Wilson's disease

Wilson's disease
Definition
Wilson's disease is an inherited disorder that causes too much copper to accumulate in your liver, brain and other vital organs. Wilson's disease shows up in a variety of different ways, but the disease can remain silent for years.
Copper plays a key role in the development of healthy nerves, bones, collagen and the skin pigment melanin. Normally, copper is absorbed from your food, and any excess is excreted through bile — a substance produced in your liver.
But in people with Wilson's disease, copper isn't eliminated properly and instead accumulates, possibly to a life-threatening level. Left untreated, Wilson's disease is fatal. When diagnosed early, Wilson's disease is treatable, and many people with the disorder live normal lives.
Symptoms
In people with Wilson's disease, copper begins accumulating in the liver immediately after birth, but signs and symptoms rarely occur before the age of 5 or 6. The disease almost always becomes apparent before age 30, but Wilson's disease symptoms sometimes appear much later in life.
The stored copper can damage many organs and tissues, but the liver and central nervous system are most often affected:
 Liver problems. Because copper first accumulates in the liver, most people initially have signs of liver damage, including abdominal pain and yellowing of the skin and whites of the eyes (jaundice). Later in the disease, anemia or the vomiting of blood can occur. Sometimes the disease progresses without any obvious symptoms until you develop cirrhosis — irreversible scarring of the liver that affects its ability to carry out vital functions. At this point, signs and symptoms may include swelling in your abdomen (ascites) or legs (edema) and an enlarged spleen.
 Neurological problems. Up to about one-third of people with Wilson's disease have neurological signs and symptoms, such as tremors, muscle spasms, unsteady walk, difficulty speaking and drooling.
 Behavioral or psychological problems. Wilson's disease can cause abrupt personality changes and inappropriate behavior. Children with the disease are sometimes misdiagnosed as having behavioral problems because they behave erratically or perform poorly in school.
 Eye, kidney and bone problems. Many people with Wilson's disease, even those who don't have other signs and symptoms, develop a distinctive, golden brown pigmentation around their corneas (Kayser-Fleischer ring). Caused by copper deposits, Kayser-Fleischer rings are often discovered during a routine eye exam. Wilson's disease can also interfere with the kidneys' filtering function and lead to weak, brittle bones (osteoporosis). The disease can also lead to kidney stones.
 Causes
 A number of foods, especially liver, shellfish, nuts, avocados and mushrooms, contain abundant amounts of copper. When you eat copper-containing foods, the copper is absorbed by your small intestine, bound to circulating proteins in your blood and delivered to your liver. Any copper your body doesn't use is carried away by bile, a substance produced in your liver that helps digest fats.
 Gene defect causes copper buildup
In Wilson's disease, a genetic mutation of chromosome 13 affects ATP7B, a protein that helps transport copper into the bile. ATP7B is also involved in incorporating copper into ceruloplasmin, a protein that carries the mineral through your bloodstream. The defects in the ATP7B gene mean that copper isn't eliminated properly, and instead builds up in your liver, where it can cause serious and sometimes irreversible damage. In time, excess copper spills out of your liver and begins accumulating in and harming other organs, especially your brain, eyes, kidneys and joints.
 Although some ATP7B mutations occur spontaneously, most are passed from one generation to the next. Wilson's disease is inherited as an autosomal recessive trait, which means that to develop the disease you must inherit two copies of the defective gene, one from each parent. If you receive only one abnormal gene, you won't become ill yourself, but you're considered a carrier and can pass the gene to your children. Wilson's disease itself is rare, but as many as one in 100 people has one defective ATP7B gene.
Risk factors
If both parents are carriers of one abnormal Wilson's gene, they have a 25 percent chance of having a child with two normal genes, a 50 percent chance of having a child who also is a carrier, and a 25 percent chance of having a child with two recessive genes who will develop the disease. These chances are the same in each pregnancy.

For that reason, experts recommend that all children and siblings of people with Wilson's be tested for the disease. In addition, your doctor may want to test you if you had a parent or grandparent who died of unexplained liver disease.

Complications
Wilson's disease can increase your risk of bone fractures and of serious infections and may greatly impair kidney function. But one of the most serious complications is liver damage, which may be so severe that only a liver transplant can prolong life. If not treated, Wilson's disease is fatal.

Other complications may include:
Damage to the central nervous system. This may cause uncontrollable repetitive movements, stiffness, speech problems, and the loss of the ability to function at work or at home. Coordination also may be affected, resulting in clumsiness and awkwardness in mobility.
Psychological problems. The most common psychological complications associated with Wilson's disease include mood swings, depression, inappropriate behavior, agitation, loss of memory and confusion — problems that sometimes may be mistaken for signs of Alzheimer's disease.
Treatments and drugs
The goal of Wilson's disease treatment is twofold:
 To remove excess copper
 To prevent copper from building up again
Once treatment starts, the disease stops progressing and many signs and symptoms improve. But some problems may take time to resolve. Other problems — especially liver scarring and certain neurological or psychological symptoms — may not be completely reversible. Untreated Wilson's disease is always fatal.
Doctors usually prescribe one of the following medications to help treat Wilson's disease:
 Penicillamine (Cuprimine, Depen). Chelation therapy is the use of chemicals to bind to and remove metals and minerals. Penicillamine was the first copper chelating drug approved for use in Wilson's disease. It works by binding to copper and creating a water-soluble complex that's excreted in your urine. Although it's an effective treatment, penicillamine can cause serious side effects, including skin problems, bone marrow suppression, worsening of neurological symptoms and birth defects.
Penicillamine shouldn't be taken by people with kidney disease or those who are allergic to penicillin. If you do chose to be treated with the drug, you'll also need to take vitamin B-6 supplements because penicillamine can cause a serious deficiency of this vitamin.
 Trientine (Syprine). Another chelating agent, trientine also binds to copper and helps eliminate it from your body. Because it's less toxic than penicillamine, many doctors consider it a first-line therapy, especially in people with liver or neurological symptoms. Trientine also binds to iron, and taking iron supplements can reduce the drug's effectiveness.
 Zinc acetate. Working differently from chelating drugs, the mineral zinc helps prevent copper from being absorbed in your stomach and small intestine. Zinc has few side effects, but it's slower acting than are penicillamine and trientine and so is usually considered an initial treatment only for pregnant women, for people without symptoms or liver damage, or for those who can't tolerate stronger medications.
Doctors may switch people taking penicillamine or trientine to zinc once their symptoms improve, or zinc may be used in combination with penicillamine for people with neurological symptoms.
 Tetrathiomolybdate. This copper-binding agent is being studied in clinical trials.
If you have Wilson's disease, you'll need to continue taking a copper-reducing medication for life. Your doctor may also recommend that you avoid tap water containing more than 100 micrograms of copper per liter, copper-containing vitamin and mineral supplements, and foods high in copper such as:
 Liver
 Shellfish
 Mushrooms
 Nuts
 Chocolate
 Dried fruit
 Dried peas, beans and lentils
 Avocados
 Bran products
Liver transplantation
For people with severe cirrhosis, fulminating hepatitis or other serious liver disorders, a liver transplant may be the only option.