China
Africa
Explore chapters and articles related to this topic
Mechanisms of Fibril Formation and Cellular Response
Published in Martha Skinner, John L. Berk, Lawreen H. Connors, David C. Seldin, XIth International Symposium on Amyloidosis, 2007
Martha Skinner, John L. Berk, Lawreen H. Connors, David C. Seldin
In hereditary amyloidoses, the greatest clinical experience has been gained in patients with transthyretin amyloidosis. Almost 1250 orthotopic liver transplantations (OLT) have been performed world-wide and most patients have benefited (4). Unfortunately, in patients who had amyloid deposits in the heart before liver transplantation, amyloid deposition continues from wild-type transthyretin (5). Only a few patients with
Incidence of Transthyretin VAL122ILE Amyloid Mutation in African-Americans Born in Indianapolis, Indiana, USA
Published in Gilles Grateau, Robert A. Kyle, Martha Skinner, Amyloid and Amyloidosis, 2004
M.D. Benson, M. Yazaki, T. Yamashita, K. Hamidi Asl
Hereditary transthyretin amyloidosis is associated with greater than 80 different mutations in transthyretin. While the most common type of transthyretin amyloidosis in the world (Val30Met) is found in large pedigrees in Northern Portugal, Northern Sweden, Japan, and smaller families in United States, Europe, and Australia, one particular TTR mutation (Val122Ile) is found predominantly in Americans of African descent (1–3). This mutation causes late-onset restrictive cardiomyopathy (after age 60). In previous reports allele frequencies of 0.014 (148 subjects) and 0.020 (1,688 subjects) were found (4,5). Those studies, however, used DNA samples obtained for genetic analysis of other diseases in various geographic areas. The present study determines the gene frequency in newborns in a mid-American city (Indianapolis, Indiana).
A special case of hypertrophic cardiomyopathy with a differential diagnosis of isolated cardiac amyloidosis or junctophilin type 2 associated cardiomyopathy
Published in Acta Clinica Belgica, 2021
Sévérine De Bruijn, Xavier Galloo, Gilles De Keulenaer, Edgard A. Prihadi, Christiane Brands, Mark Helbert
In ATTR, the hepatic transport protein TTR, previously called prealbumin, is misfolded into an amyloid protein. TTR-related CA accounts for 18% of all cases of CA and is characterised by a progressive infiltrative cardiomyopathy that mimics hypertensive hypertrophic heart disease [7]. Transthyretin amyloidosis encompasses two subtypes. The hereditary/familial type (mATTR) – also called mutant type – arises from misfolding a mutated TTR precursor protein. It is characterized by autosomal dominant inheritance with variable penetrance. In sporadic or wild type (wtATTR), formally also known as senile systemic amyloidosis (SSA), amyloid arises from genetically unaltered TTR [9]. In contrast to AL amyloidosis, mATTR and wtATTR are typically associated with milder clinical manifestations, slower progression, and hence also better prognosis. Since the very slow progression (an 86-your-old patient) and mild clinical presentation (general fatigue with only mild decreased systolic function and no overt clinical heart decompensation) the differential diagnosis of an AL amyloidosis is very improbable based on anamnesis and physical exam. Further work-up confirmed normal immunoglobulin light chains. Arguments in favour of an ATTR are elderly patient, male, slow progression and mild clinical symptoms. As the patient described above only presents cardiac manifestations without altered kidney or liver function, the preferred differential diagnosis of wtATTR is withheld over mATTR.
Advances in pharmacotherapy for cardiac amyloidosis
Published in Expert Opinion on Pharmacotherapy, 2021
R. Spoladore, G. Falasconi, M. Marcatti, S. Di Maio, G. Fiore, M. Slavich, A. Margonato, A. Turco, G. Fragasso
Common treatments for transthyretin wild-type amyloidosis (ATTRwt) were traditionally limited to symptomatic relief; on the other hand orthotopic liver transplantation was normally reserved for specific treatment of the genetic variant of transthyretin amyloidosis (ATTRv) patients, in order to replace the source of vTTR with a new organ able to produce normally conformed transthyretin [55]. Orthotopic liver transplant reduces serum vTTR and improves survival [56]. However, pretransplant symptoms usually last and amyloidotic cardiomyopathy, the most important determinant of mortality, continues to progress [55,56]. For these reasons there is a critical need for new effective, and potentially less invasive, therapeutic options. Nowadays, different new Figure 1drugs have been developed. Some of them can interfere potentially with amyloidogenic wild-type and mutated transthyretin production, others can reduce the following fibrils formation at different stages of disease. These new drugs include transthyretin tetramer stabilizers (diflunisal, tafamidis, epigallocatechin-3-gallate), tranthyretin silencers (patisiran, inotersen), and molecules known as fibril disruptors that could be used both in patients with ATTR amyloidosis and AL amyloidosis (doxycycline, monoclonal antibodies, and tauroursodeoxycholic acid) (Figure 2).
APOE polymorphism in ATTR amyloidosis patients treated with lipid nanoparticle siRNA
Published in Amyloid, 2020
Christoph Niemietz, Oksana Nadzemova, Andree Zibert, Hartmut H.-J. Schmidt
Hereditary transthyretin amyloidosis (ATTR amyloidosis) is a rare, progressive disease resulting from mutation in the transthyretin gene (TTR). Mutation of TTR results in conformational changes of serum TTR affecting protein stability. The amino acid sequence of TTR is primarily expressed by hepatocytes (>95%). TTR encodes a highly conserved protein functioning as a transporter of thyroxine (T4) and vitamin A bound to the retinol-binding protein (RBP). More than 100 amyloidogenic mutations of TTR have been described that cause aggregation and amyloid fibril tissue deposition [1]. Clinical presentation of ATTR amyloidosis is diverse and commonly characterised by neurologic and/or cardiac symptoms [2]. After onset of disease, ATTR amyloidosis is associated with premature death ranging from 3 to 10 years.