There are small amounts of copper in many things we eat, and, normally, the body knows how to get rid of the excess. But when a genetic defect renders the body incapable of processing this mineral, there are many negative effects.
As the copper starts to build up, it may affect either the liver or nervous system. George Brewer, MD, emeritus professor of human genetics and internal medicine at the University of Michigan explains this rare problem called Wilson's disease.
What is Wilson's disease?
Wilson's disease is an inherited disease that causes the accumulation of copper in the body. The disease generally presents in teenagers or young adults and it develops as either a liver disease or a neurologic abnormality—about half are seen to have neurological effects and about half have problems with the liver.
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The neurological effects occur when the copper accumulation affects the parts of the brain that coordinate movement; they're not affecting the strength of muscles, but rather the coordination of muscles. Speech may be affected, as well as swallowing. Small motor movements may also be very clumsy. There is often tremor or shakiness as part of a movement disorder. Another aspect of the neurological disease is dystonia, where some muscle groups tighten up, causing a limb or the head, for example, to get pulled into abnormal positions.
The disease can also affect the liver, causing hepatitis-like symptoms, in which the patient may be jaundiced, or yellow-colored. If Wilson's disease is caught later on, it may cause cirrhosis, or fibrosis, of the liver. Occasionally, it will present as acute liver failure. Usually this happens in younger people, age 15 or 20 or so. Suddenly, there's an acute liver failure and the liver is so damaged that the only thing that will save the patient's life is transplantation.
Who is at risk for inheriting the disease?
It's recessively inherited, meaning both parents either have Wilson's disease or are carriers of the abnormal gene that causes the disease. And both parents must have at least one copy of the gene for the child to inherit the disease.
When does someone start to show symptoms of the disease?
In Western countries, the most common age of onset is 21 years of age, but the age of onset is quite broad, ranging all the way from 15 to 45 for those with neurologic problems. The average liver presentation tends to be a little bit younger.
What are the symptoms of Wilson's disease?
If the disease is going to show up neurologically, very often an isolated tremor will develop, and then the other symptoms of a movement disorder may begin. But the first thing that is noticed may be speech problems, trouble talking, slurring of words. About half of the patients who present neurologically have previously had depression or bizarre behaviors. It seems that areas of the brain that control emotions are often affected by this disease.
If the patient's liver is affected, it will show up as either jaundice, cirrhosis or liver failure.
How is Wilson's disease diagnosed?
There are two screening tests for Wilson's disease: 24-hour urine copper and a Kaiser-Fleischer ring examination in the eye. The 24-hour urine copper test is done by a physician and directly measures the amount of copper being excreted by the body, while the Kaiser-Fleischer ring needs to be done by an ophthalmologist, who examines the eye with a slit lamp. When someone has Wilson's disease, copper rings form in the cornea. These rings are almost always present when the disease is neurological in nature, and they are almost never there for any other reason.
If the patient has hepatitis, a doctor would normally check for a viral cause for the hepatitis. If this test turns up negative, and the hepatitis patient is in this younger-age group, they should always be screened for Wilson's disease. Remember, these patients don't have the corneal rings as often as the other patients, so a 24-hour urine copper is a better screening test for these patients.
Now, if the screening tests look positive, it is sometimes followed up by a liver biopsy, which is invasive, but a very reliable final test for Wilson's disease
How is Wilson's disease treated?
There are four drugs that are used to treat Wilson's disease. Penicillamine has been around the longest, and because it was the only treatment option for a long period of time, it's the one that most doctors know about. However, while it is effective, it has a lot of side effects. If the patient has the neurologic disease, it is very important that penicillamine not be used: it aggravates neurologic symptoms in about half the patients, and half of those never recover. So, there is a one in four risk of inducing additional, permanent brain damage.
The second drug called trientine works in the same way that penicillamine does-both of these drugs are called chelators; they bind copper and cause its excretion in the urine. Trientine has less toxicity than penicillamine, and has about a 22 percent risk of worsening neurologic symptoms, because it acts sort of like penicillamine, but less aggressively.
Then there is zinc, which acts by blocking the absorption of copper. It's a very effective maintenance therapy. Zinc, in my opinion, is too slow-acting for the patient who presents with an acute illness.
For the liver presentation, we have used a combination of trientine and zinc for about four months and then transition to one or the other as maintenance therapy. Both are effective maintenance therapies, but we tend to favor zinc because it has somewhat less toxicity.
And then there is a drug that is being developing called tetrathiomolybdate (TM). While it's not on the market yet (TM may be available in about a year), it has become the treatment of choice for the patient who has neurological problems. TM is given for about sixteen weeks and then patients are transitioned to maintenance therapy with zinc.
Are there any dietary changes a person should make?
For a long time, a low-copper diet was something all doctors recommended. And it turns out that most of the recommended dietary changes were wrong. We've measured the copper in all of the foods that dieticians traditionally have warned these patients against-such as chocolate, beans or mushrooms—and they're not dangerously high in copper.
The only two foods that we restrict in patients are liver and shellfish. Liver is very high in copper, while shellfish is intermediately high. After we get a patient stabilized on maintenance therapy, we'll allow them to have one meal a week of a shellfish, but they probably shouldn't have more than that.
Patients should have their drinking water checked to make sure it isn't dangerously high in copper. We find that about 5 to 10 percent of samples, particularly well-water samples around the United States, are high in copper.
How effective is therapy?
Once a patient is on an effective therapy, their symptoms should never get worse. The recovery of the neurologic function is usually pretty good; however, it depends a little bit on how severe the patient was affected at the time treatment was started. We can control the copper within a couple of weeks, but then the brain has to repair itself, which takes about two years to complete. So by the end of two years, any recovery that's going to take place has happened.
It's a similar process in the liver, although a little more rapid. In most patients, all liver function will return to normal over about a six- to twelve-month period. But it still has underlying cirrhosis, so the reserve of liver tissue is less. The patient will probably have complications from that.
What advice do you have for people with Wilson's disease?
The biggest problem with this disease is the failure to recognize it by the doctors out there. Then, we see patients that are much more damaged than they would have been if it been picked up earlier, so early recognition is really important.