Re: 's Disease

[Guest guest]

> I think it's important to recognize that PSC is associated with

copper accumulation, much as in 's disease:

My son's dr didn't even mention this! He just said " it looks like

Wyatt has 's disease, too " , then went on to explain about the

copper, discuss the next copper level test, and referred us to his

Dietician for the low/no copper diet. I haven't found much in my own

research yet (basic single, two page websites for info, plus posting

here). Thank you, for this information. I'm calling my son's

dr back to ask why he thinks copper in the liver means 's.

> suggested abnormal hepatic copper metabolism in this

disease...Virtually all patients had at least one abnormal copper

test. In advanced histologic stages of primary sclerosing

cholangitis, progressively higher mean levels of hepatic and urinary

copper were found. In the liver, mean copper content (in micrograms

per gram dry weight) in disease stages I and II was 147 +/- 36 (mean

+/- SE); in stage III (fibrosis), 302 +/- 68; and in stage IV

(cirrhosis), 379 +/- 69. In the urine, mean copper excretion (in

micrograms per 24 h) in stages I and II was 72 +/- 14 (mean +/- SE);

in stage III, 100 +/- 14; and in stage IV, 207 +/- 30.

Where do you find such wonderfully detailed information (and so

quickly, too)? You are amazing.

> Higher hepatic and urinary copper levels at initial evaluation were

associated with decreased survival during a median follow-up period

of 2.6 yr: patients with hepatic copper greater than 250micrograms/g

dry wt and urinary copper excretion greater than 200 micrograms/24 h

at initial evaluation had an 18-mo survival of less than 60%.

My son is stage 1, so even if his copper levels are high, this

wouldn't apply to him, correct?

>We conclude that abnormal copper metabolism is a universal feature

of primary sclerosing cholangitis, that hepatic copper accumulates

and urinary copper excretion increases as the disease progresses, and

that the hepatic copper concentration and the 24-h urinary copper

determination are useful prognostic indicators in this disease.

> So a high hepatic or urinary copper level does not necessarily

mean " 's disease " .

This makes me question how much my son's dr really knows about PSC.

Again, thank you.

> Strictly, 's disease is caused by a mutation in a gene

encoding the copper-transport protein, ATP7B.

From what I have researched so far (which isn't too much yet), it

takes two carrier parents to get 's.

Is there benefit to following the low copper diet for elevated copper

levels due to PSC or is it only beneficial when you have 's?

--Meghan, mom to Wyatt (PSC & UC 1/07: FAP 8/01: ?'s -I'm full

of doubt over)

[Guest guest]

Hi Meghan;

> Where do you find such wonderfully detailed information (and so

> quickly, too)?

Since our son was diagnosed with PSC and UC, we've spent over 3.5

years studying the literature, and have built a searchable database

with over 53,000 abstracts and 26,000 full papers. So it's easy to

find obscure facts. The paper I cited was from 1985 and is one such

obscure fact.

It is still plausible that Wyatt might have 's disease;

elevated copper level should always prompt further tests for 's

disease [see for example the article on " 's Disease (The

Cleveland Clinic) " that we have linked to 2nd from the bottom on the

psc-literature www Resources page]:

http://www.psc-literature.org/wwwres.htm

> My son is stage 1, so even if his copper levels are high, this

> wouldn't apply to him, correct?

I think it would depend upon the level of copper observed.

> This makes me question how much my son's dr really knows about

PSC.

As I mentioned, the fact that copper is elevated in PSC is a pretty

obscure fact, and it may not be known to everyone working with PSC

patients. How can any doctor keep up with the literature these days,

let alone remember stuff from 22 years ago? Please don't be too hard

on your son's Dr.

> From what I have researched so far (which isn't too much yet), it

> takes two carrier parents to get 's.

Yes, that's correct, but heterozygous (with only 1 copy of the mutant

gene) can also exhibit abnormal copper tests, see sections

from " 's Disease (The Cleveland Clinic) " :

" WD is transmitted from generation to generation by autosomal

recessive inheritance. Only homozygotes for this disorder who inherit

disease-specific mutations2,3 of both alleles of the 's disease

gene may go on to manifest clinical evidence of the condition. Such

individuals have been described in many different races and number

about 1 in 30,000 of the worldwide population. As will be described

later, particular mutations are found more frequently in specific

populations or ethnic groups with varying phenotypic expression in

certain of these mutations. However, it is known that heterozygotes

with a mutation of a single allele do not develop disease although

they may show varying degrees of abnormality in serum copper markers. "

" WD should be considered and excluded in any individual between

childhood and age 40 years who has unexplained hepatic, neurologic,

or psychiatric disease (Table 3). In particular, it should be

considered in children or young adults with atypical extrapyramidal

or cerebellar motor dysfunction, neuropsychiatric disease, elevated

aminotransferases, or other features of acute or subacute liver

disease and with unexplained non-immune-mediated hemolysis. In these

circumstances, WD must be considered whether or not there is a family

history of liver or neurologic disease. In most cases, the diagnosis

can be confirmed on the basis of clinical and biochemical evaluation

without the need for liver biopsy. "

> Is there benefit to following the low copper diet for elevated

> copper levels due to PSC or is it only beneficial when you have

> 's?

I don't know the answer to this. I would think it might be

appropriate, again depending upon the level of copper observed. Our

son has not been tested for copper recently. I think we may ask for

this test at next blood work. If the level of copper is high, we

might suggest [in consultation with his Doctor] restricting dietary

intake of foods rich in copper (organ meats, nuts, chocolate, and

shellfish). I've read that copper chelation agents like penicillamine

have been used in 's disease, but based on the following paper

I would not put our son on penicillamine (I'd prefer to try a dietary

approach):

Aliment Pharmacol Ther. 2006 Dec;24(11-12):1535-44.

Systematic review and meta-analysis: D-Penicillamine vs. placebo/no

intervention in patients with primary biliary cirrhosis--Cochrane

Hepato-Biliary Group.

Gong Y, Klingenberg SL, Gluud C; Cochrane Hepato-Biliary Group.

Copenhagen Trial Unit, Centre for Clinical Intervention Research, H:S

Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

ygong@...

BACKGROUND: D-Penicillamine is used for patients with primary biliary

cirrhosis due to its ability to decrease hepatic copper and modulate

the immune response. The results on effects of D--penicillamine in

randomized-clinical trials of primary biliary cirrhosis patients are

inconsistent. AIM: To systematically evaluate the benefits and harms

of D-penicillamine for patients with primary biliary cirrhosis.

METHODS: We have performed a systematic review with meta-analyses of

randomized-clinical trials to evaluate the effects of D-penicillamine

for primary biliary cirrhosis. The primary outcomes are mortality and

mortality or liver transplantation. We analysed the data by fixed-

effect and random-effect models. RESULTS: Seven randomized trials

including 706 patients were analysed. d-Penicillamine was without

significant effects on mortality (RR 1.08, 95% CI: 0.82-1.43, P =

0.56), mortality or liver transplantation (RR 1.11, 95% CI: 0.74-

1.68, P = 0.62), pruritus, liver complications, progression of liver

histological stage and liver biochemical variables. D--Penicillamine

significantly decreased serum alanine aminotransferase activity

(weighted mean difference -45 IU/L, 95% CI: -75 to -15, P < 0.05) and

led to significantly more adverse events (RR 4.18, 95% CI: 1.38-

12.69, P = 0.01). CONCLUSION: D-Penicillamine did not appear to

reduce the risk of mortality or morbidity, and led to more adverse

events in patients with primary biliary cirrhosis. PMID: 17206942.

Best regards,

Dave

(father of (21); PSC 07/03; UC 08/03)

[Guest guest]

> Since our son was diagnosed with PSC and UC, we've spent over 3.5

years studying the literature, and have built a searchable database

with over 53,000 abstracts and 26,000 full papers. So it's easy to

find obscure facts. The paper I cited was from 1985 and is one such

obscure fact.

It is still plausible that Wyatt might have 's disease;

elevated copper level should always prompt further tests for

's disease [see for example the article on " 's Disease

I want to thank you, , for finding and sharing the information

you did with me today (so quickly). I wasn't able to reach my son's

dr again, but I've made an appt for Wyatt/us for a 2nd opinion on all

the conditions (not doubting all of them, but wanting another

physician to look over all the lab and test results and find out what

treatments they suggest in comparison --that sort of 2nd opinion).

We're going to UCSF for this even before the next appt with Wyatt's

local dr is set for.

I've also found a family counselor who is also a genetecist

specializing in helping families dealing with medical issues (the

staff geneticist at UCSF led me to her).

We plan to set an appt with a Nutritionist at UCSF as well.

You've been such a great help, so informative and knowledgeable. I

really appreciate that and hope to be able to do the same for someone

else myself someday ( " pay it forward " ).

Thank you again, . Your son has a super dad.

>Please don't be too hard on your son's Dr.

Oh, lol, don't worry. He's been a very good dr so far, although he

has been showing some kinks in the coil lately. He dx Celiac and

Hashimoto's in my niece where no one else did before him. She'd been

very ill and undergoing tests with various drs before he stepped in.

It made life so much better for her (she also has Juvenile Diabetes

and a seizure disorder). He is insistent, however, on only speaking

to my husband and I with our son present. We, are insistent on

seeing him privately for some of our questions and concerns, ones we

feel would only serve to frighten our son if asked in front of him.

That has been a tricky situation for us lately and is not typical of

how he has been in the past with us.

>I've read that copper chelation agents like penicillamine have been

used in 's disease, but based on the following paper I would

not put our son on penicillamine (I'd prefer to try a dietary

approach):

I agree. I've read up on that one myself -bad side effects. The

zinc acetate/zine salt sound good to me instead.

One last time... thank you so much, .

Meghan, mom to Wyatt (12yo/ PSC & UC 1-07/ FAP 8-01/ ?'s?)

[Guest guest]

Hi Meghan;

> I want to thank you, , for finding and sharing the information

> you did with me today (so quickly).

I'm pleased to be able to help in any small way.

> We're going to UCSF for this even before the next appt with Wyatt's

> local dr is set for.

It's a small world. is interviewing at UCSF today! Wish him luck.

Best regards,

Dave

(father of (21); PSC 07/03; UC 08/03)

[Guest guest]

> It's a small world. is interviewing at UCSF today! Wish him

luck.

That would be wonderful for him; I definitely wish him well with the

interview!

-Meghan, mom to Wyatt (PSC/UC 1/07, FAP 8/01, ?WD?)

[Guest guest]

> is interviewing at UCSF today! Wish him luck.

>

>

Best wishes to from me.