Saturday, April 26, 2014

Article Review (2012) - Renal amyloidosis associated with a novel fibrinogen A alpha chain (Afib) mutation

Today's article under review brings us to the year 2012, and it is the first of two abstracts I will be reviewing from the 2012 XIIIth International Symposium on Amyloidosis. The 2012 symposium was held in May of 2012 in Groningen, The Netherlands, which was also the site of the first International Symposium on Amyloidosis in 1967. These symposia are now held every two years, which means there should be one in 2014. And as some of you know, it is being held April 27 through May 1 in Indianapolis, Indiana, hosted by our very own Dr. Merrill Benson. Here is the link to the web site for this year's symposium:

Wow, I just discovered the symposium book is available to download from that site (go to the Program page), and it seems to have all of the abstracts that will be presented. The word "fibrinogen" is in there at least 14 times, so there might be some interesting abstracts for those of you who want to read ahead. I will likely be reviewing one or more of those articles in the blog in a couple of months. Ok, back to today's abstract . . .

Title: Renal amyloidosis associated with a novel fibrinogen A alpha chain (Afib) mutation

Authors: Yvonne A. Efebera, Dorota Rowczenio, Anjali Satoskar, Don M. Menson, Tobor Nadasdy, Philip N. Hawkins (The Ohio State University; National Amyloidosis Centre, London, UK)

Here is the link to a PDF file with all of the abstracts for the 2012 symposium, if you would like to follow along. This abstract is on pages 413 and 414:

This abstract describes the case of a man diagnosed with mild renal insufficiency in 1998 and mild proteinuria in 2005. In October of 2011, at the age of 80, his kidney problems had worsened to the point where his serum creatinine was 5.95 mg/dl and proteinuria was 6379 mg/day. He had no other significant symptoms, and his past medical history included high blood pressure and high cholesterol, both of which were under control. He had no family history of renal disease. His parents were Russian and died at age 72 and 75.

A kidney biopsy showed amyloid deposits in the glomeruli that stained strongly for fibrinogen, and DNA analysis showed this patient had a previously unreported fibrinogen mutation. This mutation was also at position 526, like the most common fibrinogen amyloidosis mutation, Glu526Val. But instead of substituting Valine for Glutamic acid, this mutation substituted Lysine for Glutamic acid. So this mutation would be written as Glu526Lys (or E526K instead of E526V). (For the uber-curious readers: The GAG for Glutamic Acid was changed to AAG for Lysine in this mutation.)

The abstract states that the clinical presentation for this patient was indistinguishable from that of a patient with the Glu526Val mutation, and the amyloid deposition in the biopsy was similar. One major difference between the two mutations is that this patient is of Russian ancestry, whereas the majority of patients with the Glu526Val mutation are of European ancestry.


This mutation is the first new one reported in the literature since the 2009 article by Gillmore, et al (the study of 71 patients) reported on four new mutations. It is interesting that this mutation occurs at the same point as the Glu526Val mutation. As stated in the article, the symptoms of this patient were the same as what we would expect in a patient with the Glu526Val mutation. The symptoms did appear later in life and progress more slowly than we typically see in patients with the Glu526Val mutation, but we cannot draw any conclusions from a single case.

The article did not state whether or not this patient had any offspring, and it did not mention any other relatives. It will be interesting to see if this mutation appears again in the literature, either in this same kindred or a different one.

Next up for review is another abstract from the 2012 symposium which revisits the topic of organ transplants.

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