Saturday, November 30, 2013

Article Review (2006) - Hereditary fibrinogen A alpha-chain amyloidosis: Clinical features and the curative role of liver transplantation

Today's article under review is the second of three papers I will be reviewing that were presented at the eleventh annual International Symposium on Amyloidosis, which was held in Woods Hole, Massachusetts in November of 2006. The papers presented at this symposium can be found in the book XIth International Symposium on Amyloidosis, edited by Drs. Skinner, Berk, Connors and Seldin, all of the Amyloidosis Center at Boston University.

This paper gives us some statistics on twenty patients with fibrinogen amyloidosis who were evaluated in the UK over the course of 10 years. There are some interesting findings regarding additional organ involvement and how that impacts the actual transplant surgery, as well as some promising post-transplant assessments. (In other words, this one is worth a careful read.)

Title: Hereditary Fibrinogen A alpha-chain amyloidosis: Clinical features and the curative role of liver transplantation (1)

Authors: N. D. Heaton, J. O. Grady, M. Rela, P. Muiesan, J. A. Wendon, L. Sizer, J. Sedgwick, M. Thomas, F. Murgatroyd, C. J. Mathias, H. J. Goodman, D. Rowczenio, A. Bybee, G. Tennent, P. N. Hawkins, and A. J. Stangou (King's College Hospital, London, UK; National Hospital for Neurology and Neurosurgery, London, UK; Centre for Amyloidosis and Acute Phase Proteins, Royal Free and University College Medical School, London, UK)

BookXIth International Symposium on Amyloidosis (2007)

Abstract: None

I do not know if the first sentence of this article was true in 2006, but it is definitely not true (or is at least misleading) today. Here it is: "Hereditary fibrinogen A alpha-chain Glu526Val amyloidosis (AFib) is the most frequently diagnosed form of hereditary amyloid in the U. K." Although fibrinogen amyloidosis is much more common in the UK than it is in the US, everything I have seen, such as the UK Amyloidosis Patient Information Site, indicates that ATTR is the most common form of hereditary amyloidosis in the UK. However, since there are over 100 mutations known to cause ATTR amyloidosis, I suppose the rankings may be different if each mutation is considered separately. Anyway, the first paragraph of the article then states that end stage renal failure typically occurs in patients with fibrinogen amyloidosis within one to five years of presenting with proteinuria and hypertension. In patients who receive just a kidney transplant, amyloid almost always recurs in the transplanted kidney within 7 years.

The twenty patients in this paper were evaluated for combined liver and kidney transplants at King's College Hospital in the UK between 1996 and 2006. Their ages when they first presented with symptoms ranged from 36 to 69, and they were assessed between the ages of 57 and 69. The median time from diagnosis to end stage renal failure was 29 months.

Part of the assessment of these patients was SAP scintigraphy, which provides a visual indication of where amyloid deposits are in the body. SAP scintigraphy was very accurate in identifying amyloid deposits in the kidneys as well as other organs. One interesting finding was that SAP scintigraphy would show amyloid deposits in the spleen even though conventional methods of analyzing the spleen did not detect any issues. The paper states that splenic involvement is usually clinically significant in AFib patients due to increased erythropoetin requirements. (Translation: A need for something like Epogen or Procrit due to anemia.) In fact, rupture of the spleen is such a concern that they have altered their surgical technique during transplants in these patients to reduce the risk of rupturing the spleen, as well as increased the vaccination regimen of patients who are on the waiting list.

Another part of the initial evaluation of these patients was a thorough assessment of their peripheral and autonomic neurological function. As we learned from Dr. Gertz' opening presentation at the familial amyloidosis meeting in October, the peripheral nervous system gives us feeling in our extremities and allows us to control the muscles in those extremities, whereas the autonomic nervous system is mostly out of our control and affects things like perspiration, heart rate, and the digestive system. The article states that about half of these transplant candidates showed some level of autonomic neuropathy affecting either the heart or the gastrointestinal tract. But the good news is that the autonomic neuropathy was resolved in the patients who received a liver and kidney transplant.

The article then gives some details on the outcomes of the transplants. Of the twenty patients evaluated, seven underwent combined liver and kidney transplant (LKT). Three of those patients either had not started dialysis or had been on dialysis less than six months at the time of transplant. The other four patients had been on hemodialysis at least two years at the time of transplant. The only complications during surgery were two cases where the spleen ruptured during surgery.

The patients who had not been on long term dialysis had fewer complications after their transplants than the ones who had been on dialysis at least two years. At the time this paper was written, six of the seven patients were still alive and their transplanted organs were functioning in the normal range. The authors of the paper did confirm there was no variant (mutant) fibrinogen circulating in the blood of these patients after their transplants. (More on that subject in a 2007 article.) Using SAP scintigraphy they could also determine that no new amyloid deposits appeared in the transplant patients, and the existing deposits regressed quite rapidly.

The conclusion of the paper states that the outcomes of combined liver and kidney transplants endorse it as a curative treatment for fibrinogen amyloidosis.


Before this paper was published there were a few isolated cases reported of combined liver and kidney transplant being used to treat fibrinogen amyloidosis, so now we have one paper reporting the outcomes of seven cases. All indications are that a combined liver and kidney transplant is curative, since a) the liver is the source of the variant fibrinogen, and b) the body appears to be able to eliminate the fibrinogen amyloid deposits once the source is removed and they stop accumulating. That differentiates AFib from ATTR (transthyretin amyloidosis) in two important ways. First, the liver is not the sole source of variant transthyretin, so patients with ATTR who undergo a liver transplant are still producing variant ATTR but at a slower rate. The second difference is that once amyloid deposits due to variant ATTR are formed, the wild-type (normal) transthyretin will continue to accumulate and build up those deposits. That makes ATTR much more difficult to manage, even after a liver transplant.

I was surprised by the reports of autonomic neuropathy in 50% of these transplant candidates. There was a case of peripheral neuropathy previously reported in a fibrinogen amyloidosis patient, but I do not recall any reports of autonomic neuropathy. It may be that this neuropathy is typically not clinically significant, so a thorough evaluation is not typically done and it is never discovered. In any case, it is good to know that it does improve after a liver transplant.

Before reading this paper I was aware that fibrinogen amyloidosis could eventually affect the spleen, and amyloid deposits are often found in the spleen on autopsy, but I had not really considered it to be clinically significant unless and until the spleen becomes enlarged or ruptures. However, this paper states that anemia is a sign of splenic involvement. Since Mom has anemia, and I know of some other AFib patients (AFibbers?) where anemia is or was an issue, perhaps it is reasonable to state that the spleen is involved once a person with fibrinogen amyloidosis becomes anemic. I don't know if that changes anything in terms of the treatment for the anemia, but it might be worth mentioning to your doctor if that is your situation. I would also recommend (not sure if I have mentioned this before) that anyone with fibrinogen amyloidosis who is on dialysis tell your doctor to be on the lookout for an enlarged spleen, and be aware of the signs of a ruptured spleen (severe pain in upper left abdomen), since that is an emergency medical condition that can be life threatening.

Speaking of spleens, I found the discussion of ruptured spleens in this paper interesting. They state that three of these patients had ruptured spleens, with two of those occurring during the transplant surgery. So if and when you are approved for a liver or liver-kidney transplant, that might be something worth mentioning to the transplant team before you get that phone call to rush to the hospital. You don't want to wait until you are about to be anesthetized to ask the surgeon, "Hey doc, are you going to use mesenteric bypass to avoid a sudden increase in splenic pulp pressure and splenic rupture?"

In summary, this paper definitely provides some more data pointing to a combined liver and kidney transplant being a cure for fibrinogen amyloidosis. I do not know if any of the other types of amyloidosis (hereditary or otherwise) can really be considered "cured" with any treatment. With AL amyloidosis, for instance, the doctors speak in terms of a patient's response to treatment (no response, partial response, very good partial response, and complete response), and even if a patient has a complete response there is no guarantee that the amyloidosis will not come back. So although an organ transplant is a major medical procedure with significant risk, at least it can be considered curative for fibrinogen amyloidosis based on the data in this paper from 2006. We will have to wait until 2009 and 2010 for some more published articles covering larger groups of patients. (But feel free to read ahead. You know where to find them.)

The next article review will give us some idea of how rare fibrinogen amyloidosis is compared to other types of familial amyloidosis.



(1) Skinner M, Berk JL, Connors LH, Seldin DC. XIth International Symposium on Amyloidosis: Taylor & Francis; 2010.

Monday, November 25, 2013

Article Review (2006) - Familial Amyloid Nephropathy of Fibrinogen A Alpha (E526V) Origin. Report of the First Case from Austria

Today's article review is the first of three papers I will be reviewing that were presented at the eleventh annual International Symposium on Amyloidosis, which was held in Woods Hole, Massachusetts in November of 2006. The papers presented at this symposium can be found in the book XIth International Symposium on Amyloidosis, edited by Drs. Skinner, Berk, Connors and Seldin, all of the Amyloidosis Center at Boston University. The book was published in July of 2007 and is currently available for only $219.95 at ($154.54 for Amazon Prime members.) If you would like to look at the book without spending that much money, Muriel Finkel will loan out her copy. (But try not to keep it for four months like I did.)

In our first paper from the 2006 Symposium, fibrinogen amyloidosis continues its global spread, this time into Austria.

Title: Familial Amyloid Nephropathy of Fibrinogen A Alpha (E526V) Origin. Report of the First Case from Austria (1)

Authors: S. Hargassner, G. Biesenbach, G. Syre, K. Altland, and R. P. Linke (General Hospital Linz, Austria; Institute of Human Genetics, Giessen, Germany; and Max-Planck-Institute of Biochemistry, Marinsried, Germany)

BookXIth International Symposium on Amyloidosis (2007)

Abstract: None

The patient in this article is a 63-year-old woman who initially presented with elevated serum creatinine. She was suspected of having lupus nephritis (kidney inflammation due to lupus) and was treated for that. Three months later she was admitted to the hospital with hypertension, serum creatinine of 3.18 mg/dl, proteinuria (3.5 grams per 24 hours), GFR of 16, and microhematuria (very small amount of blood in the urine). Her leading symptom was dyspnea (difficulty breathing), so she was initially treated for that, and then underwent further investigation.

A kidney biopsy was done, and Congo red staining showed significant amyloid deposits in the glomeruli. The biopsy was further analyzed immunohistochemically (staining against specific proteins), which showed the presence of fibrinogen. Genetic testing showed the patient had the Glu526Val mutation. She also had another fibrinogen mutation that, if I understand correctly, is a benign mutation that is randomly found in a small percentage of the population. She began hemodialysis a year later and was listed for a kidney transplant, although she was told a combined liver and kidney transplant might be curative.

There was no known history of kidney failure in her family. Both of her sons tested positive for the Glu526Val mutation, and her sister tested negative. The article then states that a de novo point mutation seems to be a possibility. (More on that later.)

The conclusion of the paper states some of the facts about fibrinogen amyloidosis that were known at the time, specifically:

  • Inheritance is autosomal dominant
  • Fibrinogen is produced in the liver
  • Family history is usually negative (for kidney issues)
  • Penetrance is incomplete
  • Most patients suffer renal failure alone
  • Combined liver and kidney transplantation appears to be curative

This paper describes another case where the patient presents with the classic symptoms of fibrinogen amyloidosis, which are hypertension, elevated serum creatinine and proteinuria. A kidney biopsy showed the characteristic sign of fibrinogen amyloidosis, which is amyloid deposits in the glomeruli. An additional symptom noted with this patient that I do not recall seeing before is microhematuria, which is a very small amount of blood in the urine (not enough to cause discoloration.) As Dr. Benson stated at the recent familial amyloidosis meeting in Chicago, over time you see a pattern of symptoms develop in patients and there is a typical progression of the disease, but occasionally there will be a patient who has not read the book and has something outside of the norm.

Regarding the possibility that this was a de novo mutation, I suppose that is always a theoretical possibility until genetic testing is done on both parents of a patient. But this case does fit the pattern of the propositus (first person diagnosed) being the first person in the family known to have any kidney issues, so I don't really know why the authors of this paper bothered to include the sentence about the possibility of this being a do novo mutation.

In the next article review from the 2006 symposium, we have our first paper that could be considered a study of a large number of fibrinogen amyloidosis patients (20), instead of patients from only one or two families.


(1) Skinner M, Berk JL, Connors LH, Seldin DC. XIth International Symposium on Amyloidosis: Taylor & Francis; 2010.

[Edited December 23, 2013. Minor change to first sentence.]

Wednesday, November 20, 2013

Pressure Relief

In our previous episode, Mom's nephrologist, Dr. N, had taken her off of one medication for heart palpitations and prescribed two additional blood pressure medications, bringing the number of blood pressure medications she is on up to five as of November 8. And in the ongoing quest to determine the cause of her high calcium, he scheduled her for a CT scan of her chest, abdomen and pelvic region on Tuesday, November 12.

Dr. N went over the results of the CT scan with Mom while she was at dialysis on Friday, November 15. He said there is an abnormality in her chest cavity, but it might be due to the talc pleurodesis surgery she had in July of last year. Dr. N called the surgeon, Dr. J, and Dr. J suggested that Mom have a biopsy done to determine if the abnormality is due to the surgery or something else. (I suppose it could be the talc material or the scar tissue.) Dr. N also wants to have x-rays taken of Mom's legs. Hooray, more tests and procedures . . .

Speaking of high calcium, the upper limit of the normal range is 10. So anything above that can be considered high. Here is a chart of her corrected calcium going back to February of this year:

Calcium Chart

(That chart may run off the edge of the page when viewed on the blog, but the next smaller size was too small to read easily.)

There is not really a clear trend in that chart, but her calcium was definitely above normal for four months starting in July of this year, and it was still at the upper end of the normal range with the most recent reading in November. Maybe the calcium level is just something that fluctuates with some dialysis patients, and Mom's calcium happens to be high or almost high anyway. If that is true, then there may not really be any underlying cause that needs to be addressed. We will see what happens over the next few months.

On November 15 Dr. N also increased the dosages on two of Mom's new blood pressure medications. That is probably a routine occurrence when starting a patient on a new blood pressure medication, to start at a low dosage and then increase it if necessary based on how the patient responds. Mom had a follow-up appointment with her internist, Dr. M, on Tuesday, November 19. Dr. M said Mom's blood pressure was headed in the right direction, and Mom is not yet taking the maximum recommended dosage of the blood pressure medication, so that's good. A few days before that appointment, however, Mom's pulse was around 150 bpm when she got up in the morning, and it stayed that way until late in the morning. Dr. N has taken her off the medication she had been taking quite awhile for heart palpitations, so hopefully that elevated pulse will not be a recurring issue. I know we will all rest a little easier once this blood pressure is under control.

Next up: Back to the article reviews.

Friday, November 15, 2013

High Pressure Calcium Scan

Before I begin today's update on Mom I want to discuss something that was recently mentioned in the online amyloidosis support group. It is an article titled "The Future of Amyloid Detection." Here is the link: It is about an imaging technique that has been developed to make amyloid deposits show up on a PET scan. I previously discussed a different amyloid imaging technique, SAP scintigraphy, in an article review posted on April 30 of this year. That method has been used by the UK National Amyloidosis Centre for many years, but as I understand it the substance the patient is injected with before the scan cannot be licensed for use in the US because it is derived from human blood. This latest method, developed at the University of Tennessee in the US, instead uses a synthetic peptide (known as P5), so it can be licensed for use assuming it is determined to be "safe." The article shows some comparisons of images using SAP scintigraphy vs. P5 PET scan in mice, and states that the two methods are equivalent for imaging the liver and the spleen, but P5 is better for imaging the heart and the pancreas.

I do not know how soon we can expect to see this scan in widespread use in the US, but there is a clinical trial for this peptide on the clinical web site that recently changed its status from "Recruiting" to "Closed." The title of the trial is "Radioimmunoimaging of AL Amyloidosis" and the responsible party is Dr. Alan Solomon of the University of Tennessee, another well-known doctor in the amyloidosis community. I assume the study is essentially complete and the results will be published in the near future. It is hard to predict what impact this new tool will have on the diagnosis and treatment of amyloidosis in the US, but I think any additional tools available to doctors can only be a good thing.

Ok, now to Mom. After a difficult trip home from Chicago on Sunday and a trip to the emergency room on Monday, she was feeling better for her appointment with her internist, Dr. M, on Tuesday, October 29. We decided my sister Amy would take Mom to this appointment so we would have two sets of ears there, and also so Amy could give Dr. M more details than Mom could about what happened the day before with the emergency room visit. The three main things discussed with Dr. M were:

  • The events since returning from Chicago. Dr. M said what happened can definitely be explained by the high blood pressure, the need for dialysis, and Mom not sleeping with her CPAP machine for three nights. Mom must sleep with her CPAP machine going forward, and we may have to be more cautious about letting her go three days without dialysis, such as from a Thursday to a Monday.
  • Blood pressure. We have been concerned about Mom's blood pressure creeping up and getting harder to control with medication. Dr. M said Mom's nephrologist should really be on top of that, since the kidneys play such a large part in regulating blood pressure. Mom already had a prescription for hydralazine which she was to take only as needed, when her systolic blood pressure (top number) was over 180. Since she is having to take that so frequently now anyway, Dr. M gave her a prescription to take it three times per day.
  • High calcium. Mom's nephrologist (Dr. N) is still trying to determine the cause of Mom's high calcium, but her internist (Dr. M) said Mom's September 16 blood tests did not show her calcium levels to be high. Well, that is confusing. Hopefully Mom can talk to Dr. N at the dialysis clinic on Friday.

The major concern now is the blood pressure, since after this latest addition Mom is now on three medications for her blood pressure. Earlier this year she was only taking one daily medicine for her blood pressure, with another one (clonidine) to take when her systolic pressure was over 160. Hopefully her nephrologist will get more involved and help bring her blood pressure down. She did feel well enough to drive down to Austin the following weekend and spend three nights. Yes, she did use her CPAP machine.

Mom usually sees the nephrologist at the dialysis clinic on Friday, but he was not there the first Friday after Mom's appointment with her internist so she did not see him until Friday, November 8 to discuss her blood pressure. In the meantime she had been keeping a close watch on it with the new medication prescribed by her internist, and it was better but still high at times. Dr. N agreed that they have to get her blood pressure down, so he made another change to her prescriptions. He took her off one medicine she was taking for heart palpitations, and he added two more for blood pressure. So now she is on five different blood pressure medications. (Geez, it was only three in the last paragraph.)

Dr. N did lower her dry weight, so that is some good news. Regarding the high calcium, he said he still wants to determine the cause although it was not very high. He did not know what the latest blood test results from the clinic showed, and Mom didn't either because the new dietitian has not been as consistent in providing those reports to the patients. (I do know it was 11.0 at her latest emergency room visit, which was after three days without dialysis.) The next test he wanted to have done is a CT scan (with contrast) of her chest, abdomen and pelvic region. She had that on Tuesday, November 12, but we will have to wait until the next blog post for those results.

Sunday, November 10, 2013

No sleep. No dialysis. No problem?

In our previous episode of As The Amyloid Turns, Mom and I had just arrived at DFW Airport on Sunday, October 27, after attending the 2013 Familial Support Meeting in Chicago. Mom was exhausted due to not having her CPAP machine for three nights, her blood pressure was high, her most recent dialysis was three days ago, and now she was throwing up. She said she felt a little better after throwing up, and she suspected it was the tuna sandwich she had for dinner at the Cincinnati airport. Since she and I split that sandwich and I felt fine, I had my doubts as to whether it was indeed food related. The shuttle van for the parking lot came to pick us up, and we made the trip to my truck without incident.

On the drive home Mom threw up just a little more (in a plastic bag, thank goodness.) She said she was not having any chest pains or shortness of breath, so I did not feel like it was an emergency room situation at that point. We got to her house and she still said she was not having any chest pains or shortness of breath, and we felt like she was just very tired and needed a good night of sleep with the CPAP machine. So she was going straight to bed, and I went on home, more than a little worried that she might not be able to drive herself to dialysis Monday morning.

My sister Laura called me Monday morning a little before 9:00 AM and said she had been unable to reach Mom on her cell phone. I knew Mom was going to try to get into dialysis early, so I called the dialysis clinic to see if she was there. They said she was not, which got me a little worried. I called her home number first and she answered. She said she had thrown up some more overnight and just did not feel like getting up and going to dialysis. So I started making phone calls to find out who could take Mom to dialysis and when could the clinic take her. In the meantime we found out that she had a mild fever, so the clinic recommended we take her to the emergency room given the fever and the nausea. My sister Laura took Mom to Plano Presbyterian hospital around 11:30 AM.

Laura called my home phone and spoke to my wife a little after noon and said Mom was really incoherent in the ER and her blood pressure was 236/114. So I left work (home) and headed to the hospital. When I got to Mom's room in the ER both my sisters were there, and I saw on the monitor that Mom's blood pressure was just a little over 200. Mom seemed tired but somewhat coherent, so things appeared to be under control. An ER doctor came in and said they were still waiting on the results of the blood tests, but Mom likely just needed dialysis. He said they would be giving her some clonidine intravenously to help bring the blood pressure down. Laura left shortly after the ER doc did, and I stayed a little longer. While I was there a nurse walked in, looked at me and Mom, and said, "Hey, I remember you guys." I recognized her, too. She was Mom's ER nurse on her June 3 visit to the ER, described in the June 18, 2013 blog post. I filled her in on what was going on and I stayed a little longer. Not much was happening in the ER, and Mom's blood pressure was slowly going down, so I went back home.

I had been home less than an hour when my sister Amy called and said the blood work showed Mom's potassium was high. The doctor suggested she have dialysis at the clinic today if possible, because she would have to be admitted in order to have dialysis at the hospital, and she probably would not have dialysis until the following morning (Tuesday). So I called the clinic to see if they could take her, and they said they could. My sister Amy could not take Mom to dialysis due to something she had to do, so I went back to the hospital and took Mom to dialysis after she was finally discharged. I could tell she was simply exhausted on the way there, and not altogether there, especially when I received a phone call from Laura on the way and Mom did not even ask me who called or anything about the phone call.

My sister Amy took Mom home after dialysis, and Laura and Amy were both there to help her eat a little food, take her evening medicine, and get to bed with her CPAP machine. They said she was really exhausted and incoherent. So for the second night in a row, Mom went to bed not doing too well. Hopefully getting a full night of sleep with the CPAP machine will get her a little closer to normal. Well . . .

She felt much better Tuesday morning after a good night's sleep. Maybe not as good as new, but definitely better than she felt on Monday. She happened to already have an appointment Tuesday with her internist for a routine checkup, and my sister Amy took her to that. We will cover that appointment in the next post.

Tuesday, November 5, 2013

2013 Familial Support Group Meeting - Day 2

This post will cover Day 2 of the 2013 Familial Support Group meeting, which was Sunday, October 27. After breakfast at the hotel Sunday morning we were shuttled back over to the meeting location. The agenda for today was a question and answer session all morning with the doctors, where people could submit their questions either in writing or by sending an email to Muriel. I had emailed a question to Muriel the night before asking about getting a tissue biopsy analyzed when you already know your mutation. The doctors always state that the only way to know a person truly has amyloidosis (of any type) is to confirm the presence of amyloid in a tissue biopsy. Congo Red staining will confirm the presence of amyloid deposits, but that alone does not tell the pathologist what type of amyloidosis the patient has. The specific protein making up the amyloid deposits is needed to make that determination, and there are additional stains or other methods that can be used for that. So in my question I set up the scenario where a patient knows what mutation he or she has due to genetic testing, and then they start to develop symptoms and get a biopsy. Then my question was: 

"If Congo Red staining shows biopsy is positive for amyloid, does that biopsy need to be analyzed further by one of the more advanced methods in order to type the amyloid, or is the Congo Red staining sufficient to confirm amyloidosis so this patient can pursue clinical trial and/or organ transplant options?”

Since this could be my scenario some day, I have wondered what would be the best thing to have done to my kidney biopsy if I ever have one. Should I insist that it be sent to the Mayo Clinic for a full analysis, or, since my mutation is known, is it sufficient to have it analyzed at whatever local pathology lab it would typically go to, as long as they know to do the Congo Red stain?

The meeting started, with Dr. Gertz of Mayo Clinic moderating the Q and A session. He would read the questions and assign them to whatever doctor or doctors he felt could answer it best. He did tend to group similar questions together and there were a lot of very good questions asked. The notes from today's session are also included in the PDF file available for download at the Amyloidosis Support Groups web site. On the familial page, look for "Familial Amyloidosis Conference Notes and Presetation" below the list of doctors for the 2013 meeting. Here is the direct link to the PDF file: The Q and A session begins on page 37 of the October 31, 2013 version of the file.

So at this point it was a matter of sitting back and listening to the questions and answers. The majority of the questions were not directly applicable to fibrinogen amyloidosis, but I found most of the discussion very informative and I had no trouble staying awake. Mom, on the other hand, did have a bit of trouble. Well, she had a lot of trouble staying awake. I had noticed after we got to the hotel Saturday night that she seemed a little tired although it was only about 7:00 PM. I realized she had not brought her CPAP machine on this trip, so two nights of sleeping without it was starting to catch up to her. She also checked her blood pressure and found it was high, so she took the pill that she is supposed to take as needed when her systolic pressure (top number) is over 180. Sunday morning at the hotel it was high again, and she got tired just rolling her suitcase down to the lobby. Now here we are at the meeting Sunday morning, and she simply cannot stay awake. I feel very confident in stating she was asleep more than she was awake. At least twice I suggested that she simply give up and lay her head down on the table.

As the scheduled end time for the meeting was approaching, I was starting to wonder if Dr. Gertz would ever get to my question. He finally did, but instead of setting up the scenario I presented, here is what he asked: "Is Congo Red staining sufficient to confirm amyloidosis so a patient can pursue clinical trial and/or organ transplant options?” That, of course, leaves out the most important part of my scenario, about the patient already knowing what mutation they have. He gave the question to Dr. Angela Dispenzieri of Mayo Clinic, and she began by saying something about it depends on whether or not the patient is a known carrier. She did quickly say that typing the biopsy was not all that critical in that case, and then she spent the rest of her time talking about other techniques for analyzing biopsies. So I did get my question answered, and the last page of the PDF file with notes from the meeting also has my question and says that typing the amyloid in a tissue biopsy is not necessary if the mutation in the patient's family is already known. I have made some minor changes to the "What should I do now?" page as a result.

Here are some of my random thoughts about the meeting and a few things I learned, in no particular order:
  • This a great group of doctors that come together for these meetings. They can explain things very well, they have a lot of respect for each other even though they disagree at times, and they are not afraid to admit when they do not know something.
  • I learned some things about transthyretin mutations (ATTR amyloidosis) that I was unaware of before the meeting. I had heard the term "wild type TTR" for some time and eventually learned that "wild type" really means "normal" in that context (as opposed to mutated), but what I did not know was that even after a liver transplant, the existing amyloid deposits can serve as a base for the normal TTR to continue to build on. That is why a liver transplant is far from being a cure for patients with ATTR. Patients who have received liver transplants for ATTR are a little frustrated at their inability to participate in clinical trials, and understandably so since their symptoms do tend to progress.
  • Like at the last meeting, attending this meeting does make me think that we fibrinogen patients are somewhat fortunate not to have an ATTR mutation, given the peripheral neuropathy, gastro-intestinal, and cardiac issues often associated with those. Generally speaking, it seems like the ATTR mutations have more impact on a person's quality of life (not that dialysis is a cake walk, either.)
  • Although the majority of the meeting is geared toward those with ATTR mutations, I still think it is worthwhile for patients with one of the rarer mutations like fibrinogen to attend for a couple of reasons. First, just like at the local support group meetings, there is some benefit to meeting others with any type of amyloidosis and sharing stories of diagnosis, impact on quality of life, impact on the family, etc. Second, this is likely the only opportunity to meet others outside of your family with the same mutation. At the 2009 meeting I believe Cathy T. was the only fibrinogen patient in attendance. At the 2011 meeting there were two families represented, and at this year's meeting there were four families represented. I do intend to give Muriel some ideas on how to make the meeting more beneficial to those with non-TTR mutations, with the understanding that it will be difficult to clone Dr. Benson.

The meeting wrapped up after lunch, and we said our goodbyes and waited for the van to take us to the airport. Mom got wheelchair assistance at the airport, which was an absolute necessity given how far we would have had to walk otherwise. It was nice to get ahead of the long security line, too. We caught a connecting flight in Cincinnati and had dinner there.

Mom was very tired during most of the flight from Cincinnati to DFW. Initially she was cold, but near the end she got up to use the restroom and I could tell when she came back to the seat that she wasn't doing well and seemed to be getting warm. We landed at DFW a little after 9:00 PM, and Mom had wheelchair assistance as far as baggage claim, which again was definitely necessary given the distance from the gate. They were having some sort of technical difficulty getting that baggage claim carousel started, and I jokingly told Mom I hoped the problem was not due to my bag getting stuck and chewed up somewhere along the way. Some of you may remember my baggage claim experience after the Familial Meeting in 2011, when my suitcase came out looking like this:

David's suitcase after 2011 Familial Meeting

After the carousel started I anxiously waited for our bags to come out, and they finally appeared, undamaged. Now we needed to get downstairs to catch the shuttle to where my car was parked off-airport. There was no good way I would be able to push Mom and pull all of our luggage at the same time, but it was a relatively short walk to the elevator to go down so I figured Mom could make it. We got downstairs, walked outside, and then before I could call the parking lot to ask them to come pick us up in the shuttle van, Mom started throwing up.

This post seems long enough, and it has been a few months since we had a good cliffhanger episode, so our story will continue with the next post.

Sunday, November 3, 2013

2013 Familial Support Group Meeting - Day 1

Today's post will cover Day 1 of the 2013 Familial Support Group meeting, which was Saturday, October 26. The monthly blog stats are at the end, and once again you may need an atlas to find all five of the new countries that visited the blog for the first time last month.

The 2009 and 2011 Familial Support Group meetings were held at Muriel Finkel's place of business, Finkel Supply, in Itasca, IL. We were really a little too big for that location at the 2011 meeting, so Muriel decided to have it at a different location this year. She chose Salt Creek Golf Club in Wood Dale, IL. After breakfast at the hotel they started shuttling attendees over to the meeting location, where we were greeted with a nice welcome sign:

Welcome Sign

After picking up our name tags and a hot-off-the-presses copy of the very well done Amyloidosis Awareness brochure, we sat in the large meeting room. The projected attendance for the meeting was around 230 patients and caregivers, although I recently read a comment indicating the actual attendance was closer to 210. In any case, we were still packed in there tightly. The golf club literature says they can accommodate groups of 200, so you might say we were slightly over capacity, especially when you add about 15 doctors and pharmaceutical reps to the group.

Speaking of doctors, these doctors are the rock stars of the amyloidosis medical community. They are the ones who lead the way doing the research and publishing the articles on amyloidosis. They see more amyloidosis patients in a week than most doctors see during their entire career. It is quite amazing that they are willing to give up a weekend and gather in Chicago for this meeting. I am not going to go into much detail on most of the presentations because those are gradually being uploaded (as Muriel gets permission) to the familial page of the Amyloidosis Support Groups web site at this link: There is also a link to a large PDF file with notes that were taken for each presentation and for the Q and A session on the second day. Look for "Familial Amyloidosis Conference Notes and Presentation" under the list of doctors at the 2013 meeting.

After Muriel said a few words the meeting started with Dr. Morie Gertz, Chair of Internal Medicine at the Mayo Clinic in Rochester. He talked mainly about the nervous system and the heart, and how ATTR amyloidosis them both. N
ext up was Dr. Martha Skinner of Boston University. She was director of the Boston Amyloidosis Center for 19 years, and is now officially retired as Professor Emerita. Dr. Skinner was the one who explained to us that Mom had some type of familial amyloidosis after her Boston evaluation in June of 2010, so we consider Dr. Skinner to be the doctor who diagnosed Mom. She talked about the history of familial amyloidosis and gave an overview of the various types and the percentages of each. About 15% of all amyloidosis cases are familial, with ATTR (transthyretin mutations) accounting for 10 to 12%. The five remaining types each make up less than 1% each of the total amyloidosis cases. Those five are fibrinogen, apolipoprotein A1, apolipoprotein A2, lysozyme, and gelsolin.

The next speaker was Teresa Kruiselbrink, a genetic counselor from Mayo Clinic in Rochester. She had a very good presentation about the issues with genetic testing, the benefits and limitations, and the questions an individual should ask themselves when deciding whether or not to get tested. I won't go into any more details on her presentation since I can talk for a long time about genetic testing. The conference notes have a very good summary of her talk, and I may use that as a starting point for a future blog post.

Then we took a break, and Cathy T. asked me if I had located the new person with fibrinogen amyloidosis from Arkansas, because Cathy had been looking for her as well. So we both wandered around looking at name tags during the break, but we were unsuccessful.

After the break, Dr. Annabel Wang of UC Irvine and Dr. Janice Weisman of Boston University discussed peripheral neuropathy, specifically, what is it and how does a doctor do a proper exam for it. It was during this presentation that things got interesting for me. Yes, the presentation was interesting (although fibrinogen amyloidosis rarely causes peripheral neuropathy), but what was really interesting was when my phone started vibrating. I put it on vibrate before the meeting started, and unfortunately I do not always feel it when it vibrates depending on where it is in my pocket. It turns out I had missed a phone call earlier and there were four text messages and one voicemail waiting for me. Two text messages were from my wife telling me about some good things our son was doing that day, and the other two (actually one long one divided in two) were from someone I'll refer to as SS who said she was at the meeting with her mother and daughter, all three of them had been diagnosed with fibrinogen amyloidosis, and they would like to meet me. She told me where they were sitting in the room, so I wrote her back and told her where we were sitting and that we would come over to their table at the lunch break. I did not recognize her name as the person from Arkansas, so I was quite anxious to meet this family and find out their story.

The next presentation was by Dr. Martha Grogan, a cardiologist at Mayo Clinic Rochester. I had met her previously at an amyloidosis support group meeting in Dallas in November of 2011. (Good grief it's hard to believe that was two years ago.) Her presentation was really excellent, in part due the very well done graphics and animations in the Powerpoint slides. The main takeaways from her presentation are that cardiac amyloidosis is very easily misdiagnosed because the symptoms are so similar to other more common heart ailments, and there is no particular test that can be used to test for cardiac amyloidosis. It takes more of an overall assessment, beginning with an echocardiogram. (Note: Cardiac involvement is rare with fibrinogen amyloidosis, but once you have confirmed amyloidosis in the kidneys it is important to be aware of the possibility and get some baseline measurements before problems appear.)

Then it was time to break for lunch and we finally got to meet SS, who had sent me the text message. It turns out that her mother is the one from Arkansas I was aware of before the meeting and had sent an email to. Her mother's kidneys are functioning at about 17%, so she is not on dialysis yet. SS and her daughter both have the mutation but are currently asymptomatic. So that was interesting to have three generations in one family who all have the fibrinogen mutation. We talked some during the breaks that day, but I wish we had more of an opportunity to talk.

The first presentation after lunch was from Dr. Steve Zeldenrust of Mayo Clinic Rochester. He talked primarily about TTR mutations and the use of organ transplants in their treatment. Next up was Dr. Merrill Benson of Indiana University. Dr. Benson is probably the world's foremost expert on all types of familial amyloidosis, having had a part in discovering around half of the mutations, maybe more. He discussed the non-TTR mutations, the organs affected by each one, and the use of organ transplants in their treatment. Regarding fibrinogen amyloidosis, he said that a liver transplant appears to be curative, and he would recommend getting a liver transplant before the serum creatinine levels go over 2.1. As he put it, original equipment tends to work better. If you get just a liver transplant and down the road you need a kidney, then get a kidney at that time. (Early detection is obviously important here. I'll have more to say about this subject a few posts down the road.)

Next up was Dr. Maria Picken of Loyola University. She discussed amyloidosis from the pathologist's perspective. She gave the history of Congo Red stain, which was initially used as a dye in the textile industry, and then she talked about different types of biopsies (fat pad vs. tissue from an organ). Unless I missed it, I don't think she discussed the more advanced analysis techniques like immunohistochemistry or laser microdissection. (Not to worry, I'll be reviewing some articles on that later on.)

During the afternoon break I met the husband of a fibrinogen amyloidosis patient from Washington I had swapped a few emails with in the past. I had no idea he was coming to the meeting, so that was another neat surprise. I was able to learn more about his wife's journey with amyloidosis, and it turns out she was also diagnosed after a Boston evaluation in 2010.

After the break the presentations on clinical trials began. Since all of the drug development is geared toward ATTR, the only clinical trial (in the US) applicable to fibrinogen amyloidosis is the doxycycline trial, which I wrote about back in January. Dr. John Berk from Boston was on the agenda to talk about the Diflunisal and doxycycline trials, but unfortunately the bulk of his presentation was about Diflunisal. He did talk about doxycycline toward the end of his presentation, and the main points he mentioned about it were:

1. The trial is open to patients with any type of amyloidosis as long as there is something measurable. (For fibrinogen amyloidosis that would be things like creatinine, GFR, and proteinuria.)
2. Study participants will take doxycycline twice per day for one year.

The next three presentations were about other trials for the various drugs that have been developed to treat ATTR. They weren't really applicable to us Afib patients but I still found parts of them interesting since I'm so nerdy anyway.

The last thing on the agenda for the day was a series of concurrent workshops, where there were eight areas set up where doctors were leading discussions on eight different topics and attendees were free to roam from topic to topic. I hung out at the clinical trials session the whole time, since I wanted to ask Dr. Berk some more questions about the doxycycline trial. Since all eight sessions took place in the same large room, and there were many pockets of people carrying on their own conversations, it was very hard to hear, at least in the session where I was.

I eventually was able to ask Dr. Berk two questions. First I asked if there are any fibrinogen amyloidosis patients on the doxycycline trial. He said he did not know because he had not reviewed the data. (The entry for this trial indicates that it started recruiting in August of 2012, and they expect to complete gathering data in December of 2014.) My second question was whether or not there was any reason to suspect that doxycycline would be particularly effective against fibrinogen amyloidosis, since the amyloid deposits are primarily in the glomeruli of the kidneys. (I was curious about this because doxycyline has been shown to be effective at breaking down amyloid deposits in vitro, which means outside the body like in a petri dish or a test tube. Since the glomeruli are essentially in the bloodstream, doxycycline that is circulating in the bloodstream would have direct access to the amyloid deposits in the glomeruli, and hopefully break them down rather quickly.) Dr. Berk thought about it for a bit and said it was an interesting hypothesis, but they have no data to say one way or another at this point. So I got the impression that he understood my line of reasoning behind the question, and the fact that he did not quickly say "no" gives me a little hope that I might be onto something. I suppose we will just have to wait for the trial results to be published to see if there are any fibrinogen patients enrolled. This brings up another reason why genetic testing and early detection are so important, because it means more people are available to participate in clinical trials.

After the concurrent workshops concluded we had dinner at the golf club and then we were shuttled back to the hotel. Next up is the Q and A session on day 2, and then the wrap-up and trip back home.

=====Monthly Blog Status Update=====

Total posts: 106 (5 in October)

Total pageviews: 8600 (~1000 in October)

Email subscribers: 6

Total number of countries that have viewed the blog: 79

5 new countries viewed the blog in October:
Burkina Faso