Sunday, July 26, 2009

The Wilson's Disease "Bible" (Part II)

Understanding how to treat Wilson's Disease is the key. The rest of the book discusses management and treatment. The last chapter discusses the history and future of Wilson's. That was my favorite part to read. I had no idea how recent testing and treatment had been made available. It was definitely a bitter-sweet moment when I realized that if my oldest son would have had Wilson's Disease (being born in 1996), the specific genetic test that ulitimately diagnosed my daughter would not have been available!!

Chapter 5 explains management and what is important and what is not. This chapter answered a lot of questions for me. He suggests that "a low copper diet" is not necessary...especially after patient is on anticopper drugs. He also cautions that drinking water is actually more of a risk, particularly during the initial therapy. How does the doctor choose the drug? This chapter answers that question. What about monitoring? That is also answered. He covers diet and how there are only two things that he cautions patients about: liver and shellfish. He explains that "we have remeasured the copper level in most of the important foods, and find that the content of copper in foods listed in previous tables were too high..." I thought that was quite interesting. He suggests testing your drinking water and if the copper level is more than 0.1 PPM (parts per million) then getting a filter or finding alternative water sources. Unfortunately, in our area the copper level in our water is above the recommended level for my daughter so we got a Brita filter. FYI: Brita filters (the ones that mount on the faucet) DO filter copper.

Chapter 6 discusses the treatment of patients with liver disease. This is the type my daughter could have had if she were not treated, and so I was especially curious to read about the types of symptoms to look out for and laboratory results that pertain to this manifestation of WD. He goes over liver transplant and that was quite scary for me to read. He stresses that doctors should NOT do a liver transplant as long as medical therapy is doing the job. He DOES explain when liver transplant SHOULD be done and even offers a recommended anticopper therapy for those patients awaiting a liver transplant.

Chapter 7 covers treatment of patients with neurologic and/or psychiatric disease. He cautions doctors against using penicillamine therapy for these type of patients. He says that symptoms will actually get worse in about 50% of patients.... and worse yet, the risk of permanent worsening is about 25%! Dr. Brewer suggests using Tetrathiomolybdate for these patients and explains in depth why.

Chapter 8 discusses maintenance therapy. Maintenance therapy is what happens after you get rid of the copper toxicity and continues for the rest of the patient's life. He covers the objectives and methods of maintenance therapy. Dr. Brewer definitely prefers zinc therapy and explains in detail all about it. He offers graphs and lots of information that support his findings. This chapter is perfect for any patient who wants to know how zinc works and how to monitor it throughout his/her lifetime.

Chapter 9 was the chapter that I anticipated the most. It covers the therapy for presymptomatic, pediatric, and pregnant patients. Since my daughter is a pediatric patient and will one day (hopefully) want to have children, I anxiously read through this chapter hopeful that she would have the opportunity to bear children. According to Dr. Brewer there is hope for my daughter. He emphasizes the need to continue anticopper therapy throughout the pregnancy and that with the zinc acetate there is less risk of teratogenic (disruptive to the development)effect on the fetus than penicillamine (which used to be the only choice for patients). This is something that she will definitely have to prayerfully decide. According to Dr. Brewer zinc is the safest of all the drugs. The biggest danger is the mother deciding to halt her medication out of fear of harm to her unborn.... that would definitely be tragic.

In Chapter 10 Dr. Brewer discusses the risk factors during maintenance therapy and the prognosis of Wilson's patients. The biggest risk, believe it or not, is POOR COMPLIANCE! This is especially true in younger patients and/or asymptomatic ones. He says, "It is always shocking to me that compliance is not almost perfect in this disease, given the availability of an effective, oral, non-toxic medication, such as zinc, and given the severity of the alternative." That basically sums it up. However, he goes over some of the things that CAN happen to patients when certain symptoms do not improve and how accidents can be another issue. This is especially true in patients with neuroligical symptoms. For example, a patient with severe depression might commit suicide. That is something that doctors need to be aware of. His final sentence in this chapter is my favorite one: "The bottom line that should be conveyed is thta if you're going to have a genetic disease, this is a good one to have because it is so treatable."

Chapter 11 covers the disease pathogenesis and genetics. Although I HATE what this disease does, I have to admit that the genetics and the disease itself is rather fascinating. I never realized how important copper truly was until I had to read all about it. Why don't doctors test it more often? That is definitely a question to ask. There are still many things we do not know about the genetic defect of the ATP7B gene and how many mutations there are. According to this chapter, over 170 mutations have now been described!! There is an interesting table that shows the mutations in various populations. It is suggested that depending on the mutation that determines the age of onset of the disease and how it manifests itself. Perhaps one day they will be able to find a way to test for that. I am sure it is not too far in the future.

Chapter 12 discusses disease pathology. This chapter answers the question of how excess copper causes damage to cells and organs. This is the chapter that will enlighten you to how important copper is and why too much and not good. This explains why the liver is the primary organ that is affected. The next organ that usually affected is the brain since it is the next most sensitive organ. He discusses the female reproductive system, skeletal system, kidneys, eyes, and heart. It is important to note that Dr. Brewer states: "In the past, the disease was likely more advanced when diagnosed. This probably accounts for many of the pathological and clinical differences reported in the past compared to more modern experience. Today we almost never see the kinds of renal, skeletal, and cardiac abnormalities that were commonly reported two or three decades ago."

The final chapter is one that covers the history and milestones of Wilson's Disease. It is interesting to see how the discovery of the disease came about. It all started with Dr. Wilson who saw several patients with liver disease and then Kayser and Fleischer observed corneal copper deposits in the eyes of another group of patients. All of this happened in the early 1900's. Eventually the copper connection was made and the disease was discovered. It is interesting to note that in 1977 Dr. Brewer observed that zinc therapy in sickle cell anemia produced copper deficiency. This is what led to the idea of using zinc for therapy. It wasn't until 1993 that the genetic cause of Wilson's was discovered. In 1997 zinc therapy was finally approved by the FDA. One thing that was interesting to note was that just because a patient has the harmful mutation of the ATP7B gene, that doesn't mean that the person will reach the full penetrance of the clinical disorder. Therefore it is not ever 100%. Some patients might actually have a milder expression of the gene. Dr. Brewer also mentions that he had two patients who were vegetarians and adequately controlled the disease. He says that the mechanism of this is that copper is less thoroughly absorbed from vegetable foods than from meat. He cautions that he does not recommend a vegetarian diet as a therapeutic approach because it may not work in some patients. His main point is that diet can be a factor in age of onset and other manifestations.

The most important part of the book is the challenges that Dr. Brewer expresses. He basically says that if a doctor doesn't even consider Wilson's in a patient then it won't be diagnosed. If it isn't diagnosed then it won't be treated. If a patient is not treated.... the end is not good. However, the future looks bright. There are already new and better treatment options. The screening methods are improving. I know that there will be advancements in the field of genetics that will help with testing and screening. As we better understand the role of ATP7B in regulating copper then we can better understand how mutation of this gene intereferes with this function. That will ultimately lead to more patients being diagnosed and less ending up with tragic endings.
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The future definitely looks bright!
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