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Wilsonís Disease

Wilsonís disease is a disease which is marked by defective copper metabolism. You wind up with far too much copper in your liver, your central nervous system, and also in the kidney. The liver and the central nervous system are the two that really present to you most often, in terms of clinical symptoms. Now on the lab tests, what are you going to see? The serum copper is low and the serum ceruloplasmin, which is the carrier protein, is low. You are going to do a 24 hour urine copper. Thatís going to be really high. And you are going to have your local, friendly hepatologist do a liver biopsy and you will note that the liver copper content is quite elevated, and thatís the diagnostic test. So if you are worried about Wilsonís disease, get someone to do a liver biopsy.

The presentation can be all over the map. It can present as acute fulminant hepatitis. If it does, the tip-off is that these children have acute hemolytic anemia in association with their fulminant liver failure. If you see that combination, think Wilsonís disease until proven otherwise. They may present as a chronic active hepatitis, cirrhosis, portal hypertension, variceal bleeding. They may be totally asymptomatic with just a moderately elevated transaminitis. Some of these children do present with the neurologic symptoms more than the liver symptoms and they can be very subtle. Changes in personality, school performance, behavior characteristics that the parents come in and say, "this just isnít anything like the child I used to know." Be very aware of that. The Kayser-Fleischer rings, the brown pigment around the iris, is always talked about in the books.

The treatment for Wilsonís disease depends on when your diagnose is, which is why early diagnosis is essential. If there is no cirrhosis you are going to treat these patients with chelating agents.

However, if fully developed cirrhosis has already occurred, or they are presenting to you in fulminant liver failure, you have no other option but liver transplantation. There is another reason why diagnosis is so very important, because once you identify the index case youíve got to screen those family members because you may be sitting on an asymptomatic sibling who you can treat very successfully with chelating agents.

Alpha 1-antitrypsin deficiency. Turning away from the infections, the metabolic causes of chronic liver disease in children, by far and away the most common is alpha 1-antitrypsin deficiency. And if you remember, this is, generally speaking, associated with the ZZ phenotype. Occasionally you see it with some of the other phenotypes like MZ, but for purposes of keeping life simple, itís the ZZ phenotype, generally speaking. As I said before, these children may have presented in infancy with a high bilirubin which completely went away, the diagnosis may never have been made until they come into your office or in to the hospital in childhood and theyíve already developed signs of portal hypertension.

Cystic fibrosis. You normally think about this as being a disease involving the lungs. Interestingly, cirrhosis with portal hypertension can occur in cystic fibrosis, generally presenting in mid or older age children. Sometimes the liver disease is much more important than the lung disease in these children, and they may also present with portal hypertension and already developed cirrhosis. If theyíve got portal hypertension, you try to shunt some of these children if they are big enough.

Tyrosinemia. We heard about this in the infant age range. How about in children as a cause of chronic hepatitis? Tyrosinemia is an autosomal recessive disease. As we said, in infancy it is a fulminant presentation. In childhood, a chronic presentation. A very important thing about tyrosinemia in children is its association with hepatocellular carcinoma. Twenty-seven percent of children by their second birthday will already have HCC. So thatís why you really have to transplant these children, generally speaking, before the age of two in order to avoid this devastating complication. The other two systems that are involved are the central nervous system - neurologic crises, which can actually look like acute porphyria can occur.

Making the diagnosis, we talked about. You measure the succinylacetone in the urine. In terms of treatment, you manipulate the diet to get rid of the offending precursor proteins and now there is an interesting alternative. A chemical agent, shortened to NTBC, and the importance of this is it actually halts tyrosine degradation so that you donít form the toxic metabolite, which is succinylacetone. This can actually be very effective, particularly in the infants, but what we donít think it does is we donít think it stops the progression to hepatocellular carcinoma.