Familial Transthyretin Amyloidosis
 

My students and I have done a fair bit of work on the basic science of the TTR amyloidoses, including a number of published papers.

Familial amyloid polyneuropathy (FAP) is usually associated with the L55P mutation (very aggressive) and sometimes the V30M (less aggressive) mutation in the TTR gene.

As the article says, FAP is an autosomal dominant condition which means that somebody only needs to inherit one copy of the mutant gene to get it. It is very uncommon, mainly affecting kindreds from Sweden and Portugal.

In practical terms, what this means is that somebody who is at risk of FAP will have a strong family history of it (sporadic amyloidogenic mutations in the TTR gene are extremely rare).

If there is no family history then there is nothing to worry about.

Thanks, Kiwi. My neuro will soon test me for it. I'm not too concerned that I have it, but my uncle and father are simultaneously exhibiting some issues that overlap, though no neuropathy I think. I just skimmed the article but will sit down and read it when I get a chance tomorrow. Given that you're working on this, perhaps I can ask you this in advance: how accurate will the genetic testing that my neuro will do be? Should I also push for a fat pad biopsy?

My own worry is that it could be Amyloidosis, but perhaps not familial. Thanks in advance.

Genetic screening for L55P or V30M is very easy and accurate to do. It would take my lab (we are not a commercial set-up) about a week. I wouldn't worry about a fat pad biopsy.

Neuropathy can be associated with amyloidogenic proteins other than TTR. The information in this link might give you something to think about and discuss with your neurologist; http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3531896/.

Thanks, Kiwi. I've read that among other things a few months ago when Amyloidosis was suspected. If I'm not mistaken, the piece I posted, which I'm now going to read in detail, notes many other mutations and not just those two, no? Is it that those two are the most common?

Yes, it can, and my main concern is primary, or even secondary (though to a lesser degree), but my neuro seems to think familial, I'm not sure quite why. We'll see.

Regarding the fat pad biopsy, why do you think I shouldn't concern myself with one? If you mean for familial, I understand, though I could have a mutation that has yet to be recorded. For the non-genetic ones, it's the surest way to diagnose, about 80% or higher precision, short of biopsying the organ itself.

Thanks again for your input and assistance.

"Regarding the fat pad biopsy, why do you think I shouldn't concern myself with one?"

Oops, my mistake - I don't know much about about amyloidosis from a clinical perspective.

After a bit more reading I agree with you that a fat pad biopsy would be a good plan.

Thanks, Kiwi. Good to know. Now to find someone to do it short of going to the Mayo Clinic or Boston.

If you read this, I'm curious whether it's possible that they find a new mutation with me and just don't know. I'm quite ignorant when it comes to genetic testing, so I'm basically wandering if when they test me they'll first notice a mutation, and then have to inquire whether said mutation is a dangerous mutation. Thanks.

I am not too knowledgeable about this but aren't there other non hereditary forms of Amyloidosis? Owing to a frequently high total protein in full blood count and a widespread small fibre neuropathy and history of Rheumatoid - my rheumatologist requested a Bence Jones urine test to check for Amyloidosis or Multiple Myeloma. I got a bit freaked out when I found out what he was looking for but had a phone call late on Christmas Eve saying it was negative. Hugely relieved but have been wondering what is making my protein high, also evidenced by paired oligloclonal bands in my spinal fluid and serum blood.

Do you happen to know whether it's still possible to have Amyloidosis or MM with a negative Bence Jones?

Yes, there are three general types, I believe: primary, secondary (both of which are not hereditary) and familial. I don't know about your last question, perhaps someone more knowledgeable than I can offer information, but I can say that urine tests are not accurate for diagnosing amyloidosis. The most accurate test that's minimally invasive but quite accurate, upwards of 90%, is a fat pad biopsy. This can detect amyloid deposits. The most accurate is to biopsy the organ tissue itself, if a particular organ, say the kidney, is suspected, but that's obviously much more invasive. I hope this helps.

Yes thanks. I'm guessing that they think that I'd be much sicker now if I had Amyloidosis but I was very sick indeed for a lot of last year. I hope you get answers for yourself sooner than I have David. Mat