Amyloid fibril composition is related to the phenotype of hereditary transthyretin V30M amyloidosis
- 14 July 2008
- journal article
- research article
- Published by Wiley in The Journal of Pathology
- Vol. 216 (2), 253-261
- https://doi.org/10.1002/path.2411
Abstract
Swedish familial systemic amyloidosis with polyneuropathy (FAP) depends on a mutation leading to a methionine‐for‐valine substitution in transthyretin. The disease appears with different clinical manifestations, including age of onset and involvement of the heart. Liver transplantation is currently the only curative treatment, but progressive cardiomyopathy may occur post‐transplant. Two amyloid deposition patterns have previously been described in the heart. In one, the amyloid consists partially of transthyretin fragments and is weakly stainable by Congo red, while in the other, only full‐length molecules are found and the fibrils have a strong affinity for Congo red. The present study aimed to see whether these morphological and biochemical variations have clinical implications. Subcutaneous adipose tissue biopsies were taken from 33 patients with Val30Met FAP and examined by microscopy, electrophoresis and western blot. Clinical data included age, sex, duration of disease and echocardiographic determination of the interventricular septum (IVS) thickness. It was found that fibrils composed of only full‐length transthyretin were associated with early age of onset (44.8 ± 12.9 years), no clinical cardiac involvement and a strong affinity for Congo red. In contrast, presence of transthyretin fragments in the amyloid was associated with late age of onset (67.3 ± 7.0 years), signs of cardiac involvement and weak Congo red staining. For each individual, the same molecular type of amyloid was found in different organs. This is the first report showing that variations in clinical appearance of familial ATTR amyloidosis are associated with specific structural differences in the amyloid fibrils, and therefore may have a molecular cause. The molecular type of amyloid can be determined from a subcutaneous fat tissue biopsy. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Keywords
This publication has 38 references indexed in Scilit:
- Detailed Structural Analysis of Amyloidogenic Wild-Type Transthyretin Using a Novel Purification Strategy and Mass SpectrometryAnalytical Chemistry, 2007
- Biochemical characterization of vitreous and cardiac amyloid in Ile84Ser transthyretin amyloidosisAmyloid, 2006
- Liver Transplantation Does Not Prevent the Development of Life-Threatening Arrhythmia in Familial Amyloidotic Polyneuropathy, Portuguese-Type (ATTR Val30Met) PatientsTransplantation, 2004
- Tabulation of human transthyretin (TTR) variants, 2003Amyloid, 2003
- Cardiac Amyloid in Patients with Familial Amyloid Polyneuropathy Consists of Abundant Wild-Type TransthyretinBiochemical and Biophysical Research Communications, 2000
- Change in Variant Transthyretin Levels in Patients with Familial Amyloidotic Polyneuropathy Type I Following Liver TransplantationBiochemical and Biophysical Research Communications, 1995
- Purification and Characterization of Amyloid-Related Transthyretin Associated with Familial Amyloidotic CardiomyopathyJBIC Journal of Biological Inorganic Chemistry, 1995
- Purification and Characterization of Amyloid‐Related Transthyretin Associated with Familial Amyloidotic CardiomyopathyJBIC Journal of Biological Inorganic Chemistry, 1995
- Prealbumin in Swedish Patients with Senile Systemic Amyloidosis and Familial Amyloidotic PolyneuropathyScandinavian Journal of Immunology, 1985
- Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements.Circulation, 1978