, and eyes. What are the symptoms of Wilson disease? Wilson disease first attacks the liver, the central nervous system, or both. A buildup of copper in the liver may cause ongoing liver disease. Rarely, acute liver failure occurs; most patients develop signs and symptoms that accompany chronic liver disease, including.
• swelling of the liver or spleen • jaundice, or yellowing of the skin and whites of the eyes • fluid buildup in the legs or abdomen • a tendency to bruise easily • fatigue • problems with speech, swallowing, or physical coordination • tremors or uncontrolled movements • muscle stiffness • behavioral changes • anemia • low platelet or white blood cell count • slower blood clotting, measured by a blood test • high levels of amino acids, protein, uric acid, and carbohydrates in urine • premature osteoporosis and arthritis Kayser-Fleischer rings result from a buildup of copper in the eyes and are the most unique sign of Wilson disease.
They appear in each eye as a rusty-brown ring around the edge of the iris and in the rim of the cornea. The iris is the colored part of the eye surrounding the pupil. The cornea is the transparent outer membrane that covers the eye. How is Wilson disease diagnosed? Wilson disease is diagnosed through a physical examination and laboratory tests. During the physical examination, a doctorwill look for visible signs of Wilson disease.
A special light called a slit lamp is used to look for Kayser-Fleischer rings in the eyes. Kayser-Fleischer rings are present in almost all people with Wilson disease who show signs of neurologic damage but are present in only 50 percent of those with signs of liver damage alone. Laboratory tests measure the amount of copper in the blood, urine, and liver tissue. Most people with Wilson disease will have a lower than normal level of copper in the blood and a lower level of corresponding ceruloplasmin, a protein that carries copper in the bloodstream. In cases of acute liver failure caused by Wilson disease, the level of blood copper is often higher than normal.
A 24-hour urine collection will show increased copper in the urine in most patients who display symptoms. A liver biopsy—a procedure that removes a small piece of liver tissue—can show if the liver is retaining too much copper. The analysis of biopsied liver tissue with a microscope detects liver damage, which often shows a pattern unique to Wilson disease. Genetic testing may help diagnose Wilson disease in some people, particularly those with a family history of the disease. Wilson disease can be misdiagnosed because it is rare and its symptoms are similar to those of other conditions.
How is Wilson disease treated? Wilson disease requires lifelong treatment to reduce and control the amount of copper in the body. Initial therapy includes the removal of excess copper, a reduction of copper intake, and the treatment of any liver or central nervous system damage. Pregnant women should take a lower dose of d-penicillamine or trientine hydrochloride during pregnancy to reduce the risk of birth defects. A lower dose will also help reduce the risk of slower wound healing if surgical procedures are performed during childbirth. Zinc, administered as zinc salts such as zinc acetate (Galzin), blocks the digestive tract’s absorption of copper from food.
Zinc removes copper too slowly to be used alone as an initial therapy for people who already have symptoms, but it is often used in combination with d-penicillamine or trientine hydrochloride. Zinc is safe to use at full dosage during pregnancy. Maintenance therapy begins when symptoms improve and tests show that copper has been reduced to a safe level. Maintenance therapy typically includes taking zinc and low doses of either d-penicillamine or trientine hydrochloride. Blood and urine sho uldbe monitored by a health care provider to ensure treatment is keeping copper at a safe level. People with Wilson disease should reduce their dietary copper intake. They should not eat shellfish or liver, as these foods may contain high levels of copper.
Other foods high in copper— including mushrooms, nuts, and chocolate—should be avoided during initial therapy but, in most cases, may be eaten in moderation during maintenance therapy. People with Wilson disease should have their drinking water checked for copper content and should not take multivitamins that contain copper.
If the disorder is detected early and treated effectively, people with Wilson disease can enjoy good health.
Refrences “Wilson’s Disease – Symptoms and Treatment. ” Medical Base. N. p. , 1 Jan. 2014. Web. . <http://www. wilsondisease. org/>. “American Liver Foundation – Wilson Disease. ” American Liver Foundation. N. p. , 4 Oct. 2011. Web. . <http://www. liverfoundation. org/abouttheliver/info/wilson/>. “Wilson Disease: MedlinePlus – U. S. National Library of Medicine. ” Medline plus. N. p. , n. d. Web. . <http://www. nlm. nih. gov/medlineplus/wilsondisease. html>.