Correspondence

Cardiac Amyloidosis with the E526V Mutation of the Fibrinogen A α-Chain

N Engl J Med 2008; 359:2847-2848December 25, 2008

Article

To the Editor:

Proteinuria developed in a 48-year-old man in 2003. His mother had died 10 years earlier from renal amyloidosis. Laboratory tests showed isolated nephrotic-range proteinuria (urinary protein excretion, >7 g per 24 hours) with normal creatinine clearance (estimated glomerular filtration rate with the use of the Modification of Diet in Renal Disease equation, 96 ml per minute per 1.73 m² of body-surface area); no monoclonal gammopathy was found. A specimen from a renal biopsy contained amyloid deposits located exclusively in the mesangium of the glomeruli (Figure 1AFigure 1Amyloid Deposits in Specimens from Renal and Myocardial Biopsies.). The hereditary transmission of the disease led us to perform a molecular analysis for hereditary amyloidosis (associated with transthyretin, fibrinogen, apolipoprotein, or lysozyme); only the E526V mutation of the α-chain of fibrinogen A, the most frequent mutation resulting in fibrinogen amyloidosis, was identified.

Three years later, the patient reported dyspnea (New York Heart Association class II), which gradually increased; 4 years later, a cardiac arrhythmia necessitated implantation of a defibrillator. The patient had no family history of heart disease. Cardiac ultrasonography suggested cardiac amyloidosis, with septal hypertrophy, a left intraventricular gradient of 40 mm Hg, and filling impairment.1 Circumferential thickening of the left ventricle was observed on cardiac magnetic resonance imaging, with focal late-phase contrast enhancement of the posteroseptal territory of the midventricular region. Whereas diffuse enhancement is characteristic of AL amyloidosis,2 focal enhancement suggests non-AL amyloidosis.3 Specimens from multiple myocardial biopsies showed amyloid deposits in subendocardial and perivascular areas (Figure 1B), definitively establishing the diagnosis of cardiac amyloidosis. This amyloid material was specifically labeled with anti-fibrinogen antibodies (Dako F0111), whereas the results of staining with antibodies against λ-chain and κ-chain were negative (Figure 1C).

Since fibrinogen A α-chain amyloidosis was first described in 1993,4 about 40 cases have been reported. Renal involvement is always present, and liver involvement, although rarely observed, has generally resulted in severe disease. Splenic deposits are usually asymptomatic and are frequently observed at autopsy.5

Our report describes cardiac involvement in fibrinogen A α-chain amyloidosis. The hereditary transmission of the disease, the presence of amyloid deposits in specimens from renal and myocardial biopsies, the specific staining with anti-fibrinogen antibody, and the presence of the E526V mutation confirm that our patient had fibrinogen A α-chain amyloidosis with both renal and cardiac involvement. This case shows that fibrinogen A α-chain amyloidosis may involve the heart, leading to life-threatening complications.

Georges Mourad, M.D.
Jean-Philippe Delabre, M.D.
Valérie Garrigue, M.D.
University of Montpellier Medical School, 34295 Montpellier, France
mourad@chu-montpellier.fr

Dr. Mourad reports receiving lecture fees from Novartis, Roche, and Amgen.

No other potential conflict of interest relevant to this letter was reported.

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Citing Articles (4)

Citing Articles

1. 1

   A.V. Kristen, C. Röcken. (2012) Amyloidose des Herzens. Der Pathologe
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2. 2

   A. J. Stangou, N. R. Banner, B. M. Hendry, M. Rela, B. Portmann, J. Wendon, M. Monaghan, P. MacCarthy, M. Buxton-Thomas, C. J. Mathias, J. J. Liepnieks, J. O'Grady, N. D. Heaton, M. D. Benson. (2010) Response: Hereditary fibrinogen A  -chain amyloidosis: phenotypic characterization and the role of liver transplantation. Blood 115:21, 4314-4315
   CrossRef

3. 3

   A. J. Stangou, N. R. Banner, B. M. Hendry, M. Rela, B. Portmann, J. Wendon, M. Monaghan, P. MacCarthy, M. Buxton-Thomas, C. J. Mathias, J. J. Liepnieks, J. O'Grady, N. D. Heaton, M. D. Benson. (2010) Hereditary fibrinogen A  -chain amyloidosis: phenotypic characterization of a systemic disease and the role of liver transplantation. Blood 115:15, 2998-3007
   CrossRef

4. 4

   Rodney H. Falk, Simon W. Dubrey. (2010) Amyloid Heart Disease. Progress in Cardiovascular Diseases 52:4, 347-361
   CrossRef