Talk:Wilson's disease/Archive 1

Basal ganglia

No mention of the basal ganglia? [1] --David Iberri (talk) 20:32, 29 May 2006 (UTC)

I added a brief mention of the basal ganglia and the Parkinsonian symptoms that result. --David Iberri (talk) 18:32, 30 May 2006 (UTC)

El Salvador

What is the most reliable source for this disease's high incidence in Central America, specifically El Salvador? JFW | T@lk 11:13, 26 June 2006 (UTC)

Still haven't found a good source for the statistic presently mentioned in the article. OMIM makes no mention of it. Perhaps we should remove it. JFW | T@lk 15:55, 28 August 2006 (UTC)

After 1.5 years I think we can safely say that this was a hoax. I have again searched PubMed, Google and OMIM for this, and nothing was found. JFW | T@lk 10:15, 13 January 2008 (UTC)

"Sick euthyroid syndrome"

Is it worth mentioning that this is not "Wilson's thyroid syndrome," - apparently a source of confusion at Talk:Hypothyroidism ? --apers0n 12:00, 29 August 2006 (UTC)

Presentation of symptoms after age 50

In the July 1999 Newsletter of the Wilson's Disease Association there is a story about a case that did not present symptoms until age 58. BellyOption 23:37, 10 September 2006 (UTC)

In the UK we stop getting Wilson screens on liver patients above the age of 45, unless suspicion is high. Is one case (in a non-scientific publication) going to determine the content of this article? JFW | T@lk 23:55, 10 September 2006 (UTC)

The viewpoint on Wilson's is changing somewhat -- we're viewing it more as a rare disease that can present at any time, even though most present before the age of 35. Eve Roberts' AASLD guideline from 2003 started to address this: AASLD guideline. I've got one patient diagnosed in his early 50's. The Michigan group has many patients diagnosed in their late forties and fifties -- Samir धर्म 09:26, 11 September 2006 (UTC)

Gut article

PMID 16709660 - a comprehensive case series looking at diagnosis and prognosis. Waiting for fulltext. JFW | T@lk 01:28, 19 December 2006 (UTC)

There is also a recent seminar in the Lancet (Lancet 2007; 369: 397-408). Presently at home, but will get fulltext at work and edit the article. JFW | T@lk 07:13, 19 February 2007 (UTC)

More on Wilson

doi:10.1053/j.gastro.2007.07.031 - image and short biography. JFW | T@lk 13:12, 30 September 2007 (UTC)

doi:10.1136/jcp.2006.041756 suggests the copper:coeruloplasmin ratio might be useful. JFW | T@lk 10:43, 11 April 2008 (UTC)

PMID 14723607 is a free recent (2004) review. I will preferentially use Ala 2007 but Ferenci may serve as a backup. JFW | T@lk 10:44, 11 April 2008 (UTC)

Given that Ala2007 is a bit low on neurological diagnosis, doi:10.1055/s-2007-971173 may be of additive benefit. JFW | T@lk 11:26, 13 April 2008 (UTC)

PMID 16532467 seems to be looking at genotype-phenotype interaction, but I cannot access this and probably will not. JFW | T@lk 11:28, 13 April 2008 (UTC)

Other copper diseases

We need to mention:

• North American Indian childhood cirrhosis (CIRH1A-related)
• Endemic Tyrolean infantile cirrhosis (OMIM 215600, KRT8 and KRT18-related)
• Idiopathic copper toxicosis ("non-Indian") - OMIM suggests that this has not been linked yet.

These are copper storage diseases distinct from Wilson's that may all lead to childhood cirrhosis. JFW | T@lk 11:16, 11 April 2008 (UTC)

Zinc

Walshe PMC 1442728 indicates that zinc was initially pioneered in the Netherlands. We probably ought to mention Walshe's own role in introducing trien and molybdenum. JFW | T@lk 11:05, 18 May 2008 (UTC)

Done. Now what to do with http://www.whonamedit.com/synd.cfm/1818.html - it seems that Westphal and Strumpell already made some observations, and one report I came across even suggests that they anticipated the role of copper. These observations are not mentioned in most English-language reviews on Wilson's, and I'm a bit hesitant to overemphasise the possible role of these admittedly legendary physicians. JFW | T@lk 13:37, 20 May 2008 (UTC)

It's OK, the Robertson citation covers all bases. I wasn't aware that eight of SAKW's patients had been quoted from the literature! JFW | T@lk 13:58, 20 May 2008 (UTC)

Copper metabolism

I'm doing a section on copper metabolism that could probably be replicated in copper. I'm mostly using DeBie2007, but the perfect source would of course be doi:10.1146/annurev.nutr.20.1.291. The same author has written much on copper metabolism, but none of the papers in question are available free. JFW | T@lk 16:32, 20 May 2008 (UTC)

• Saw the questions regarding hemolytic anemia and thought this might help:

"Within RBCs copper may damage the cell membrane, accelerate oxidation of hemoglobin, and inactivate enzymes of the pentose-phosphate and glycolytic pathways. Which of these abnormalities is responsible for the shortened RBC survival is not known.

.... The release of inorganic copper into the circulation accounts for the occurance of hemolytic anemia in Wilson disease." Wintrobe's Clinical Hematology, 11th Edition, Chapter 38

"Free copper can interfere with glucose metabolism by hexokinase inhibition and alternatively can generate oxidative hemolysis, perhaps by acting as a Fenton reagent." Hoffman: Hematology: Basic Principles and Practice, 3rd Edition.

• SincerelyNomen Nescio^{Gnothi seauton} 17:23, 20 May 2008 (UTC)

BAL

I wasn't aware that BAL was still being used for refractory cases: doi:10.1136/jnnp.2007.139386 (also a beautiful story about keeping an open mind). JFW | T@lk 15:59, 21 May 2008 (UTC)

Still to do

Before I submit this for peer review and WP:GAC:

• Mention that asymptomatic people with evidence of copper overload are still treated -  Done
• Try to fix the copper metabolism image to actually scale properly (may need to upload a small version) -  Done (thumbnailed instead)
• Perhaps an image to illustrate the location of the basal ganglia -  Done
• We need to mention BAL somewhere as a treatment of last resort -  Done
• More information on why neuropsychiatric Wilson's is generally regarded as a poor indication for liver transplant (Ala et al discuss this in fair detail)  Done - Not an awful lot left to say
• We need to list the other inherited copper overload disorders somewhere -  Done - sourced to De Bie

More probably to come. JFW | T@lk 12:04, 22 May 2008 (UTC)

Prevalence

The lead states prevalence as between 1 in 30,000 and 1 in 100,000 people, not sure but think it's be clearer to have one figure e.g. 'between 1 - 4 in 100,000' LeeVJ (talk) 23:43, 26 May 2008 (UTC)

Done. I will try again to get the image to scale nicely. What are the defaults for image sizes? JFW | T@lk 16:41, 27 May 2008 (UTC)

Psych prevalences

The top of ==Signs and symptoms== says 34% with neurological problems, but === Neuropsychiatric symptoms === says "about half". These numbers are not sufficiently similar to make me confident in them.

At the top of ==Signs==, did you calculate those numbers from Table 2? You might want to recalculate them, noting that the fourth column doesn't sum correctly. (18 ≠ 7+10+0) I get 35.5%, 58.4%, and 6.0% (neuro, liver, and none) -- or, with a more reasonable level of precision, given the total n, "about a third, about three-fifths, and a small proportion." WhatamIdoing (talk) 05:56, 29 May 2008 (UTC)

See next entry. JFW | T@lk 08:25, 29 May 2008 (UTC)

Mean ages

I think that the standard deviations are rather large (about ten years) for us to be quite this precise with the mean ages. The "15.5" really means "more or less as a teenager," and the "20.2" means "as a teenager or a younger adult." Could we perhaps change that to something like "a mean age of approximately 15, ±10 years" or "a mean age of 20 (with a standard deviation of about 10 years)" instead?

(I'll leave the question about why the authors used the mean age, instead of the median, for the letters page in Gut.) I've only read through the ==Diagnosis== section and am out of time for now. WhatamIdoing (talk) 05:56, 29 May 2008 (UTC)

The problem of the Merle study is the fact that it's a case series from one catchment area, presumably with specific mutations. That makes the statistics relatively uninteresting (because they might not hold true for patients in the USA, China or elsewhere). I have simply removed all the numbers; we should use Ala and Roberts for the "grander picture". JFW | T@lk 08:25, 29 May 2008 (UTC)

Genetics

In the category of "One of these things is not like the other:"[2]

• The first paragraph in this section says that 30% of patients have a single copy of the mutated gene.
• The last paragraph says that it's (always) autosomal recessive and (always) requires two abnormal copies.

Can we reconcile these somehow? WhatamIdoing (talk) 06:02, 30 May 2008 (UTC)

I like your Sesame Street reference! This may have to do with being able to actually detect mutations. I am not sure if there is actually a small group of patients who are heterozygous but in a way that is severe enough to still cause frank WD; the sources don't mention this possibility, so I am led to be believe that my first statement is true.

Thanks for your ongoing input. JFW | T@lk 06:29, 30 May 2008 (UTC)

Pathophysiology

Just three things to say here:

1. Are fibrosis and cirrhosis really different in this context? (Does the fibrosis appear outside of the liver?) Would it be appropriate to simplify it (them) down to "scar tissue"?
2. The color change on the Copper atom in the image is cool: it goes from "orange" to "green". Is the starting color actually accurate? Does the atom go from Cu¹⁺ to Cu²⁺ (or make other suitable changes)?
3. The bit starting "Wilson's disease is the commonest of a group of diseases..." doesn't really seem to be in the right section. Should it move to ==Related conditions== or perhaps the lead (as part of context setting)? WhatamIdoing (talk) 06:45, 30 May 2008 (UTC)

1. Fibrosis is reversible, cirrhosis is not. I'll try to fix this.
2. The color change is completely arbitrary. In fact, the orange ball is a food bolus, while the green colour was actually intended to be ATP7B carrying the copper. I will clarify it in the caption, and (when I get home) remove the orange ball. To my knowledge, the valence remains unchanged.
3. I will move the other copper toxicity conditions elsewhere.

JFW | T@lk 09:49, 30 May 2008 (UTC)

Irony

Just for the irony of the thing: Drwilson.com. JFW | T@lk 09:49, 30 May 2008 (UTC)

Name Nomenclature

Since all disease names based on a last name have been changed to not include the apostrophe s at the end, shouldn't Wilson's disease be listed as Wilson disease? Although I can't find a direct source for this change, a search in PubMed will show that it is listed as Wilson disease in the majority of the latest articles. Lynx8 (talk) 17:14, 30 May 2008 (UTC)

The change is not universal and seems to happen idiosyncratically. Wikipedia tends to stick with whatever the first author chose, unless there's a really good reason to change, and just create redirects for other possible spellings. See Talk:Down_syndrome#Requested_move for a good example of a very similar debate. WhatamIdoing (talk) 18:03, 30 May 2008 (UTC)

Wrapping up first review

Under ==Treatment==:

• In the case of paradoxical symptom exacerbation, is trien a replacement for penicillamine treatment, or in addition to it? Do symptoms abate under the new regimen?
  •  Done It is a replacement. I have clarified. JFW | T@lk 12:53, 1 June 2008 (UTC)
• Is zinc acetate specifically necessary, or is any normal vitamin/mineral formulation of zinc good enough?
  •  Done Sources don't state this specifically. It seems any zinc will do. JFW | T@lk 12:53, 1 June 2008 (UTC)
• Can zinc treatment be started on day one, or is it delayed until the end of chelation therapy?
  •  Not done Sources don't state whether zinc is taken from diagnosis. I'd prefer to stick with the present version, as I am not certain that zinc will not interfere with the other drugs. JFW | T@lk 12:53, 1 June 2008 (UTC)
• The term side effect is not so commonly hyphenated these days. Is this more common in British English? (It's ultimately unimportant to me, so I didn't change it.)
  •  Done Not sure what happened; I never use a hyphen (except when I do, clearly). JFW | T@lk 12:53, 1 June 2008 (UTC)

From ==Other species==:

• "In other human copper accumulation states..." -- shouldn't that say just "In human copper accumulation states..."?
  •  Done Well, the aim of that study was to see if non-Wilsonian copper accumulation could be attributed to COMM1 mutations. JFW | T@lk 12:53, 1 June 2008 (UTC)

From MEDMOS:

• Genetics and Pathophys usually come before Diagnosis in the usual order of sections. The suggested order is not binding, of course.
  •  Not done I think "diagnosis" must come before going into detail about the disease process. I agree that MEDMOS follows a slightly more logical order (you must know what causes the disease before showing how its presence is demonstrated) but I tend to deviate here. JFW | T@lk 12:53, 1 June 2008 (UTC)

• If you wanted, you could create sections on Screening, Prognosis, and Epidemiology. Screening and epidemiology information is already present in the article. Do you have information about the prognosis? (Note that I consider the creation of what will inevitably be short sections here to be entirely optional.)
  • Screening is not really performed other than case finding; I'm loathe to repeat the old chestnuts about inappropriateness of screening unless "Wilson-Jungner criteria" are met (hey, another Wilson!). My sources are very vague on prognosis, and I can therefore not say much about it. Epidemiology would be a very small paragraph that presently is best integrated with the introduction and with the genetics section. JFW | T@lk 12:53, 1 June 2008 (UTC)

Overall, I think this article looks pretty good -- quite a nice little example of your excellent work. WhatamIdoing (talk) 19:03, 30 May 2008 (UTC)

Thanks for your help! JFW | T@lk 12:53, 1 June 2008 (UTC)

I've reviewed the changes and think it all looks great. The GA reviewer should have an easy time with this one. WhatamIdoing (talk) 20:57, 1 June 2008 (UTC)

OK then, I'll post notes here....GA review

Right. I'll get to it a little later. Just got home. Will add some stuff to start with. Cheers, Casliber (talk · contribs) 07:24, 4 June 2008 (UTC)

• this manifests itself with... (bolded bit redundant) --> this manifests as../ this results in... (take your pick)  Done
• If two carriers both pass on an abnormal gene to a child, this child may develop Wilson's disease. - I'd use the passive here as it aligns the subject of both sentences. Try "If a child inherits the gene from both parents, he or she/they may develop Wilson's disease."  Done
• The prevalence of Wilson's disease is between 1 and 4 in 100,000 people. - you could rewrite this in plainer English using the definition of prevalence.  Done
• A small proportion is identified - is/are with 'proportion', I am confused, why not use 'number' then it is an unambiguous plural...  Done
• Under Liver disease, I would have thought spider naevi were a sign not a symptom, but here they are listed with symptoms...better to say they are found on examination? Maybe there should be a line or two on examination findings here.  Done (I suppose people would notice spider naevi and find them cosmetically unappealing JFW | T@lk 15:33, 4 June 2008 (UTC))
• Wilson's disease may be suspected on the basis of any of the medical conditions mentioned above, or when a close relative has been found to have Wilson's. - change 2nd mention to 'condtion' or something.  Done
• If the liver damage is marked, - say 'pronounced' or 'significant' here. Marked sounds odd when used in this way and not directly next to the noun.  Done
• There is no perfect test for Wilson's disease - 'perfect' sounds odd. Maybe 'There is no perfectly reliable...' or 'totally reliable' or somesuch

I need to sleep now. Wil continue from Liver biopsy tomorrow....zzzzzzzzz

Sleep well Casliber. All your recommendations addressed and marked  Done. Looking forward to more of your stylistic advice! JFW | T@lk 15:33, 4 June 2008 (UTC)

More...

• If all or some other investigations... - bolded bit redundant?  Done
• ..is diagnostic for.. - now this is tricky. As doctors, you and I know this means 'confirms'. I wonder whether it does for laypeople.  Done
• lower levels are possible and the results of all other tests taken together still lead to a formal diagnosis of Wilson's - this is a bit ungainly. A comma after 'possible' is needed here, maybe that will be enough but might still need to be reworded a little for flow.  Done (Rephrased, but agree that it's a tad convoluted. JFW | T@lk 13:22, 5 June 2008 (UTC))
• In the earlier stages of the disease, steatosis (deposition of fatty material) is observed, increased glycogen in the nucleus, and focal areas of necrosis (cell death). - needs reorganizing.  Done (Improved flow of sentence. JFW | T@lk 13:22, 5 June 2008 (UTC))
• In more advanced disease, the biopsy shows changes quite similar to those seen in autoimmune hepatitis, such as infiltration by inflammatory cells, piecemeal necrosis and fibrosis. - could remove bolded bits and just say 'there are' or something.  Done
• In advanced disease, finally, cirrhosis is observed. --> try 'Cirrhosis is seen in advanced (end-stage?) disease.'  Done (Rephrased slightly. JFW | T@lk 13:22, 5 June 2008 (UTC))
• Genetic testing - I guess this section could be expanded - how widely available is the test, how much does it cost (well, cheap or expensive etc.) to flesh out this slim subheading. I was going to say merge with the genetics section, but that doesn't work out so good really.
  • This kind of genetic testing is typically ordered by physicians. Once a patient has been found to carry a mutation, relatives would be counselled to approach their primary care provider who would presumably refer to a local clinical genetics service. My sources are quite vague as to the exact yield (given that Wilson's is a recessive disorder), and I can't see much scope for expanding this section.  Not done JFW | T@lk 13:22, 5 June 2008 (UTC)
    • I must agree with JFW on this. It's more than enough what is written in the Genetic testing section. NCurse _work 18:23, 5 June 2008 (UTC)
• The other members of the group are Indian childhood cirrhosis, endemic Tyrolean infantile cirrhosis and idiopathic copper toxicosis - wow. I had never heard of these. Maybe a line or two - are they all the same gene? different gene? all recessive? etc.
  • Neither had I until I printed out the excellent paper by De Bie et al. Very little is known about these (they may represent the same condition), apart from the fact that ICC is now known to be due to keratin 8 (Online Mendelian Inheritance in Man (OMIM): 148060) or keratin 18 (Online Mendelian Inheritance in Man (OMIM): 148070) mutations. I will quote De Bie about this.  Done JFW | T@lk 13:22, 5 June 2008 (UTC)
• Copper#Biological_role should get a link from somewhere in the article. I figure it needs a line or so on copper's biological role in the body (i.e. it is an essential element). Maybe in pathophysiology section somewhere.
  • I inserted it.  Done NCurse _work 18:23, 5 June 2008 (UTC)
  • I've elaborated a bit more, so the reader does not get the impression that copper is pure evil :-) JFW | T@lk 19:34, 5 June 2008 (UTC)
• If trien is a brand name, should it be capitalized? Or is it just an abbreviation?
  • It's an abbreviation, see Triethylenetetramine.  Done NCurse _work 18:27, 5 June 2008 (UTC)
  • The name is not used universally, so I've removed it. JFW | T@lk 19:34, 5 June 2008 (UTC)
• Regarding dimercaprol - is it via an IV infusion (duration?), or IM injection and what frequency? monthly? twice daily? Is it painful and what are the side effects?
  • It is an intermuscular injection that is given every few weeks. It is indeed painful. I will clarify.  Done
• When writing these things I try and think about impacts on patients. The other issue, is there any genetic councelling? Are sufferers fertile/infertile?
  • There are some paragraphs about genetic counseling in the genetics section. The medical condition itself doesn't cause infertility, but the treatment can. ref. NCurse _work 18:27, 5 June 2008 (UTC)
  • There are reports about infertility and abnormal copper indices with conception after chelation. It is not reported in my main sources and does not seem to be a major issue. Genetic counselling is a highly individual process, and I want to avoid WP:HOWTO, but a sufferer does not typically pass on their disease to their children (chance is about 1:100). JFW | T@lk 19:34, 5 June 2008 (UTC)
• more later. damn, gotta run again

OK, looking good, will pass once these commented on or fixed...Cheers, Casliber (talk · contribs) 00:08, 5 June 2008 (UTC)

Comments processed up to "role of copper". De Bie has a fine section on this. JFW | T@lk 13:22, 5 June 2008 (UTC)

All improvements now done. Thanks for your help, Casliber and NCurse. Hope you are happy to promote, and otherwise I'm quite willing to make further changes to satisfy your trained editorial eyes. JFW | T@lk 19:34, 5 June 2008 (UTC)

(wakes up. rubs eyes)....all good. Cheers, Casliber (talk · contribs) 21:42, 5 June 2008 (UTC)

What a lovely timezone-busting GA review that was! Many thanks again. JFW | T@lk 08:16, 6 June 2008 (UTC)

Suspicious edit

An anon editor changed "about 5%" to "about 6%". I can't get to the source; can someone else double check this? WhatamIdoing (talk) 18:21, 6 October 2008 (UTC)

Changed it back. Thanks. JFW | T@lk 23:37, 6 October 2008 (UTC)

New Section needed

Needs a section on 'Prognosis' - Eg. If you get the psychiatric symptoms can these be reversed or is the damage done permanent?

Also I am not convinced that liver transplant can be classified as a 'cure'. It is a genetic condition so wouldn't the same problem still exist with copper being deposited in the brain? Cure is also not a good word to use when it comes to genetic conditions as you still have the bad genes even when you control the symptoms. —Preceding unsigned comment added by 41.213.126.5 (talk) 21:20, 13 April 2009 (UTC)

The sources seem to indicate that chelation would improve neuropsychiatric symptoms. At the same time, penicillamine has a reputation for occasionally worsening symptoms. There is no numerical data as to what proportion of patients improves.

A liver transplant would be a cure if the main problem is liver disease. Firstly, it removes the main site of copper overload, and secondly it introduces normal copper homeostasis by providing the recipient with a liver containing wild type ATP7B. You are correct that if other organs have been affected by copper overload (eg renal tubular acidosis or hypoparathyroidism), one can only really speak of a cure if these problems are reversible. JFW | T@lk 22:30, 13 April 2009 (UTC)

Lancet

PMID 19700008 - case report on mutational analysis. Must read. JFW | T@lk 14:44, 9 September 2009 (UTC)

External link

I would lean toward removing the external link "Wilson's disease at Who Named It?", as the linked page contains only an exceedingly brief (10 sentences), non-vetted summary of the condition. However, I note that the linked page says Wilson's was "First described by Friedrich Theodor von Frerichs (1819-1885) in 1854". Frerich's work is cited as

F. T. von Frerichs:

Klinik der Leberkrankheiten.

2 volumes and atlas. Braunschweig, F. Vieweg u. Sohn, 1858-1861. The description of progressive familal hepatolenticular degneration is in volume 2, pp. 62-64.

I don't see Frerichs mentioned in our article; any credence to this claim? Second opinion on the usefulness of the external link? Maralia (talk) 03:13, 24 November 2009 (UTC)

The historical section is based on the Robertson 2000 article, which is peer-reviewed and more reliable. WhoNamedIt is not always 100% reliable (some entries are a bit cryptic) but freely available and otherwise an interesting resource. JFW | T@lk 21:03, 24 November 2009 (UTC)

Updating

I've just discovered that just after I brought this article to GA status the AASLD published a new guideline. It might help reviewing this and updating the article with any changes doi:10.1002/hep.22261

On the subject of neurologic Wilson's, PMID 17390257 may be useful. JFW | T@lk 17:30, 11 May 2011 (UTC)

The new EASL guideline is here: doi:10.1016/j.jhep.2011.11.007. JFW | T@lk 09:47, 21 October 2012 (UTC)

Great resource! I note that the abstract of those guidelines does contain these depressing statements, "Unfortunately, there is not a single randomized controlled trial conducted in Wilson’s disease which has an optimal design. Thus, it is impossible to assign a high or even a moderate quality of evidence to any of the questions dealt with in these guidelines." Nonetheless, it's important to know when more evidence is needed. -- Scray (talk) 14:05, 21 October 2012 (UTC)

Gene therapy

Not ready for prime time but worth watching: gene therapy for Wilson's in an animal model doi:10.1038/gt.2011.186 JFW | T@lk 11:14, 23 April 2013 (UTC)