Tuesday, October 29, 2013

Getting to the 2013 Familial Support Group Meeting

Today's post will get us up to the Familial Amyloidosis Support Group meeting Mom and I attended in Chicago this past weekend. The next post will be the full meeting report, or maybe just the first day. We'll see.

Mom and I attended the previous familial amyloidosis meeting in October of 2011, and there was never any doubt we would try to attend the next one. Two short years later, and here we are. Since the meeting takes place on Saturday and Sunday, we planned on doing what we did the last time, which was to arrive on Thursday and take a train into Chicago on Friday and do touristy stuff. Since Mom is on dialysis now we had to work that into our plans, so we scheduled dialysis in Chicago for Thursday, October 24. We had to make our flight reservations long before the dialysis could be scheduled, so we scheduled a very early flight to give us the most flexibility. That meant waking up at 3:00 AM Thursday morning so we could catch a 6:00 AM flight. <yawn>

So on the flight to Chicago the flight attendants came by with the drink cart, and I got orange juice and Mom got coffee. I drank my orange juice rather quickly so I could go back to sleep, and the next thing I recall was being awakened by something on my right leg. At first all I could feel was wetness. I opened my eyes to see Mom's coffee cup on its side, coffee all over her lap tray, and Mom soaking up what she could with her tiny napkin. The next thing I felt was heat. The heat of hot coffee soaking through my blue jeans. Did I mention it was hot coffee? Did I mention it was too hot for Mom to drink, which is why she fell asleep holding the cup? I would pull one part of my pants away from my skin only to feel heat on another part. Eventually I realized there was nothing I could do other than wait for the heat to die down, which probably seemed to take longer than it actually did. Mom also got coffee on her seat and pants as well. Once my leg was no longer on fire I was able to determine that the top of my pants leg was wet from a little below my pocket to just above my knee. But what was worse than that, and made it hard to get back to sleep, was the smell of coffee. We were able to laugh about it, and I told Mom that spilling coffee on me was better than spilling it on a stranger. Later on I realized how lucky I was not to be wearing short pants instead of blue jeans. (For those of you who are concerned, my leg was not blistered or scarred by the coffee incident.)

The remainder of the flight to Chicago was uneventful, and we landed, picked up our baggage, and called the phone number we had been given to request pickup at the airport. Muriel Finkel answered the phone and I told her where we were. She said her husband Steve would be right there in a white car with a license plate that said "AMYLOID." We waited outside with our slightly damp pants in the 38 degree Chicago air for Steve to arrive, and sure enough, that is their license plate:


The Amyloid Express

Steve took us to the hotel, and we just waited in the lobby for awhile since our rooms weren't ready yet and Mom didn't need to be at the dialysis clinic until 3:30 PM. We took the hotel shuttle to a nearby restaurant for lunch, and then after checking into our rooms we took the shuttle to the dialysis clinic. Mom was told to be there at 3:30 PM for her 4:00 PM session, but she did not actually start dialysis until close to 5:00 PM, which meant she would not be done until about 9:00 PM. Thank goodness I brought a book and my computer, and they have free wifi at the clinic. Mom called me soon after she started and said they had to give her some clonidine because her blood pressure was so high. That seems to be happening more frequently now, which is not good. We took the shuttle back to the hotel after dialysis and had some food delivered to the room for a late dinner.

Friday morning we took a train to Union Station in Chicago and then a cab to Millennium Park. The most interesting thing at Millennium Park is the stainless steel sculpture "Cloud Gate," nicknamed "The Bean" due to its shape.

Cloud Gate

Cloud Gate

If you look closely you can see me and Mom in the reflection in that picture. We are just under the trees, a little to the right of the sun. If you cannot find us there, maybe you can in the next picture. This one was taken from underneath the sculpture, and I know our reflection appears at least five times. Here's a clue: I'm wearing a blue toboggan hat.

Underneath Cloud Gate

Oh, how I would love to sit under that sculpture at night with a laser pointer . . .

After Millennium Park we had the mandatory Chicago-style deep dish pizza for lunch, and then we went on an architectural river cruise. It was very informative and I learned a lot about architecture and Chicago. Two interesting facts that really stuck in my mind are:

1. Michigan Avenue used to be the shore of Lake Michigan. All or most of the land currently east of Michigan Avenue, up to half a mile in some places, is man-made.

2. The Chicago River used to flow into Lake Michigan. Around 1900 a canal was dug so it would flow the other way. Now water flows from Lake Michigan into the Chicago River, which flows into the Des Plaines River, which flows into the Illinois River, which flows into the Mississippi River, which flows into the Gulf of Mexico.

I had planned this trip into Chicago to minimize the walking for Mom, and she did very well, including the stairs we had to take to get to and from the river cruise. After the river cruise we took a cab back to Union Station so we could take the train back to the station near the hotel. We freshened up a bit and then went downstairs for the meet and greet and eat, where the meeting attendees gather the night before the first day of the meeting.

The first couple we met was from Portland, Oregon. He was diagnosed with an ATTR mutation in March and was dealing with polyneuropathy. His mother and grandmother likely had the same mutation based on their symptoms before they died, but they were not diagnosed with amyloidosis. We talked with Cathy T., the fibrinogen amyloidosis patient who received a liver transplant in 2010, and her husband Lon. They are doing well and showed us a picture of 18 of their 19 grandchildren. (I'm going from memory there, so those numbers may be off by one or two.) I met up with SA, the woman I met at the Dallas Support Group meeting in June of 2012, and her father. One person I looked for but did not meet was a fibrinogen amyloidosis patient (female) from Arkansas I recently became aware of as a result of an email Muriel had forwarded to me. I asked Muriel if she was there but Muriel did not know because she had never met her either.

It would be a glaring oversight if I did not mention the very excellent dessert one of Muriel's employees made for the Friday night gathering. Oreo Balls. Oh my goodness. Google it. Make it. Eat it. Trust me.

Next up: Day 1 of the meeting

Thursday, October 24, 2013

Article Review (2006) - Hereditary fibrinogen A alpha-chain amyloidosis

If everything went according to plan, this post was automatically sent shortly after Mom and I arrived in the Chicago area to attend the familial amyloidosis meeting. If I have time I will post one or more updates this weekend. Otherwise I will certainly post my synopsis of the meeting next week.

Today's article under review is not actually an article, but it was in the correspondence section of a medical journal. 

Title:  Hereditary fibrinogen A alpha-chain amyloidosis (1)

Authors:  Stephen W. Lane, Hugh J. Goodman, Leo Francis, Andrew Bofinger, Peter N. Mollee (Princess Alexandra Hospital, University of Queensland; Royal Brisbane and Women's Hospital Brisbane, Queensland, Australia; National Amyloidosis Centre, London, UK)

Journal:  Pathology - The Journal of the Royal College of Pathologists of Australasia (2006)

Abstract:  None

Here is a link to the article (not free) if you would like to follow along: http://journals.lww.com/pathologyrcpa/Citation/2006/38040/Hereditary_fibrinogen_A_alpha_chain_amyloidosis.24.aspx

This article describes what the authors believe is the first case of a patient being diagnosed with fibrinogen amyloidosis in Australia. A 62-year-old man presented in 2004 with sacral oedema, hypertension and proteinuria. Eventually a kidney biopsy was done which showed deposits in the glomeruli that stained positive with Congo red. Various tests were done to determine if he had primary amyloidosis, but when those all came back negative his doctors asked for assistance from the National Amyloidosis Centre in the United Kingdom. They confirmed the amyloid deposits in the glomeruli, and some additional analysis of the biopsy material showed slightly stronger staining for fibrinogen. Genetic testing showed the Glu526Val mutation in this patient.

The article then gives a short description of the various types of amyloidosis, followed by a paragraph about fibrinogen amyloidosis and how it compares to some of the other hereditary types. Fibrinogen amyloidosis is somewhat unique due to the fact the kidneys are typically the only organ affected, especially in the early stages of the disease. For instance, amyloidosis caused by transthyretin mutations (ATTR) typically does not involve the kidneys, and amyloidosis caused by apolipoprotein A-I or lysozyme mutations may involve the kidneys but usually something else is clinically significant.

The article then discusses some of the challenges involved in determining the amyloid type from tissue biopsies, and includes this statement about fibrinogen in particular: "In AFib amyloidosis, the staining of deposits with antifibrinogen antibody is usually positive but with varying intensity and is dependent on specimen preparation and the specific mutation involved."

After providing some general guidelines on how to diagnose AL amyloidosis vs. a familial type, there is a paragraph about treatment for fibrinogen amyloidosis. They mention kidney transplants, with the caveat that renal failure often occurs within 5 to 7 years as a result of amyloid deposition in the transplanted kidney. The article mentions combined liver-kidney transplants but considers that an experimental therapy at this point, since there is no direct evidence of a survival advantage over just a kidney transplant.


In this article we have another patient who presents with the typical symptoms of fibrinogen amyloidosis, and then a kidney biopsy shows amyloid deposits in the glomeruli. Compared to some patients in previous articles, this patient was very fortunate to be properly diagnosed due to some good work by his doctors. First, it was good work to diagnose him with any type of amyloidosis in the first place. Then they did the right thing by not treating him with chemotherapy for AL amyloidosis, since that does more harm than good. Unfortunately he would not have been the first patient with a familial type of amyloidosis to receive chemotherapy because the doctors thought he had AL amyloidosis.

One topic the article mentions that I don't think I have discussed before is whether or not fibrinogen amyloidosis can be determined from a kidney biopsy. As the article mentions, there are specific stains which will illuminate fibrinogen, but the intensity varies and it is dependent on preparation of the specimen. There are some future articles that discuss this in much greater detail, including the newer techniques that go beyond simply staining.

Next up will hopefully be a report from the Windy City.


(1) Lane SW, Goodman HJ, Francis L, Bofinger A, Mollee PN. Hereditary fibrinogen A alpha‐chain amyloidosis. Pathology - Journal of the RCPA. 2006;38(4):380-382 310.1080/00313020600820823.

Friday, October 18, 2013

Article Review (2006) - Successful Hepatorenal Transplantation in Hereditary Amyloidosis Caused by a Frame-Shift Mutation in Fibrinogen A alpha-chain Gene

The article under review in this post is sort of a follow-up to an article that was published earlier, since it follows the progress of the same two patients. The original article, published in 1997, was Renal Amyloidosis With a Frame Shift Mutation in a Fibrinogen A Alpha Chain Gene Producing a Novel Amyloid Protein (1), and I reviewed that article on April 18, 2013. That article described a father and son who were found to have a new mutation causing fibrinogen amyloidosis. This mutation not only seemed to have an earlier age of onset than the Glu526Val mutation but it also caused amyloidosis to quickly recur in kidney transplants of both patients. So what do you do after a kidney transplant fails? Let's find out . . .

Title: Successful Hepatorenal Transplantation in Hereditary Amyloidosis Caused by a Frame-Shift Mutation in Fibrinogen A alpha-Chain Gene (2)

Authors: C. Mousson, B. Heyd, E. Justrabo, J.-M. Rebibou, Y. Tanter, J.-P. Miguet and G. Rifle (University Hospital, Dijon, France; University Hospital, Besancon, France)

Journal: American Journal of Transplantation (2006)

Hereditary systemic amyloidosis comprises several autosomal dominant diseases caused by mutations in a number of plasma proteins, including the fibrinogen A alpha-chain. Four mutations in the fibrinogen A alpha-chain that are able to induce amyloidosis have been identified so far, the most common being the Glu526Val mutation. We have observed a family in which the father and his son reached end-stage renal failure because of renal amyloidosis induced by a frame-shift mutation in the fibrinogen A alpha-chain gene producing a novel amyloid protein. Two kidney transplantations in the father and one in the son resulted in fast graft loss caused by recurrence of amyloid deposition. We then performed hepatorenal transplantation in the son. Three years later, liver and kidney functions are normal without recurrence of amyloid deposition. This case, together with three others with the Glu526Val mutation in the extensive literature, suggests that liver transplantation can cure hereditary fibrinogen amyloidosis, whatever the mutation may be.

Here is a link to the article if you would like to follow along:


The first patient described is the father, who developed kidney issues in 1984 at the age of 31. A kidney biopsy showed amyloid deposits in the glomeruli, but liver, bone marrow and rectal biopsies were all negative for amyloids. He was believed to have AL amyloidosis so he was treated with chemotherapy, which offered no improvement so his kidney function continued to decline to the point where he needed hemodialysis. He received a kidney transplant in 1988 at the age of 35. A biopsy two years later showed the presence of amyloid in the transplanted kidney, and he started hemodialysis again in 1994. The transplanted kidney was removed in 1995 and he received another kidney transplant in 1996. That kidney was also quickly affected by amyloid deposits and he was back on hemodialysis in 2001.

Analysis of the first transplanted kidney after it was removed showed that he had a frame-shift mutation in the fibrinogen A alpha-chain gene, as described in the 1997 article.

The son of this patient developed kidney issues in 1992 at the age of 12. A kidney biopsy showed amyloid deposits in the glomeruli, and he started peritoneal dialysis in 1993. DNA analysis showed he had the same fibrinogen mutation as his father. He received a kidney transplant in 1995 at the age of 15. He developed proteinuria and hypertension one year later, and a kidney biopsy showed amyloid deposits in the transplanted kidney. He started peritoneal dialysis again in February of 1998, then went on hemodialysis in 2000.

So at this point there were three failed kidney transplants, two in the father and one in the son. It was obvious that this particular form of fibrinogen amyloidosis would affect a transplanted kidney very quickly, so it was unreasonable to have the son undergo another kidney transplant. Since they knew fibrinogen was produced in the liver, and liver transplants had been used to treat other forms of familial amyloidosis, they decided to do a liver and kidney transplant on the son. That transplant occurred in May of 2002, and his kidney and liver functions rapidly recovered. Three years later, when this article was written, he was doing well with perfectly normal kidney and liver function. The father was waiting on a combined liver and kidney transplant at the time this article was written.

The article then discusses the use of liver transplants to treat other forms of hereditary amyloidosis, primarily those due to transthyretin mutations. Although the progression of the disease is slowed, liver transplants do not appear to be a "cure" for other types of amyloidosis because transthyretin, for instance, is produced in a few areas of the body in addition to the liver. "On the other hand, fibrinogen is only synthesized by the liver. Therefore, it can be postulated that liver replacement can really cure mutant fibrinogen-induced amyloidosis." The article then briefly describes the three cases of combined liver-kidney transplants for fibrinogen amyloidosis that have been previously published. Those results indicate that a liver transplant can cure fibrinogen amyloidosis.

The article closes with a discussion of domino liver transplants, where a cadaver liver is transplanted into patient A, and patient A's liver is transplanted into patient B. Domino liver transplants have been done with familial amyloidosis patients, since their liver function is typically fine and a person with liver failure would gladly take that liver since it would usually take many years for any amyloidosis symptoms to become evident. In the case of this particular patient, however, since they knew this mutation caused rapid failure of a transplanted kidney, they did not consider using his liver in another patient.


Although this article is about a fibrinogen amyloisosis mutation other than Glu526Val, it does add to the general discussion about a liver transplant being curative for fibrinogen amyloidosis. Upcoming articles will have more reports of transplants in the treatment of fibrinogen amyloidosis, and there will be more reports of patients in other countries being diagnosed with it. The number of articles per year definitely increased in 2006, so it will take awhile to catch up to the current day with article reviews.

Next up, we hear from the land down under.


(1) Hamidi Asl L., Liepnieks J.J., Uemichi T., Rebibou J.M., Justrabo E., Droz D., Mousson C., Chalopin J.M., Benson M.D., Delpech M., Grateau G. Renal amyloidosis with a frame shift mutation in fibrinogen a α-chain gene producing a novel amyloid protein. Blood. 1997;90:4799–4805.

(2) Mousson C, Heyd B, Justrabo E, et al. Successful hepatorenal transplantation in hereditary amyloidosis caused by a frame-shift mutation in fibrinogen A alpha-chain gene. Am J Transplant 2006; 6: 632-635.

Saturday, October 12, 2013

Article Review (2003) - Orthotopic liver transplantation for hereditary fibrinogen amyloidosis

Today's article under review is another article that was previously reviewed but only recently acquired. It is from 2003 and I first reviewed it on May 18, 2013. There is not a lot to add to the previous review since it is a relatively short article anyway, so I think I will just start with a copy of the previous review and modify that as necessary.

Title: Orthotopic liver transplantation for hereditary fibrinogen amyloidosis (1)

Authors: Zeldenrust, S.; Gertz, M.; Uemichi, T.; Björnsson, J.; Wiesner, R.; Schwab, T.; Benson, M. (Mayo Graduate School of Medicine, Rochester, MN; Indiana University School of Medicine, Indianapolis, IN)

Journal: Transplantation (2003)


Systemic amyloidosis results from the deposition of insoluble protein fibrils in various organs and tissues. To date, several different proteins have been associated with amyloid fibril formation, including immunoglobulin light chain, serum amyloid A protein, and transthyretin. Recent reports have shown that variant fibrinogen chains can form amyloid in certain kindreds. Hepatic transplantation has previously been reported in the treatment of hereditary amyloidosis associated with variant transthyretin proteins, which are mainly synthesized in the liver. This article reports the first use and long-term follow-up of combined hepatic and renal transplantation in the successful treatment of two patients with hereditary fibrinogen amyloidosis. Both patients experienced sustained improvement in renal function and nutritional status at 6 1/2 years and 28 months of follow-up, respectively. Orthotopic liver transplantation is effective and potentially curative treatment of hereditary fibrinogen amyloidosis.

I want to explain the first word in the title of this article so you don't have to look it up. "Orthotopic" simply means something is occurring in the normal place in the body. In the case of organ transplants, a liver transplant is typically orthotopic because the old liver is removed and the new one is put in its place. Kidney transplants are typically not orthotopic because the old kidneys are left in place and the new kidney is placed below them.

The article begins with a brief overview of systemic amyloidosis and some of the hereditary types that were known at the time. Then while discussing fibrinogen amyloidosis the article has this sentence: "Synthesis of fibrinogen is exclusively hepatic, making liver transplant theoretically curative in hereditary fibrinogen amyloidosis." So the authors are suggesting that since the liver is the sole source of fibrinogen, a liver transplant could be considered a cure. That will be a recurring topic of discussion as we review articles published after this one.

Case 1 in this article was a 62-year-old male who presented with high blood pressure in his thirties. He is a member of an Irish-American kindred with the Glu526Val mutation. His serum creatinine was 2.7 mg/dL and he had proteinuria. A kidney biopsy showed extensive amyloid deposits in the glomeruli. His renal failure progressed and his serum creatinine rose to 4.5 mg/dL. It was known that both his father and brother had been diagnosed with renal amyloidosis, and DNA analysis revealed that he also had the Glu526Val mutation. He underwent a combined liver and kidney transplant in September of 1995.

Six and a half years after the transplant he has stable kidney function (serum creatinine = 1.8 mg/dL) and most of his prior health issues have been resolved. Kidney biopsies of the transplanted kidney have not shown amyloid deposits. He did have his spleen removed due to a type of anemia, and there were extensive amyloid deposits in his spleen.

Case 2 is the older brother of Case 1, and he developed proteinuria at age 47. He had an orthotopic kidney transplant in 1994, which means a native kidney was removed and a transplanted kidney put in its place. The native kidney did have amyloid deposits. The transplanted kidney had to be removed in April of 1997 due to recurring amyloidosis. His spleen was also removed due to anemia and found to have extensive amyloid deposits. In November of 1999 he underwent a combined liver and kidney transplant. His kidney function has improved (serum creatinine = 1.2 mg/dL), and a kidney biopsy of the transplanted kidney does not show amyloid deposits.


Both of these cases follow a clinical path similar to previous published cases of fibrinogen amyloidosis, in which the patient initially presents with some combination of high blood pressure, proteinuria and elevated serum creatinine which steadily progresses toward kidney failure. It is interesting that both of these patients also had their spleens removed, with both spleens showing extensive amyloid deposits.

With this article we now have a total of three published reports of patients with fibrinogen amyloidosis undergoing combined liver-kidney transplants. You may recall the first article to document such a case was published in 2000, and I reviewed that article on April 30, 2013. That patient underwent a combined liver and kidney transplant in October of 1996. Since the Case 1 patient in this 2003 article underwent a liver and kidney transplant in September of 1995, he was actually the first patient to receive a liver-kidney transplant for fibrinogen amyloidosis.

It is worth noting that all three of these patients were doing well at the time these articles were published, with follow-ups ranging from 2.0 to 6.5 years. Both articles say the results suggest that a liver transplant may be curative for fibrinogen amyloidosis. I believe some upcoming articles will have a few more cases of kidney or liver-kidney transplants, but we will have to wait until a 2009 article before a large number of transplant outcomes are documented.


(1) Zeldenrust S, Gertz M, Uemichi T, et al. Orthotopic liver transplantation for hereditary fibrinogen amyloidosis. Transplantation 2003; 75: 560-561.

Sunday, October 6, 2013

Calcium buttons

This post will have an update on Mom, followed by the always exciting monthly blog statistics at the end. (Two more email subscribers now. Cool.)

In the last update on Mom (Musical Chairs on September 12) there were two main issues. One issue was the difficulty in getting the same tech at the dialysis clinic to finish doing the buttonhole technique on Mom to the point where both access points were complete. I am happy to report that Mom's buttonholes appear to be fully formed now, such that the techs can use the blunt needles and she does not need the Lidocaine to minimize the pain.

The other main issue was Mom's high calcium. At the last update we knew her high calcium was not due to a parathyroid condition, which is the cause in over 95% of the cases. Since then her nephrologist has talked to her internist about it, and the internist had Mom come in for some blood work and a 24-hour urine collection. All of that testing did not turn up anything, so the next step was for Mom to have a bone scan. A bone scan (bone scintigraphy) is where a radioactive material is injected into the patient, and a few hours later a camera that is sensitive to that radiation takes pictures of the patient. The radioactive material is taken up in the bones, and areas of high bone turnover will take up more of the radioactive material. One of the possible causes of high calcium is when a previous cancer has spread (metastasized) to the bone, and Mom does have a history of breast cancer so that would be a possibility.

Mom had the bone scan on Tuesday, October 1. Her nephrologist went over the results with her that Friday and said there does not appear to be any bone cancer. That is definitely good news, but it also means Mom's high calcium is still a mystery. The next thing the nephrologist is going to order is chest, abdominal, and upper leg X-rays (shoulders to knees, basically). I think he may be looking for signs of sarcoidosis, another rare cause of high calcium. If the X-rays do not provide any answers, he said he may order a bone marrow biopsy since multiple myeloma can be a cause of high calcium. Since multiple myeloma is related in many ways to primary (AL) amyloidosis, it would be really bizarre if that turned out to be the cause of her high calcium.

So once again Mom is showing how special she is while her doctors try to determine what is going on.

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

Total posts: 101 (5 in September)

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Total number of countries that have viewed the blog: 74

2 new countries viewed the blog in September:
Czech Republic