Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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Effective treatments for mutated transthyretin (TTR)-related cardiac amyloidosis are limited. Heart transplantation or combined liver-heart transplantation are the most successful options, although results rely on underline mechanism and systemic nature of the disease. In this report, we present the first case of a Caucasian patient with the p. ⋯ Val122Ile mutated TTR-related cardiac amyloidosis have been reported. The patient and some members of his family also had mild peripheral neuropathy suggesting a regional phenotypic heterogeneity of European Caucasian TTR p. Val122Ile.
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Gastrointestinal symptoms are frequent in familial amyloid polyneuropathy, mainly resulting from autonomic nervous system involvement. Dysphagia is one of the possible symptoms, although rarely severe or sudden. We describe a case of a sudden onset and severe dysphagia, a rare form of presentation, in a patient whose polyneuropathy was still beeing investigated and turned out to be ATTRVal30Met-polyneuropathy.
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Transthyretin familial amyloid polyneuropathy is characterized by a devastating sensory-motor polyneuropathy associated with life-threatening autonomic disturbance. An early diagnosis is mandatory to increase the chance to modify the course of the disease. This paper underlines the diagnostic problems encountered in this condition.
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Amyloidoses are characterized by the presence of extracellular amyloid deposits, constituted by fibrillar aggregates of misfolded proteins. Despite the similar morphologic appearance of fibrils, at least 28 different proteins have been detected as causative agents of human amyloidoses, 14 of which associated with systemic forms. Unequivocal typing of the amyloid deposits is a key step in the management of these diseases. ⋯ Proteomics indicates the comprehensive study of the proteins in a biological sample, centered on analysis by mass spectrometry. The great potential of this approach in describing the composition of amyloid deposits and in studying the molecular features of the amyloidogenic precursors has become immediately clear and the introduction of proteomics in the clinical practice has revolutionized the field of amyloid typing. This review provides a critical overview of the various approaches that have been proposed in this specific context, along with a brief description of the proteomic methods for assessment of the circulating amyloidogenic proteins.
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We report here a unique amyloidoma of the radial nerve which could not be subtyped by available techniques, including immunohistochemistry and standard clinical and laboratory evaluation. In order to identify the amyloid monomer, we developed a novel preparative procedure designed to optimize conditions for liquid chromatography tandem mass spectrometry analysis of formalin-fixed/paraffin-embedded (FFPE) tissue. Subsequent mass spectrometric analysis clearly identified kappa light chain as the monomer, with no evidence of lambda light chain. ⋯ This study also enabled detailed characterisation of twelve likely amyloid matrix components. Finally, our analysis revealed extensive hydroxylation of collagen type I but, unexpectedly, an almost complete lack of hydroxylated residues in the normally heavily-hydroxylated collagen type VI chains, pointing to structural/functional alterations of collagen VI in this matrix that could have contributed to the pathogenesis of this very unusual tumour. Given the high quality of the data here acquired using a standard quadrupole-time of flight tandem mass spectrometer of modest performance, the robust and straightforward preparative method described constitutes a competitive alternative to more involved approaches using state-of-the-art equipment.