Wilson's Disease

Neutralized by Zinc

At age 22, the woman weighed 69½ pounds, consumed 700 calories a day, appeared depressed, didn't menstruate, chattered incessantly and worried constantly about everything and anything.

Her doctors suspected an eating disorder, so they admitted her to a hospital at the National Institutes of Health in Bethesda, Maryland, and began to run some tests.

Everything checked out normally until they looked at her liver. There the doctors found that the woman had almost 15 times the normal amount of copper tucked away, a sure sign that she had Wilson's disease, a condition in which various body tissues are slowly poisoned by copper.

Sunflower Eyes and Shaking Limbs

Copper is a nutrient that is required by all cells, most notably for the development of healthy nerves, connective tissue and the dark pigment in hair and skin. Everyone needs a little copper. In someone with Wilson's disease, however, a genetic error allows the metal to build up to toxic levels in the brain, liver, kidneys and eyes. The astronomical amounts that accumulate can result in impaired mental ability, dementia and liver failure.

Fortunately, the disease is rare, preventable and treatable. It occurs in about 30 of every 1,000,000 people, generally somewhere between the ages of 10 and 40 and most often among Eastern European Jews and their descendants.

Depending on where toxic levels of copper are accumulating, symptoms can range from malaise, fatigue, tenderness over the liver and perhaps low-grade fever--which together may seem to indicate a viral infection or acute hepatitis--all the way to eating disorders, the cessation of menstruation, shaking limbs and "sunflower cataracts," which are green, yellow or brown rings around the corneas.

"The biggest problem is recognition of the disease," says pioneering researcher George Brewer, M.D., professor of human genetics and internal medicine at the University of Michigan Medical School in Ann Arbor. "Many cases go unrecognized because the disease masquerades as, say, hepatitis or cirrhosis of the liver caused by alcohol."

Complicating recognition is the fact that symptoms frequently evolve over time rather than appearing all at once. "Instead of developing obvious neurological complications, for example, many people will have behavioral abnormalities for several years," explains Dr. Brewer. "They can become depressed, and they usually lose the ability to focus mentally. So if they're in school, their grades will drop. Or if they have jobs, they'll start to not perform as well. They'll become temperamental. They may become suicidal, and they can become exhibitionists.

"Often these behaviors are attributed to drug abuse, because you have people who have been normal and they sort of go off the deep end. Their spouses often leave during this period," he says.

The Blessing of Zinc

Fortunately, Wilson's disease is both preventable and treatable with zinc, according to Dr. Brewer.

In a series of studies at the University of Michigan, Dr. Brewer and his colleagues found that zinc induces formation of metallothionein, a substance that grabs on to any copper it can find and holds the copper in intestinal cells until they are sloughed off and excreted with other intestinal waste.

"The intestinal cells, like cells on the surface of your skin, turn over fairly rapidly," explains Dr. Brewer. "They have about a six-day life span. So when they slough into the intestines, they take the copper with them. It then goes out into the stool."

But zinc is not the first thing that doctors reach for when Wilson's disease is diagnosed. "Zinc is kind of leisurely acting for somebody who is symptomatic," says Dr. Brewer. "So we've developed a new drug called tetrathiomolybdate, a compound that works very nicely in the initial treatment of people with brain symptoms. We use it for eight weeks, and then we transition to zinc.

"For people with liver disease," he continues, "we use a combination of another drug, trientine hydrochloride (Syprine), and zinc. The trientine helps flush out the copper fairly rapidly."

Once on zinc-only therapy, a person with Wilson's disease is home free. "You're not trying to get rid of all of the copper in your body," says Dr. Brewer. "Copper is an essential nutrient, and without copper, people die. So what you're doing with zinc therapy is reducing the excessive load of copper and preventing it from reaccumulating."

That's why you can eat a normal diet. "The only two foods we ask people not to eat are liver, which is loaded with copper, and shellfish, which have intermediately high amounts," adds Dr. Brewer.

Sopping Up Copper

How much zinc does it take to sop up the extra copper in your body?

A study conducted by Dr. Brewer at the University of Michigan indicated that 150 milligrams of zinc a day, taken as three separate 50-milligram doses, each at least an hour before or after a meal, provides optimum copper removal. Because zinc can be toxic in such a high amount, it's important that you be under medical supervision while using this therapy.

Taking zinc with meals negates the mineral's effect. "If zinc is taken with a food, it's almost like not taking it, because it gets bound with material in the food and doesn't do much," says Dr. Brewer. "But if you split it away from food, as little as 25 milligrams will have a detectable effect on copper balance."

And that's also why people who do not have Wilson's disease should not take large amounts of zinc, adds Dr. Brewer. Since it takes a fairly small amount of zinc to have an effect on copper levels in the body, taking more than the Daily Value of zinc (15 milligrams) could easily make you copper-deficient within two to three weeks.

Preventing the Problem

Zinc also has the ability to prevent the onset of symptoms in people who have inherited the aberrant gene but have not yet developed any symptoms. Unfortunately, the only way to detect the possibility that you might have Wilson's disease before symptoms appear is to have it hit a brother or sister.

That's why siblings of those with Wilson's disease should have their urine monitored by their family physicians on a regular basis for elevated levels of copper, says Dr. Brewer. The odds are one in four that they will develop the disease at some time in their lives.

"Wilson's disease is an autosomal recessive disease," Dr. Brewer says. "That means the affected person has two doses of the abnormal gene that triggers the disease. The parents are obligatory carriers, but since each parent has only one dose, they will be completely normal."

Fortunately, even children who have inherited the disease will be completely normal, too--once they're put on zinc, says Dr. Brewer.